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David M. Herrington - One of the best experts on this subject based on the ideXlab platform.
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effects of conjugated oestrogen and droloxifene on the renin angiotensin system blood pressure and renal blood flow in postmenopausal women
Clinical Endocrinology, 2004Co-Authors: Ellen W Seely, Gordon H. Williams, Kyoko Okamura, Bridget K Brosnihan, Xavier Jeunemaitre, David M. HerringtonAbstract:OBJECTIVE:The aim of this study was to evaluate the effect of conjugated equine oestrogen (CEE), and droloxifene, a selective oestrogen receptor modulator (SERM) on individual components of renin-angiotensin-aldosterone (RAAS) and blood pressure (BP) in postmenopausal women. DESIGN AND PATIENTS:Twenty-one normotensive (NT) and 10 hypertensive (HT) postmenopausal women received either CEE (0.625 mg/day) or droloxifene (60 mg/day) for 6 weeks and, after a 4-week washout, were restudied on the alternate medication. MEASUREMENTS:Hormones of the RAAS and supine BP were measured prior to and at the end of each drug treatment in all subjects. In a subgroup of the NT (n = 10), 24 h ambulatory BP was performed and renal blood flow was determined by PAH Clearance both basally and in response to 45-min angiotensin II (Ang II) infusion (3 ng/kg/min). RESULTS:CEE significantly increased angiotensinogen, decreased active renin and angiotensin-converting enzyme (ACE), and maintained plasma immunoreactive (ir) angiotensin I (Ang I) levels compared to baseline. With droloxifene, angiotensinogen, active renin and Ang I remained unchanged. Both CEE and droloxifene significantly increased plasma ir-Ang II levels (pmol/l) in NT (baseline: 25.7 +/- 2.5, CEE: 36.6 +/- 3.4, droloxifene: 33.3 +/- 3.1, P < 0.002) and HT women (baseline: 17.9 +/- 2.3, CEE: 27.9 +/- 3.2, droloxifene: 25.9 +/- 4.9, P < 0.005). Renal blood flow was lower on CEE (P = 0.02) compared with baseline. Systemic BP (supine and 24-h ambulatory) was unchanged during both treatments. CONCLUSION:This study demonstrates higher circulating levels of ir-Ang II with CEE and droloxifene.
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effects of conjugated oestrogen and droloxifene on the renin angiotensin system blood pressure and renal blood flow in postmenopausal women
Clinical Endocrinology, 2004Co-Authors: Ellen W Seely, Gordon H. Williams, Kyoko Okamura, Bridget K Brosnihan, Xavier Jeunemaitre, Norman K Hollenberg, David M. HerringtonAbstract:OBJECTIVE:The aim of this study was to evaluate the effect of conjugated equine oestrogen (CEE), and droloxifene, a selective oestrogen receptor modulator (SERM) on individual components of renin-angiotensin-aldosterone (RAAS) and blood pressure (BP) in postmenopausal women. DESIGN AND PATIENTS:Twenty-one normotensive (NT) and 10 hypertensive (HT) postmenopausal women received either CEE (0.625 mg/day) or droloxifene (60 mg/day) for 6 weeks and, after a 4-week washout, were restudied on the alternate medication. MEASUREMENTS:Hormones of the RAAS and supine BP were measured prior to and at the end of each drug treatment in all subjects. In a subgroup of the NT (n = 10), 24 h ambulatory BP was performed and renal blood flow was determined by PAH Clearance both basally and in response to 45-min angiotensin II (Ang II) infusion (3 ng/kg/min). RESULTS:CEE significantly increased angiotensinogen, decreased active renin and angiotensin-converting enzyme (ACE), and maintained plasma immunoreactive (ir) angiotensin I (Ang I) levels compared to baseline. With droloxifene, angiotensinogen, active renin and Ang I remained unchanged. Both CEE and droloxifene significantly increased plasma ir-Ang II levels (pmol/l) in NT (baseline: 25.7 +/- 2.5, CEE: 36.6 +/- 3.4, droloxifene: 33.3 +/- 3.1, P < 0.002) and HT women (baseline: 17.9 +/- 2.3, CEE: 27.9 +/- 3.2, droloxifene: 25.9 +/- 4.9, P < 0.005). Renal blood flow was lower on CEE (P = 0.02) compared with baseline. Systemic BP (supine and 24-h ambulatory) was unchanged during both treatments. CONCLUSION:This study demonstrates higher circulating levels of ir-Ang II with CEE and droloxifene.
Gordon H. Williams - One of the best experts on this subject based on the ideXlab platform.
