The Experts below are selected from a list of 171 Experts worldwide ranked by ideXlab platform
Edward J. Johns - One of the best experts on this subject based on the ideXlab platform.
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intrarenal bradykinin elicits reno renal reflex sympatho excitation and renal nerve dependent fluid retention
Acta Physiologica, 2015Co-Authors: E F Barry, Edward J. JohnsAbstract:Aims The renal sensory nerves are importantly involved in the sympathetic regulation of cardiovascular and renal function. Two reno-renal reflexes are recognized, one in which activation of renal sensory nerves elicits a renal sympatho-inhibition, and one which causes a renal sympatho-excitation and about which little is known. This study investigated the role of bradykinin (BK) in engaging an excitatory reno-renal reflex. Methods Rats were anaesthetized (chloralose/urethane) and prepared for the measurement of renal function or renal sympathetic nerve activity (RSNA). BK was infused into the cortico-medullary border of the ipsilateral kidney and the impact on contralateral renal function and RSNA evaluated. Results Intrarenal infusion of BK at 3 × 10−9 and 6 × 10−9 g L−1 had no effect on mean arterial pressure, at 104 ± 5 mmHg or glomerular filtration rate in either the ipsilateral or contralateral kidneys, at 4.31 ± 0.45 mL min−1 kg−1. At the highest dose of BK, Fractional Sodium Excretion (FENa) was 1.47% in the ipsilateral kidney and was significantly lower, at 0.64% (P < 0.05) in the contralateral kidney but this difference did not occur following ipsilateral renal denervation. Ipsilateral intrarenal infusion of BK at 3 × 10−9, 6 × 10−9 and 1.2 × 10−8 g L−1 elicited dose-related increases (P < 0.05) in contralateral RSNA, reaching some 78% at the highest dose, but these responses were prevented by ipsilateral renal denervation. Conclusions Intrarenal infusion of BK produced an excitatory reno-renal reflex which was expressed as a renal nerve-dependent antinatriuresis in the contralateral kidney. The findings suggest that inflammatory mediators such as BK may be important in initiating a sympatho-excitation associated with renal and cardiovascular diseases.
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Neural regulation of the kidney function in rats with cisplatin induced renal failure
Frontiers Media S.A., 2015Co-Authors: Niamh E. Goulding, Edward J. JohnsAbstract:Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure.Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys.Results: Following the cisplatin challenge, creatinine clearance was 50% lower while Fractional Sodium Excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation.Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation
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effect of somatic nerve stimulation on the kidney in intact vagotomized and carotid sinus denervated rats
The Journal of Physiology, 1991Co-Authors: Gerard Davis, Edward J. JohnsAbstract:1. The influence of cardiopulmonary and arterial baroreceptors on the renal nerve-dependent functional responses of the kidney to electrical stimulation of somatic afferent nerves was studied in pentobarbitone-anaesthetized rats. 2. Electrical stimulation of the left brachial nerve plexus at 3 Hz, 0.2 ms and 15 V in the intact animals increased blood pressure by 22%, and while renal perfusion pressure was maintained at pre-stimulus levels, renal blood flow and glomerular filtration rate decreased by 14 and 22% respectively. At the same time urine flow rate and absolute and Fractional Sodium Excretion decreased by 36, 42 and 27% respectively. In animals subjected to acute renal nerve section these renal functional responses could not be elicited. 3. Following bilateral vagotomy the systemic and renal haemodynamic responses to brachial nerve stimulation were similar to the intact group. However, urine flow rate and absolute and Fractional Sodium Excretions decreased by 50, 59 and 47% respectively, responses which were significantly greater than in the intact group. 4. In a group of rats in which the carotid sinus nerves had been sectioned, stimulation of the brachial plexus caused reductions of renal blood flow and glomerular filtration rate of the same magnitude as in the intact group; however, urine flow rate and absolute and Fractional Sodium Excretion fell by 51, 60 and 48%, respectively, which were significantly larger than in the intact group. 5. These results demonstrate that the afferent nerve information arising from muscle joints and skin and carried via the brachial plexus caused reflex renal nerve-dependent reductions in renal haemodynamics and an antidiuresis and antinatriuresis. The cardiopulmonary and carotid sinus baroreceptors exert a tonic inhibitory action on these reflex renal responses insofar as they appeared to attenuate the antidiuretic and antinatriuretic responses to somatic afferent nerve stimulation.
Richard J Roman - One of the best experts on this subject based on the ideXlab platform.
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Normalization of pressure-natriuresis by nisoldipine in spontaneously hypertensive rats.
