The Experts below are selected from a list of 75 Experts worldwide ranked by ideXlab platform
C J Garland - One of the best experts on this subject based on the ideXlab platform.
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vascular hyperpolarization to β adrenoceptor agonists evokes spreading dilatation in rat Isolated mesenteric arteries
British Journal of Pharmacology, 2011Co-Authors: C J Garland, Polina Yarova, Francesc Jimenezaltayo, K A DoraAbstract:BACKGROUND AND PURPOSE β-Adrenoceptor stimulation causes pronounced vasodilatation associated with smooth muscle hyperpolarization. Although the hyperpolarization is known to reflect KATP channel activation, it is not known to what extent it contributes to vasodilatation. EXPERIMENTAL APPROACH Smooth muscle membrane potential and tension were measured simultaneously in small mesenteric arteries in a wire myograph. The spread of vasodilatation over distance was assessed in pressurized arteries following localized intraluminal perfusion of either isoprenaline, adrenaline or noradrenaline. KEY RESULTS Isoprenaline stimulated rapid smooth muscle relaxation associated at higher concentrations with robust hyperpolarization. Noradrenaline or adrenaline evoked a similar hyperpolarization to isoprenaline if the α1-adrenoceptor antagonist prazosin was present. With each agonist, glibenclamide blocked hyperpolarization without reducing relaxation. Focal, intraluminal application of isoprenaline, noradrenaline or adrenaline during block of α1-adrenoceptors evoked a dilatation that spread along the entire length of the Isolated Artery. This response was endothelium-dependent and inhibited by glibenclamide. CONCLUSIONS AND IMPLICATIONS Hyperpolarization is not essential for β-adrenoceptor-mediated vasodilatation. However, following focal β-adrenoceptor stimulation, this hyperpolarization underlies the ability of vasodilatation to spread along the Artery wall. The consequent spread of vasodilatation is dependent upon the endothelium and likely to be of physiological relevance in the coordination of tissue blood flow. LINKED ARTICLES This article is part of a themed issue on Vascular Endothelium in Health and Disease. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-3
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spreading dilatation in rat mesenteric arteries associated with calcium independent endothelial cell hyperpolarization
The Journal of Physiology, 2004Co-Authors: Hiromichi Takano, K A Dora, Michaela M Spitaler, C J GarlandAbstract:Both ACh and levcromakalim evoke smooth muscle cell hyperpolarization and associated relaxation in rat mesenteric resistance arteries. We investigated if they could evoke conducted vasodilatation along Isolated arteries, whether this reflected spreading hyperpolarization and the possible mechanism involved. Focal micropipette application of either ACh, to stimulate endothelial cell muscarinic receptors, or levcromakalim, to activate smooth muscle KATP channels, each evoked a local dilatation (88 ± 14%, n= 6 and 92 ± 6% reversal of phenylephrine-induced tone, n= 11, respectively) that rapidly spread upstream (at 1.5 mm 46 ± 19%, n= 6 and 57 ± 13%, n= 9) to dilate the entire Isolated Artery. The local dilatation to ACh was associated with a rise in endothelial cell [Ca2+]i (F/Ft = 0= 1.22 ± 0.33, n= 14) which did not spread beyond 0.5 mm (F/Ft = 0= 1.01 ± 0.01, n= 14), while the local dilatation to levcromakalim was not associated with any change in endothelial cell [Ca2+]i. In contrast, ACh and levcromakalim both stimulated local (12.7 ± 1.2 mV, n= 10 and 13.5 ± 4.7 mV, n= 10) and spreading (at 2 mm: 3.0 ± 1.1 mV, n= 5 and 4.1 ± 0.7 mV, n= 5) smooth muscle hyperpolarization. The spread of hyperpolarization could be prevented by cutting the Artery, so was not due to a diffusible agent. Both the spreading dilatation and hyperpolarization were endothelium dependent. The injection of propidium iodide into either endothelial or smooth muscle cells revealed extensive dye coupling between the endothelial cells, but limited coupling between the smooth muscle cells. Some evidence for heterocellular spread of dye was also evident. Together, these data show that vasodilatation can spread over significant distances in mesenteric resistance arteries, and suggest this reflects an effective coupling between the endothelial cells to facilitate [Ca2+]i-independent spread of hyperpolarization.
K A Dora - One of the best experts on this subject based on the ideXlab platform.