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Non-Modulation as an Intermediate Phenotype in Essential Hypertension
2016Co-Authors: Gordon H. Williams, Paul N Hopkins, Robert G. Dluhy, Richard P. Iifton, Thomas J. Moore, Ray Gleason, Roger Williams, Steven C. Hunt, Norman K HollenbergAbstract:Non-modulation is a trait characterized by abnormal angiotensin-mediated control of aldosterone release and the renal blood supply. To determine whether non-modulation defines a specific subgroup of the hypertensive population and its utility as an intermediate phenotype, we have studied the distribution of this quantitative trait, whether its features are reproducible on repeated testing, and whether there is concordance of its multiple features. Essential hypertensive patients (224) and nonnotensive subjects (119) received an infusion of angiotensin II (Ang II) at 3 ng • kg'1 • min"1 for 30-45 minutes. p-Aminohippurate (PAH) Clearance was assessed as an index of renal plasma flow while the subjects were on a 200 meq sodium diet; plasma aldosterone levels were measured while the subjects were on a 10 meq sodium diet In 54 subjects, diuretic-induced volume depletion superimposed on a low salt diet was substituted for the Ang II infusion. The results of each study were submitted to maximum likelihood analysis to assess bimodality. In response to both diuretic-Induced volume depletion (/><0.000023) and Ang II infusion (p<0.0009), aldosterone responses were bimodally distributed in the essential hyperten-sive bat not in the nonnotensive subjects, suggesting that this trait identifies a discrete subgroup. In the 59 subjects who had both an adrenal and renal study, 50 (85%) were concordant. Finally, in 27 subjects studied two to sis times ovsr a span of 1-60 months, the intraclass correlations of the adrenal, PAH, o
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uric acid and the state of the intrarenal renin angiotensin system in humans
Kidney International, 2004Co-Authors: Todd S Perlstein, Gordon H. Williams, Olga Gumieniak, Paul N Hopkins, Laine J Murphey, Nancy J Brown, Norman K Hollenberg, Naomi D L FisherAbstract:Uric acid and the state of the intrarenal renin-angiotensin system in humans. Background Experimental hyperuricemia is marked by an activated intrarenal renin-angiotensin system (RAS). The renal vascular response to exogenous angiotensin II (Ang II) provides an indirect measure of intrarenal RAS activity. We tested the hypothesis that the serum uric acid concentration predicts the renal vascular response to Ang II. Methods A total of 249 subjects in high sodium balance had the renal plasma flow (RPF) response to Ang II measured. Para-aminohippuric acid (PAH) Clearance was used to estimate RPF. Multivariable regression analysis determined if the serum uric acid concentration independently predicts the RPF response to Ang II. Variables considered included age, gender, race, body mass index (BMI), hypertension status, blood pressure, basal RPF, creatinine Clearance, serum insulin, serum glucose, serum high-density lipoprotein (HDL), serum triglycerides, and plasma renin activity (PRA). Results Uric acid concentration negatively correlated with the RPF response to Ang II ( r =-0.37, P P Conclusion Serum uric acid independently predicted blunted renal vascular responsiveness to Ang II, consistent with results from experimental hyperuricemia showing an activated intrarenal RAS. This could be due to a direct effect of uric acid or reflect a more fundamental renal process. These data may have relevance to the association of uric acid with risk for hypertension and nephropathy.
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effects of conjugated oestrogen and droloxifene on the renin angiotensin system blood pressure and renal blood flow in postmenopausal women
Clinical Endocrinology, 2004Co-Authors: Ellen W Seely, Gordon H. Williams, Kyoko Okamura, Bridget K Brosnihan, Xavier Jeunemaitre, David M. HerringtonAbstract:OBJECTIVE:The aim of this study was to evaluate the effect of conjugated equine oestrogen (CEE), and droloxifene, a selective oestrogen receptor modulator (SERM) on individual components of renin-angiotensin-aldosterone (RAAS) and blood pressure (BP) in postmenopausal women. DESIGN AND PATIENTS:Twenty-one normotensive (NT) and 10 hypertensive (HT) postmenopausal women received either CEE (0.625 mg/day) or droloxifene (60 mg/day) for 6 weeks and, after a 4-week washout, were restudied on the alternate medication. MEASUREMENTS:Hormones of the RAAS and supine BP were measured prior to and at the end of each drug treatment in all subjects. In a subgroup of the NT (n = 10), 24 h ambulatory BP was performed and renal blood flow was determined by PAH Clearance both basally and in response to 45-min angiotensin II (Ang II) infusion (3 ng/kg/min). RESULTS:CEE significantly increased angiotensinogen, decreased active renin and angiotensin-converting enzyme (ACE), and maintained plasma immunoreactive (ir) angiotensin I (Ang I) levels compared to baseline. With droloxifene, angiotensinogen, active renin and Ang I remained unchanged. Both CEE and droloxifene significantly increased plasma ir-Ang II levels (pmol/l) in NT (baseline: 25.7 +/- 2.5, CEE: 36.6 +/- 3.4, droloxifene: 33.3 +/- 3.1, P < 0.002) and HT women (baseline: 17.9 +/- 2.3, CEE: 27.9 +/- 3.2, droloxifene: 25.9 +/- 4.9, P < 0.005). Renal blood flow was lower on CEE (P = 0.02) compared with baseline. Systemic BP (supine and 24-h ambulatory) was unchanged during both treatments. CONCLUSION:This study demonstrates higher circulating levels of ir-Ang II with CEE and droloxifene.