Hypertension, 1992Co-Authors: Francisco J. Fenoy, Michael L. Kauker, Ivan Milicic, Richard J RomanAbstract:This study examined whether the calcium antagonist nisoldipine can shift the relations between Sodium Excretion, papillary blood flow, renal interstitial pressure, and renal perfusion pressure toward lower pressures in spontaneously hypertensive rats. Mean arterial pressure decreased similarly by 9% and 12% in Wistar-Kyoto and spontaneously hypertensive rats after nisoldipine (0.5 microgram/kg bolus + 0.017 microgram/kg/min). Urine flow and Sodium Excretion increased by 35% and 24% in Wistar-Kyoto rats after nisoldipine. In contrast, urine flow and Sodium Excretion rose by 121% and 132% in spontaneously hypertensive rats, and Fractional Sodium Excretion rose from 1.9 +/- 0.3 to 4.2 +/- 0.4%. Control Sodium Excretion, papillary blood flow, and renal interstitial pressure were significantly lower in spontaneously hypertensive rats than in Wistar-Kyoto rats when compared at similar renal perfusion pressures. Sodium Excretion, papillary blood flow, and renal interstitial pressure all increased in spontaneously hypertensive rats after nisoldipine, whereas it had no effect on papillary blood flow or renal interstitial pressure in Wistar-Kyoto rats. The relations among Sodium Excretion, papillary blood flow, renal interstitial pressure, and renal perfusion pressure were shifted toward lower pressures in spontaneously hypertensive rats given nisoldipine and became similar to those seen in Wistar-Kyoto rats. These results indicate that nisoldipine normalizes the relations among Sodium Excretion, renal interstitial pressure, papillary blood flow, and renal perfusion pressure in spontaneously hypertensive rats perhaps by correcting the defect in renal medullary perfusion associated with resetting of pressure natriuresis in this model of hypertension.
Christopher J Kenyon - One of the best experts on this subject based on the ideXlab platform.
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Renal and Blood Pressure Response to a High-Salt Diet in Mice With Reduced Global Expression of the Glucocorticoid Receptor
Frontiers Media S.A., 2018Co-Authors: Jessica R. Ivy, Christopher J Kenyon, Louise C. Evans, Rebecca Moorhouse, Rachel V. Richardson, Emad A. S. Al-dujaili, Peter W. Flatman, Karen E. Chapman, Matthew A. BaileyAbstract:Salt-sensitive hypertension is common in glucocorticoid excess. Glucocorticoid resistance also presents with hypercortisolemia and hypertension but the relationship between salt intake and blood pressure (BP) is not well defined. GRβgeo/+ mice have global glucocorticoid receptor (GR) haploinsufficiency and increased BP. Here we examined the effect of high salt diet on BP, salt Excretion and renal blood flow in GRβgeo/+mice. Basal BP was ∼10 mmHg higher in male GRβgeo/+ mice than in GR+/+ littermates. This modest increase was amplified by ∼10 mmHg following a high-salt diet in GRβgeo/+ mice. High salt reduced urinary aldosterone Excretion but increased renal mineralocorticoid receptor expression in both genotypes. Corticosterone, and to a lesser extent deoxycorticosterone, Excretion was increased in GRβgeo/+ mice following a high-salt challenge, consistent with enhanced 24 h production. GR+/+ mice increased Fractional Sodium Excretion and reduced renal vascular resistance during the high salt challenge, retaining neutral Sodium balance. In contrast, Sodium Excretion and renal vascular resistance did not adapt to high salt in GRβgeo/+ mice, resulting in transient Sodium retention and sustained hypertension. With high-salt diet, Slc12a3 and Scnn1a mRNAs were higher in GRβgeo/+ than controls, and this was reflected in an exaggerated natriuretic response to thiazide and benzamil, inhibitors of NCC and ENaC, respectively. Reduction in GR expression causes salt-sensitivity and an adaptive failure of the renal vasculature and tubule, most likely reflecting sustained mineralocorticoid receptor activation. This provides a mechanistic basis to understand the hypertension associated with loss-of-function polymorphisms in GR in the context of habitually high salt intake
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mineralocorticoid and glucocorticoid receptors stimulate epithelial Sodium channel activity in a mouse model of cushing syndrome
Hypertension, 2009Co-Authors: Matthew A. Bailey, John J. Mullins, Christopher J KenyonAbstract:Experiments in Cushing patients and healthy control subjects receiving adrenocorticotropic hormone (ACTH) indicate that transient renal Sodium retention may contribute to the generation of hypertension. Here we have investigated the effect of chronic ACTH infusion on renal Sodium handling in adult male C57BL/6J mice using selective antagonists to dissect mineralocorticoid and glucocorticoid receptor–mediated pathways. Mice were infused via osmotic minipump with ACTH (2.5 μg/d) or saline for 2 weeks before being anesthetized for renal function experiments. ACTH caused an increase in blood pressure and a reduction in Fractional Sodium Excretion associated with enhanced activity of the epithelial Sodium channel. Given separately, spironolactone and RU38486 blunted the pressor response to ACTH and the increased epithelial Sodium channel activity; combined mineralocorticoid and glucocorticoid receptor blockade was required to resolve the response to ACTH excess. Dietary Sodium depletion also prevented ACTH-induced hypertension. The effect of increased Sodium reabsorption in the distal nephron is offset by downregulation of Na-K-Cl cotransport in the loop of Henle. Sodium Excretion is normalized chronically, but blood pressure remains high; acute blockade of V1 receptors and α1 adrenoceptors in combination restored blood pressure to control values. In summary, ACTH excess promotes renal Sodium reabsorption, contributing to the increased blood pressure; both glucocorticoid and mineralocorticoid receptor pathways are involved. These data are relevant to conditions associated with overactivity of the hypothalamic-pituitary-adrenal axis, such as obesity and chronic stress.