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vascular hyperpolarization to β adrenoceptor agonists evokes spreading dilatation in rat Isolated mesenteric arteries
British Journal of Pharmacology, 2011Co-Authors: C J Garland, Polina Yarova, Francesc Jimenezaltayo, K A DoraAbstract:BACKGROUND AND PURPOSE β-Adrenoceptor stimulation causes pronounced vasodilatation associated with smooth muscle hyperpolarization. Although the hyperpolarization is known to reflect KATP channel activation, it is not known to what extent it contributes to vasodilatation. EXPERIMENTAL APPROACH Smooth muscle membrane potential and tension were measured simultaneously in small mesenteric arteries in a wire myograph. The spread of vasodilatation over distance was assessed in pressurized arteries following localized intraluminal perfusion of either isoprenaline, adrenaline or noradrenaline. KEY RESULTS Isoprenaline stimulated rapid smooth muscle relaxation associated at higher concentrations with robust hyperpolarization. Noradrenaline or adrenaline evoked a similar hyperpolarization to isoprenaline if the α1-adrenoceptor antagonist prazosin was present. With each agonist, glibenclamide blocked hyperpolarization without reducing relaxation. Focal, intraluminal application of isoprenaline, noradrenaline or adrenaline during block of α1-adrenoceptors evoked a dilatation that spread along the entire length of the Isolated Artery. This response was endothelium-dependent and inhibited by glibenclamide. CONCLUSIONS AND IMPLICATIONS Hyperpolarization is not essential for β-adrenoceptor-mediated vasodilatation. However, following focal β-adrenoceptor stimulation, this hyperpolarization underlies the ability of vasodilatation to spread along the Artery wall. The consequent spread of vasodilatation is dependent upon the endothelium and likely to be of physiological relevance in the coordination of tissue blood flow. LINKED ARTICLES This article is part of a themed issue on Vascular Endothelium in Health and Disease. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-3
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spreading dilatation in rat mesenteric arteries associated with calcium independent endothelial cell hyperpolarization
The Journal of Physiology, 2004Co-Authors: Hiromichi Takano, K A Dora, Michaela M Spitaler, C J GarlandAbstract:Both ACh and levcromakalim evoke smooth muscle cell hyperpolarization and associated relaxation in rat mesenteric resistance arteries. We investigated if they could evoke conducted vasodilatation along Isolated arteries, whether this reflected spreading hyperpolarization and the possible mechanism involved. Focal micropipette application of either ACh, to stimulate endothelial cell muscarinic receptors, or levcromakalim, to activate smooth muscle KATP channels, each evoked a local dilatation (88 ± 14%, n= 6 and 92 ± 6% reversal of phenylephrine-induced tone, n= 11, respectively) that rapidly spread upstream (at 1.5 mm 46 ± 19%, n= 6 and 57 ± 13%, n= 9) to dilate the entire Isolated Artery. The local dilatation to ACh was associated with a rise in endothelial cell [Ca2+]i (F/Ft = 0= 1.22 ± 0.33, n= 14) which did not spread beyond 0.5 mm (F/Ft = 0= 1.01 ± 0.01, n= 14), while the local dilatation to levcromakalim was not associated with any change in endothelial cell [Ca2+]i. In contrast, ACh and levcromakalim both stimulated local (12.7 ± 1.2 mV, n= 10 and 13.5 ± 4.7 mV, n= 10) and spreading (at 2 mm: 3.0 ± 1.1 mV, n= 5 and 4.1 ± 0.7 mV, n= 5) smooth muscle hyperpolarization. The spread of hyperpolarization could be prevented by cutting the Artery, so was not due to a diffusible agent. Both the spreading dilatation and hyperpolarization were endothelium dependent. The injection of propidium iodide into either endothelial or smooth muscle cells revealed extensive dye coupling between the endothelial cells, but limited coupling between the smooth muscle cells. Some evidence for heterocellular spread of dye was also evident. Together, these data show that vasodilatation can spread over significant distances in mesenteric resistance arteries, and suggest this reflects an effective coupling between the endothelial cells to facilitate [Ca2+]i-independent spread of hyperpolarization.
Kazūne Sigita - One of the best experts on this subject based on the ideXlab platform.