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effects of conjugated oestrogen and droloxifene on the renin angiotensin system blood pressure and renal blood flow in postmenopausal women
Clinical Endocrinology, 2004Co-Authors: Ellen W Seely, Gordon H. Williams, Kyoko Okamura, Bridget K Brosnihan, Xavier Jeunemaitre, Norman K Hollenberg, David M. HerringtonAbstract:OBJECTIVE:The aim of this study was to evaluate the effect of conjugated equine oestrogen (CEE), and droloxifene, a selective oestrogen receptor modulator (SERM) on individual components of renin-angiotensin-aldosterone (RAAS) and blood pressure (BP) in postmenopausal women. DESIGN AND PATIENTS:Twenty-one normotensive (NT) and 10 hypertensive (HT) postmenopausal women received either CEE (0.625 mg/day) or droloxifene (60 mg/day) for 6 weeks and, after a 4-week washout, were restudied on the alternate medication. MEASUREMENTS:Hormones of the RAAS and supine BP were measured prior to and at the end of each drug treatment in all subjects. In a subgroup of the NT (n = 10), 24 h ambulatory BP was performed and renal blood flow was determined by PAH Clearance both basally and in response to 45-min angiotensin II (Ang II) infusion (3 ng/kg/min). RESULTS:CEE significantly increased angiotensinogen, decreased active renin and angiotensin-converting enzyme (ACE), and maintained plasma immunoreactive (ir) angiotensin I (Ang I) levels compared to baseline. With droloxifene, angiotensinogen, active renin and Ang I remained unchanged. Both CEE and droloxifene significantly increased plasma ir-Ang II levels (pmol/l) in NT (baseline: 25.7 +/- 2.5, CEE: 36.6 +/- 3.4, droloxifene: 33.3 +/- 3.1, P < 0.002) and HT women (baseline: 17.9 +/- 2.3, CEE: 27.9 +/- 3.2, droloxifene: 25.9 +/- 4.9, P < 0.005). Renal blood flow was lower on CEE (P = 0.02) compared with baseline. Systemic BP (supine and 24-h ambulatory) was unchanged during both treatments. CONCLUSION:This study demonstrates higher circulating levels of ir-Ang II with CEE and droloxifene.
Reinhard Schneider - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of kidney function with serum parameters in vivo after 24 h.
2015Co-Authors: Martin Alexander Schick, Wolfgang Baar, Raphael Romano Bruno, Jakob Wollborn, Christopher Held, Reinhard Schneider, Sven Flemming, Nicolas Schlegel, Norbert Roewer, Winfried NeuhausAbstract:A: Inulin-Clearance [ml/min], the gold standard of kindey function; B: PAH-Clearance [ml/min]; C: NGAL [pg/ml]; D: Cystatin C [pg/ml]; E: Creatinine [mg/dl] F: Urea [mg/dl], n = 6, * p
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Schematic presentation of the experimental setup.
2015Co-Authors: Martin Alexander Schick, Wolfgang Baar, Raphael Romano Bruno, Jakob Wollborn, Christopher Held, Reinhard Schneider, Sven Flemming, Nicolas Schlegel, Norbert Roewer, Winfried NeuhausAbstract:At point of time 0 h after cannulation of the right jugular vein and the left carotid artery, sham or sCASP procedure was performed. Baseline measurements of macrohemodynamic and blood gas analysis followed after operation. 18 hours after operation, sCASP+VOL and Control+VOL received 50 ml/kg/BW 6% HES 130/0.4 (VOL) within the following 6 hours. Twenty-four hours after first operation, macrohaemodynamics and blood gas parameters were measured, and renal function was analysed by inulin- and PAH- Clearance. At the end of experiment blood serum, blood gas analysis and kidney were harvested.
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sepsis induced acute kidney injury by standardized colon ascendens stent peritonitis in rats a simple reproducible animal model
Intensive Care Medicine Experimental, 2014Co-Authors: Martin A Schick, Wolfgang Baar, Jakob Wollborn, Christopher Held, Reinhard Schneider, Sven Flemming, Nicolas Schlegel, Robert W Brock, Norbert RoewerAbstract:Up to 50% of septic patients develop acute kidney injury (AKI). The pathomechanism of septic AKI is poorly understood. Therefore, we established an innovative rodent model to characterize sepsis-induced AKI by standardized colon ascendens stent peritonitis (sCASP). The model has a standardized focus of infection, an intensive care set up with monitoring of haemodynamics and oxygenation resulting in predictable impairment of renal function, AKI parameters as well as histopathology scoring. Anaesthetized rats underwent the sCASP procedure, whereas sham animals were sham operated and control animals were just monitored invasively. Haemodynamic variables and blood gases were continuously measured. After 24 h, animals were reanesthetized; cardiac output (CO), inulin and PAH Clearances were measured and later on kidneys were harvested; and creatinine, urea, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) were analysed. Additional sCASP-treated animals were investigated after 3 and 9 days. All sCASP-treated animals survived, whilst ubiquitous peritonitis and significantly deteriorated clinical and macrohaemodynamic sepsis signs after 24 h (MAP, CO, heart rate) were obvious. Blood analyses showed increased lactate and IL-6 levels as well as leucopenia. Urine output, inulin and PAH Clearance were significantly decreased in sCASP compared to sham and control. Additionally, significant increase in cystatin C and NGAL was detected. Standard parameters like serum creatinine and urea were elevated and sCASP-induced sepsis increased significantly in a time-dependent manner. The renal histopathological score of sCASP-treated animals deteriorated after 3 and 9 days. The presented sCASP method is a standardized, reliable and reproducible method to induce septic AKI. The intensive care set up, continuous macrohaemodynamic and gas exchange monitoring, low mortality rate as well as the opportunity of detailed analyses of kidney function and impairments are advantages of this setup. Thus, our described method may serve as a new standard for experimental investigations of septic AKI.