Xinli Li - One of the best experts on this subject based on the ideXlab platform.
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blood pressure and renal Sodium handling in relation to genetic variation in the drd1 promoter and grk4
Hypertension, 2008Co-Authors: Jan A Staessen, Tatiana Kuznetsova, Haifeng Zhang, Marc Maillard, Murielle Bochud, Sandra Hasenkamp, Judith Westerkamp, Tom Richart, Lutgarde Thijs, Xinli LiAbstract:Activation of type-1 dopamine receptors ( DRD1 ) reduces renal Sodium reabsorption. In a family-based random sample of 611 untreated whites (women, 45.0%; mean age, 38.6 years), we measured blood pressure (BP). We used the endogenous lithium clearance to assess Fractional Sodium Excretion (FE Na ) and proximal (RNa prox ) and distal (RNa dist ) tubular Sodium reabsorption. We investigated multivariate-adjusted associations with the DRD1 promoter ( A − 48G , G − 94A , and C − 800T ) and GRK4 (Ala142Val ). The frequent DRD1 haplotypes were AGC (48.2%), GGT (34.4%), and AAC (14.3%). While standardizing to mean Sodium Excretion (8.7 mmol/h) and adjusting for covariates and relatedness, RNa dist was lower in DRD1 − 94GG homozygotes than − 94A allele carriers (effect size, −0.94%; P =0.005) with opposite findings for FE Na (+0.084%; P =0.014). AGC carriers (−0.88%; P =0.012) and AAC carriers (+1.00%; P =0.004) had different RNa dist compared to corresponding noncarriers. Furthermore, FE Na was lower in AAC carriers than in noncarriers (−0.082%; P =0.019). The family-based analyses identified a significant between-family component in the variance of the renal phenotypes associated with the DRD1 polymorphisms. Transmission of the DRD1 AGC haplotype was also associated with lower systolic (−3.54 mm Hg; P =0.016) and diastolic (−2.80 mm Hg; P =0.0064) BPs without significant between-family variance component. Plasma renin activity and urinary aldosterone Excretion were not associated with DRD1 variation. The GRK4 Ala142Val polymorphism did not contribute to the phenotypes under study. In conclusion, renal Sodium handling and BP were associated with genetic variation in the DRD1 promoter. The between-family variance component excluded population stratification for BP, but not for the renal phenotypes.
Francisco J. Fenoy - One of the best experts on this subject based on the ideXlab platform.
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Normalization of pressure-natriuresis by nisoldipine in spontaneously hypertensive rats.
Hypertension, 1992Co-Authors: Francisco J. Fenoy, Michael L. Kauker, Ivan Milicic, Richard J RomanAbstract:This study examined whether the calcium antagonist nisoldipine can shift the relations between Sodium Excretion, papillary blood flow, renal interstitial pressure, and renal perfusion pressure toward lower pressures in spontaneously hypertensive rats. Mean arterial pressure decreased similarly by 9% and 12% in Wistar-Kyoto and spontaneously hypertensive rats after nisoldipine (0.5 microgram/kg bolus + 0.017 microgram/kg/min). Urine flow and Sodium Excretion increased by 35% and 24% in Wistar-Kyoto rats after nisoldipine. In contrast, urine flow and Sodium Excretion rose by 121% and 132% in spontaneously hypertensive rats, and Fractional Sodium Excretion rose from 1.9 +/- 0.3 to 4.2 +/- 0.4%. Control Sodium Excretion, papillary blood flow, and renal interstitial pressure were significantly lower in spontaneously hypertensive rats than in Wistar-Kyoto rats when compared at similar renal perfusion pressures. Sodium Excretion, papillary blood flow, and renal interstitial pressure all increased in spontaneously hypertensive rats after nisoldipine, whereas it had no effect on papillary blood flow or renal interstitial pressure in Wistar-Kyoto rats. The relations among Sodium Excretion, papillary blood flow, renal interstitial pressure, and renal perfusion pressure were shifted toward lower pressures in spontaneously hypertensive rats given nisoldipine and became similar to those seen in Wistar-Kyoto rats. These results indicate that nisoldipine normalizes the relations among Sodium Excretion, renal interstitial pressure, papillary blood flow, and renal perfusion pressure in spontaneously hypertensive rats perhaps by correcting the defect in renal medullary perfusion associated with resetting of pressure natriuresis in this model of hypertension.