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Sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model
Intensive Care Medicine Experimental, 2014Co-Authors: Martin A Schick, Wolfgang Baar, Jakob Wollborn, Christopher Held, Reinhard Schneider, Sven Flemming, Nicolas Schlegel, Norbert Roewer, Robert W Brock, Christian WunderAbstract:Background Up to 50% of septic patients develop acute kidney injury (AKI). The pathomechanism of septic AKI is poorly understood. Therefore, we established an innovative rodent model to characterize sepsis-induced AKI by standardized colon ascendens stent peritonitis (sCASP). The model has a standardized focus of infection, an intensive care set up with monitoring of haemodynamics and oxygenation resulting in predictable impairment of renal function, AKI parameters as well as histopathology scoring. Methods Anaesthetized rats underwent the sCASP procedure, whereas sham animals were sham operated and control animals were just monitored invasively. Haemodynamic variables and blood gases were continuously measured. After 24 h, animals were reanesthetized; cardiac output (CO), inulin and PAH Clearances were measured and later on kidneys were harvested; and creatinine, urea, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) were analysed. Additional sCASP-treated animals were investigated after 3 and 9 days. Results All sCASP-treated animals survived, whilst ubiquitous peritonitis and significantly deteriorated clinical and macrohaemodynamic sepsis signs after 24 h (MAP, CO, heart rate) were obvious. Blood analyses showed increased lactate and IL-6 levels as well as leucopenia. Urine output, inulin and PAH Clearance were significantly decreased in sCASP compared to sham and control. Additionally, significant increase in cystatin C and NGAL was detected. Standard parameters like serum creatinine and urea were elevated and sCASP-induced sepsis increased significantly in a time-dependent manner. The renal histopathological score of sCASP-treated animals deteriorated after 3 and 9 days. Conclusions The presented sCASP method is a standardized, reliable and reproducible method to induce septic AKI. The intensive care set up, continuous macrohaemodynamic and gas exchange monitoring, low mortality rate as well as the opportunity of detailed analyses of kidney function and impairments are advantages of this setup. Thus, our described method may serve as a new standard for experimental investigations of septic AKI.
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increased symmetrical dimethylarginine in ischemic acute kidney injury as a causative factor of renal l arginine deficiency
Translational Research, 2013Co-Authors: Boris Betz, Christoph Sauvant, Kerstin Mollerehrlich, Tobias Kress, Joachim Kniepert, Edzard Schwedhelm, Rainer H Boger, Christoph Wanner, Reinhard SchneiderAbstract:Availability of L-arginine, the exclusive substrate for nitric oxide synthases, plays an important role in kidney ischemia/reperfusion injury. The endogenous L-arginine derivatives asymmetrical dimethylarginine (ADMA) and symmetrical dimethylarginine (SDMA) block cellular L-arginine uptake competitively, thereby inhibiting the production of nitric oxide. ADMA also blocks nitric oxide synthase activity directly. Here, we investigate the pathomechanistic impact of ADMA and SDMA on ischemic acute kidney injury. Rats were subject to bilateral renal ischemia (60 minutes)/reperfusion (24 hours) injury. Impairment of renal function was determined with inulin Clearance (glomerular filtration rate) and para-aminohippurate (PAH) Clearance (renal plasma flow). L-arginine, ADMA, and SDMA levels were measured by liquid chromatography–tandem mass spectrometry. L-arginine was extracted from renal tissue and analyzed by enzyme-linked immunosorbent assay, and protein and messenger RNA expressions were determined by Western blot and real-time reverse transcription polymerase chain reaction. Renal function deteriorated severely after ischemia/reperfusion injury, as demonstrated by inulin and PAH Clearance. Serum ADMA and SDMA increased, but tissue expression of specific ADMA or SDMA synthesizing and metabolizing enzymes (protein arginine methyltransferases and dimethyl arginine dimethylaminohydrolases) did not alter. Serum L-arginine increased as well, whereas intracellular L-arginine concentration diminished. Renal messenger RNA expression of cationic amino acid transporters, which mediate L-arginine uptake, remained unchanged. In serum, the ratio of L-arginine to ADMA did not alter after ischemia/reperfusion injury, whereas the ratios of L-arginine to SDMA and ADMA to SDMA decreased. A marked increase in serum SDMA, especially when accompanied by a diminished L-arginine-to-SDMA ratio, might reflect competitive inhibition of cellular L-arginine uptake by SDMA. As a consequence, a pathologic renal L-arginine deficiency in ischemic acute kidney injury results.
Braz, José Reinaldo Cerqueira - One of the best experts on this subject based on the ideXlab platform.
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Efeitos do halotano, isoflurano e sevoflurano sobre a função renal em cães sob pinçamento aórtico infra-renal
Sociedade Brasileira de Anestesiologia, 2003Co-Authors: Bisinotto, Flora Margarida Barra, Braz, José Reinaldo CerqueiraAbstract:JUSTIFICATIVA E OBJETIVOS: O pinçamento infra-renal da aorta abdominal pode produzir alterações renais. O objetivo do estudo foi avaliar os efeitos do halotano, isoflurano e sevoflurano sobre a função renal, em cães submetidos a pinçamento aórtico infra-renal. MÉTODO: O estudo aleatório foi realizado em 30 cães, distribuídos em três grupos, de acordo com o anestésico halogenado utilizado durante a anestesia, em concentrações equipotentes de 0,75 CAM: GH (n = 10) - halotano a 0,67%; GI (n = 10) - isoflurano a 0,96%; e GS (n = 10) - sevoflurano a 1,8%. em todos os animais foi realizada ligadura infra-renal da aorta, por período de 30 minutos. Os atributos renais foram estudados nos momentos: C (controle), após 15 (Ao15) e 30 (Ao30) minutos de pinçamento aórtico, e após 15 (DAo15) e 30 (DAo30) minutos do despinçamento aórtico. RESULTADOS: A depuração de água livre foi menor nos grupos GI e GS, em relação ao GH, após o despinçamento aórtico (p < 0,05). Durante o pinçamento aórtico, nos três grupos, houve aumento do débito urinário, da excreção urinária de sódio e da depuração de sódio, e diminuição da osmolaridade urinária (p < 0,05). A resistência vascular renal e a fração de filtração aumentaram somente em GS (p < 0,05), enquanto a excreção fracionária de sódio aumentou em GH e GI (p < 0,05). Após o despinçamento aórtico, houve normalização dos atributos que haviam se alterado, com exceção da osmolaridade urinária, que continuou em níveis menores do que os do controle em todos os grupos (p < 0,05). A resistência vascular renal e a fração de filtração continuaram mais elevadas em GS, acompanhadas por diminuição do fluxo sangüíneo renal e da depuração de para-aminohipurato de sódio (p < 0,05). CONCLUSÕES: No cão nas condições experimentais empregadas, a inalação de halotano e isoflurano a 0,75 CAM, mas não de sevoflurano, atenuou a principal alteração após o pinçamento infra-renal da aorta, que é o aumento da resistência vascular renal.JUSTIFICATIVA Y OBJETIVOS: El pinzamiento infra-renal de la aorta abdominal puede producir alteraciones renales. La finalidad del estudio fue evaluar los efectos del halotano, isoflurano y sevoflurano sobre la función renal, en canes sometidos a pinzamiento aórtico infra-renal. MÉTODO: El estudio aleatorio fue realizado en 30 canes, distribuidos en tres grupos, de acuerdo con el anestésico halogenado utilizado durante la anestesia, en concentraciones equipotentes de 0,75 CAM: GH (n = 10) - halotano a 0,67%; GI (n = 10) - isoflurano a 0,96%; y GS (n = 10) - sevoflurano a 1,8%. En todos los animales fue realizada ligadura infra-renal de la aorta, por un período de 30 minutos. Los atributos renales fueron estudiados en los momentos: C (control), después 15 (Ao15) y 30 (Ao30) minutos de pinzamiento aórtico, y después 15 (DAo15) y 30 (DAo30) minutos del despinzamiento aórtico. RESULTADOS: La depuración de agua libre fue menor en los grupos GI y GS, en relación a la GH, después del despinzamiento aórtico (p < 0,05). Durante el pinzamiento aórtico, en los tres grupos, hubo aumento del débito urinario, de la excreción urinaria de sodio y de la depuración de sodio, y diminución de la osmolaridad urinaria (p < 0,05). La resistencia vascular renal y la fracción de filtración aumentaron solamente en GS (p < 0,05), en cuanto la excreción fraccionaria de sodio aumentó en GH y GI (p < 0,05). Después del despinzamiento aórtico, hubo normalización de los atributos que se habían alterado, con excepción de la osmolaridad urinaria, que continuó en niveles menores que los del control en todos los grupos (p < 0,05). La resistencia vascular renal y la fracción de filtración continuaron más elevadas en GS, acompañadas por diminución del flujo sanguíneo renal y de la depuración de para-aminohipurato de sodio (p < 0,05). CONCLUSIONES: En el can, en las condiciones experimentales empleadas, la inhalación de halotano e isoflurano a 0,75 CAM, más no de sevoflurano, atenuó la principal alteración después del pinzamiento infra-renal de la aorta, que es un aumento de la resistencia vascular renal.BACKGROUND and OBJECTIVES: Infra-renal aortic cross-clamping is associated to renal effects. This study aimed at analyzing halothane, isoflurane and sevoflurane effects on renal function of dogs submitted to infra-renal aortic cross-clamping. METHODS: This study involved 30 mixed-breed dogs randomly distributed in three groups, according to equipotent anesthetic doses (0.75 MAC) of inhaled anesthetics: GH (n = 10) - 0.67% halothane; GI (n = 10) - 0.96% isoflurane; and GS (n = 10) - 1.8% sevoflurane. All animals were submitted to infra-renal aortic cross-clamping for 30 minutes. Renal parameters were evaluated at control (C), 15 (Ao15) and (Ao30) minutes after aortic cross-clamping, and 15 (DAo15) and 30 (DAo30) minutes after aortic unclamping. RESULTS: Free water Clearance was significantly lower in GI and GS as compared to GH (p < 0.05) after aortic unclamping. Urinary output, sodium urinary excretion and sodium Clearance have significantly increased during aortic cross-clamping, while urinary osmolarity has decreased in all groups (p < 0.05). Renal vascular resistance and filtration fraction have increased during aortic cross-clamping in GS only, while sodium fractional excretion increased in GH and GI (p < 0.05). All renal parameters had returned to control levels after aortic unclamping, with the exception of urinary osmolality which has remained below control levels in all groups (p < 0.05). Renal vascular resistance and filtration fraction have remained higher in GS, followed by renal blood flow and PAH Clearance decrease (p < 0.05). CONCLUSIONS: In dogs under our experimental conditions, 0.75 MAC of halothane or isoflurane, but not 0.75 MAC of sevoflurane, have minimized renal vascular resistance increase, which is the major infra-renal aortic cross-clamping effect
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Efectos del halotano, isoflurano y sevoflurano sobre la función renal en canes bajo pinzamiento aórtico infra-renal
Sociedade Brasileira de Anestesiologia, 2003Co-Authors: Bisinotto, Flora Margarida Barra, Braz, José Reinaldo CerqueiraAbstract:JUSTIFICATIVA E OBJETIVOS: O pinçamento infra-renal da aorta abdominal pode produzir alterações renais. O objetivo do estudo foi avaliar os efeitos do halotano, isoflurano e sevoflurano sobre a função renal, em cães submetidos a pinçamento aórtico infra-renal. MÉTODO: O estudo aleatório foi realizado em 30 cães, distribuídos em três grupos, de acordo com o anestésico halogenado utilizado durante a anestesia, em concentrações equipotentes de 0,75 CAM: GH (n = 10) - halotano a 0,67%; GI (n = 10) - isoflurano a 0,96%; e GS (n = 10) - sevoflurano a 1,8%. Em todos os animais foi realizada ligadura infra-renal da aorta, por período de 30 minutos. Os atributos renais foram estudados nos momentos: C (controle), após 15 (Ao15) e 30 (Ao30) minutos de pinçamento aórtico, e após 15 (DAo15) e 30 (DAo30) minutos do despinçamento aórtico. RESULTADOS: A depuração de água livre foi menor nos grupos GI e GS, em relação ao GH, após o despinçamento aórtico (p < 0,05). Durante o pinçamento aórtico, nos três grupos, houve aumento do débito urinário, da excreção urinária de sódio e da depuração de sódio, e diminuição da osmolaridade urinária (p < 0,05). A resistência vascular renal e a fração de filtração aumentaram somente em GS (p < 0,05), enquanto a excreção fracionária de sódio aumentou em GH e GI (p < 0,05). Após o despinçamento aórtico, houve normalização dos atributos que haviam se alterado, com exceção da osmolaridade urinária, que continuou em níveis menores do que os do controle em todos os grupos (p < 0,05). A resistência vascular renal e a fração de filtração continuaram mais elevadas em GS, acompanhadas por diminuição do fluxo sangüíneo renal e da depuração de para-aminohipurato de sódio (p < 0,05). CONCLUSÕES: No cão nas condições experimentais empregadas, a inalação de halotano e isoflurano a 0,75 CAM, mas não de sevoflurano, atenuou a principal alteração após o pinçamento infra-renal da aorta, que é o aumento da resistência vascular renal.BACKGROUND AND OBJECTIVES: Infra-renal aortic cross-clamping is associated to renal effects. This study aimed at analyzing halothane, isoflurane and sevoflurane effects on renal function of dogs submitted to infra-renal aortic cross-clamping. METHODS: This study involved 30 mixed-breed dogs randomly distributed in three groups, according to equipotent anesthetic doses (0.75 MAC) of inhaled anesthetics: GH (n = 10) - 0.67% halothane; GI (n = 10) - 0.96% isoflurane; and GS (n = 10) - 1.8% sevoflurane. All animals were submitted to infra-renal aortic cross-clamping for 30 minutes. Renal parameters were evaluated at control (C), 15 (Ao15) and (Ao30) minutes after aortic cross-clamping, and 15 (DAo15) and 30 (DAo30) minutes after aortic unclamping. RESULTS: Free water Clearance was significantly lower in GI and GS as compared to GH (p < 0.05) after aortic unclamping. Urinary output, sodium urinary excretion and sodium Clearance have significantly increased during aortic cross-clamping, while urinary osmolarity has decreased in all groups (p < 0.05). Renal vascular resistance and filtration fraction have increased during aortic cross-clamping in GS only, while sodium fractional excretion increased in GH and GI (p < 0.05). All renal parameters had returned to control levels after aortic unclamping, with the exception of urinary osmolality which has remained below control levels in all groups (p < 0.05). Renal vascular resistance and filtration fraction have remained higher in GS, followed by renal blood flow and PAH Clearance decrease (p < 0.05). CONCLUSIONS: In dogs under our experimental conditions, 0.75 MAC of halothane or isoflurane, but not 0.75 MAC of sevoflurane, have minimized renal vascular resistance increase, which is the major infra-renal aortic cross-clamping effect.JUSTIFICATIVA Y OBJETIVOS: El pinzamiento infra-renal de la aorta abdominal puede producir alteraciones renales. La finalidad del estudio fue evaluar los efectos del halotano, isoflurano y sevoflurano sobre la función renal, en canes sometidos a pinzamiento aórtico infra-renal. MÉTODO: El estudio aleatorio fue realizado en 30 canes, distribuidos en tres grupos, de acuerdo con el anestésico halogenado utilizado durante la anestesia, en concentraciones equipotentes de 0,75 CAM: GH (n = 10) - halotano a 0,67%; GI (n = 10) - isoflurano a 0,96%; y GS (n = 10) - sevoflurano a 1,8%. En todos los animales fue realizada ligadura infra-renal de la aorta, por un período de 30 minutos. Los atributos renales fueron estudiados en los momentos: C (control), después 15 (Ao15) y 30 (Ao30) minutos de pinzamiento aórtico, y después 15 (DAo15) y 30 (DAo30) minutos del despinzamiento aórtico. RESULTADOS: La depuración de agua libre fue menor en los grupos GI y GS, en relación a la GH, después del despinzamiento aórtico (p < 0,05). Durante el pinzamiento aórtico, en los tres grupos, hubo aumento del débito urinario, de la excreción urinaria de sodio y de la depuración de sodio, y diminución de la osmolaridad urinaria (p < 0,05). La resistencia vascular renal y la fracción de filtración aumentaron solamente en GS (p < 0,05), en cuanto la excreción fraccionaria de sodio aumentó en GH y GI (p < 0,05). Después del despinzamiento aórtico, hubo normalización de los atributos que se habían alterado, con excepción de la osmolaridad urinaria, que continuó en niveles menores que los del control en todos los grupos (p < 0,05). La resistencia vascular renal y la fracción de filtración continuaron más elevadas en GS, acompañadas por diminución del flujo sanguíneo renal y de la depuración de para-aminohipurato de sodio (p < 0,05). CONCLUSIONES: En el can, en las condiciones experimentales empleadas, la inhalación de halotano e isoflurano a 0,75 CAM, más no de sevoflurano, atenuó la principal alteración después del pinzamiento infra-renal de la aorta, que es un aumento de la resistencia vascular renal
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Efeitos do alopurinol em rins isquemicos de caes anestesiados com pentobarbital sodico
2000Co-Authors: Módolo, Norma Sueli Pinheiro, Castiglia, Yara Marcondes Machado, Ganem, Eliana Marisa, Braz, José Reinaldo Cerqueira, Vianna, Pedro Thadeu GalvãoAbstract:Background and Objectives - Allopurinol is a drug which inhibits the formation of noxious renal free radicals. The aim of this study was to evaluate the protecting renal effects of allopurinol in ischemic kidneys of dogs. Methods - Sixteen dogs were anesthetized with sodium pentobarbital and submitted to extracellular volume expansion (1.4 ml.kg-1.min-1), to mechanic ventilation with air, to right nephrectomy and to left renal artery clamping. Changes which might occur in renal morphology and function after 30 min of total ischemia and posterior reperfusion were studied in Group 1 (G1), in addition to the action of allopurinol (50 mg.kg-1) on those kidneys, when administered 24 h before the experiment and 1 h before the ischemic procedure in Group 2 (G2). The following parameters: heart rate, inferior vena cava pressure, mean blood pressure, PAH Clearance (PAH(c)), renal blood flow (RBF), renal vascular resistance (RVR), creatinine Clearance (Cr(c)), filtration fraction, urine output, plasma and urine osmolality, osmolar Clearance, free water, sodium and potassium Clearance, urine and fractional sodium and potassium excretion, hematocrit, rectal temperature, and left kidney histology were evaluated in four moments: M1 control, and M2, M3, M4 obtained immediately, 15 and 30 min after unclamping of the left renal artery. In G2, M1, M2, M3 and M4 were obtained 45, 90, 105, and 120 min after the second allopurinol dose. Results - Both groups showed the highest values for PAH(c), RBF, and Cr(c), and the lowest values for RVR in M1. Animals were tachycardiac since the beginning of the experiment both in G1 and in G2. The other parameters were not changed. Left kidney histological evaluation showed alterations compatible with acute tubular necrosis in both experimental groups. Conclusions - Alterations found in renal hemodynamics were compatible with the release of vasoconstrictor substances due to renal ischemia. Allopurinol was not effective in preventing renal alterations caused by ischemia and reperfusion
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effects of conjugated oestrogen and droloxifene on the renin angiotensin system blood pressure and renal blood flow in postmenopausal women
Clinical Endocrinology, 2004Co-Authors: Ellen W Seely, Gordon H. Williams, Kyoko Okamura, Bridget K Brosnihan, Xavier Jeunemaitre, David M. HerringtonAbstract:OBJECTIVE:The aim of this study was to evaluate the effect of conjugated equine oestrogen (CEE), and droloxifene, a selective oestrogen receptor modulator (SERM) on individual components of renin-angiotensin-aldosterone (RAAS) and blood pressure (BP) in postmenopausal women. DESIGN AND PATIENTS:Twenty-one normotensive (NT) and 10 hypertensive (HT) postmenopausal women received either CEE (0.625 mg/day) or droloxifene (60 mg/day) for 6 weeks and, after a 4-week washout, were restudied on the alternate medication. MEASUREMENTS:Hormones of the RAAS and supine BP were measured prior to and at the end of each drug treatment in all subjects. In a subgroup of the NT (n = 10), 24 h ambulatory BP was performed and renal blood flow was determined by PAH Clearance both basally and in response to 45-min angiotensin II (Ang II) infusion (3 ng/kg/min). RESULTS:CEE significantly increased angiotensinogen, decreased active renin and angiotensin-converting enzyme (ACE), and maintained plasma immunoreactive (ir) angiotensin I (Ang I) levels compared to baseline. With droloxifene, angiotensinogen, active renin and Ang I remained unchanged. Both CEE and droloxifene significantly increased plasma ir-Ang II levels (pmol/l) in NT (baseline: 25.7 +/- 2.5, CEE: 36.6 +/- 3.4, droloxifene: 33.3 +/- 3.1, P < 0.002) and HT women (baseline: 17.9 +/- 2.3, CEE: 27.9 +/- 3.2, droloxifene: 25.9 +/- 4.9, P < 0.005). Renal blood flow was lower on CEE (P = 0.02) compared with baseline. Systemic BP (supine and 24-h ambulatory) was unchanged during both treatments. CONCLUSION:This study demonstrates higher circulating levels of ir-Ang II with CEE and droloxifene.
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effects of conjugated oestrogen and droloxifene on the renin angiotensin system blood pressure and renal blood flow in postmenopausal women
Clinical Endocrinology, 2004Co-Authors: Ellen W Seely, Gordon H. Williams, Kyoko Okamura, Bridget K Brosnihan, Xavier Jeunemaitre, Norman K Hollenberg, David M. HerringtonAbstract:OBJECTIVE:The aim of this study was to evaluate the effect of conjugated equine oestrogen (CEE), and droloxifene, a selective oestrogen receptor modulator (SERM) on individual components of renin-angiotensin-aldosterone (RAAS) and blood pressure (BP) in postmenopausal women. DESIGN AND PATIENTS:Twenty-one normotensive (NT) and 10 hypertensive (HT) postmenopausal women received either CEE (0.625 mg/day) or droloxifene (60 mg/day) for 6 weeks and, after a 4-week washout, were restudied on the alternate medication. MEASUREMENTS:Hormones of the RAAS and supine BP were measured prior to and at the end of each drug treatment in all subjects. In a subgroup of the NT (n = 10), 24 h ambulatory BP was performed and renal blood flow was determined by PAH Clearance both basally and in response to 45-min angiotensin II (Ang II) infusion (3 ng/kg/min). RESULTS:CEE significantly increased angiotensinogen, decreased active renin and angiotensin-converting enzyme (ACE), and maintained plasma immunoreactive (ir) angiotensin I (Ang I) levels compared to baseline. With droloxifene, angiotensinogen, active renin and Ang I remained unchanged. Both CEE and droloxifene significantly increased plasma ir-Ang II levels (pmol/l) in NT (baseline: 25.7 +/- 2.5, CEE: 36.6 +/- 3.4, droloxifene: 33.3 +/- 3.1, P < 0.002) and HT women (baseline: 17.9 +/- 2.3, CEE: 27.9 +/- 3.2, droloxifene: 25.9 +/- 4.9, P < 0.005). Renal blood flow was lower on CEE (P = 0.02) compared with baseline. Systemic BP (supine and 24-h ambulatory) was unchanged during both treatments. CONCLUSION:This study demonstrates higher circulating levels of ir-Ang II with CEE and droloxifene.