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Artēriju funkcionālo parametru loma multiorgānu disfunkcijas sindroma progresēšanas riska prognozēšanā sepses slimniekiem. Promocijas darba kopsavilkums
'Riga Stradins University', 2020Co-Authors: Kazūne SigitaAbstract:The Doctoral thesis was carried out at Rīga Stradiņš University. Defence: at the public session of the Doctoral Council of Clinical Medicine on 30 June 2020 at 15.00 in Hippocrates Lecture Theatre, 16 Dzirciema Street, Rīga Stradiņš University.Sepsis is defined as multiple organ damage caused by dysfunctional systemic host response to infection. It is a frequent cause of admission to intensive care unit and carries high mortality. Vascular dysfunction due to reduced nitric oxide bioavailability plays an important role in the pathogenesis of sepsis and multiple organ failure. Conduit arteries, especially the aorta, play a major role in ensuring efficient cardiac function and optimal flow in the periphery due to their viscoelastic properties. Resistance arteries and arterioles adjust peripheral blood flow according to the metabolic needs of the tissues. Laboratory studies on Isolated Artery models and animal research show that acute systemic inflammation can cause impaired vasoreactivity in peripheral vascular beds and aortic stiffening of conduit arteries which affects hemodynamic efficiency. This thesis aims to characterize parameters describing functional properties of arteries in intensive care patients with severe sepsis and septic shock and clarify their association with the development of multiple organ dysfunction syndrome and mortality. This thesis consists of three parts. In part 1, systematic review and meta-analysis of published literature were performed to evaluate the measurement of endothelial function using vasoreactivity tests as a risk stratification tool in intensive care patients with sepsis. From the studies included in this review, there is evidence of moderate strength that vascular reactivity is impaired in septic patients, but not enough evidence has been provided to suggest that it is a consequence of endothelial dysfunction or is convincingly related to clinical outcomes. In part 2, the author undertook a prospective observational cohort study examining aortic stiffness in patients with sepsis using carotid-femoral pulse wave velocity measurement. Forty-five adult intensive care patients were recruited to the study within 24 hours of admission to intensive care. Carotid-femoral pulse wave velocity was measured once initial resuscitation was completed. Patients were followed up to hospital discharge or death. This study found that patients with severe sepsis and septic shock have higher aortic stiffness than the general population. No convincing association was found between admission pulse wave velocity and progression of multiple organ failure or mortality, although the group with pulse wave velocity > 24.7 m/s had shorter survival time. Part 3 extends the previous study and examines stiffness of both elastic and muscular arteries at two time points, at admission and after 48 hours of treatment. It also examines confounders associated with changes in carotid-femoral and carotid-radial pulse wave velocity. It found increased aortic and even higher upper limb Artery stiffness among the septic population. Higher carotid-femoral pulse wave velocity was associated with higher mean arterial blood pressure and lower C reactive protein concentration. Pulse wave velocity in elastic and muscular arteries decreased after a 48-hour treatment period in survivors. In non-survivors, carotid-radial pulse wave velocity stayed consistently high. Overall, this study has shown that altered static and dynamic parameters of Artery function are highly prevalent in patients with sepsis and associated with unfavourable outcome. Longitudinal assessment of these parameters has the potential to be used for risk stratification in patients with early sepsis
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Artēriju funkcionālo parametru loma multiorgānu disfunkcijas sindroma progresēšanas riska prognozēšanā sepses slimniekiem. Promocijas darbs
'Riga Stradins University', 2020Co-Authors: Kazūne SigitaAbstract:The Doctoral thesis was carried out at Rīga Stradiņš University. Defence: at the public session of the Doctoral Council of Clinical Medicine on 30 June 2020 at 15.00 in Hippocrates Lecture Theatre, 16 Dzirciema Street, Rīga Stradiņš University.Sepsis is defined as multiple organ damage caused by dysfunctional systemic host response to infection. It is a frequent cause of admission to intensive care unit and carries high mortality. Vascular dysfunction due to reduced nitric oxide bioavailability plays an important role in the pathogenesis of sepsis and multiple organ failure. Conduit arteries, especially the aorta, play a major role in ensuring efficient cardiac function and optimal flow in the periphery due to their viscoelastic properties. Resistance arteries and arterioles adjust peripheral blood flow according to the metabolic needs of the tissues. Laboratory studies on Isolated Artery models and animal research show that acute systemic inflammation can cause impaired vasoreactivity in peripheral vascular beds and aortic stiffening of conduit arteries which affects hemodynamic efficiency. This thesis aims to characterize parameters describing functional properties of arteries in intensive care patients with severe sepsis and septic shock and clarify their association with the development of multiple organ dysfunction syndrome and mortality. This thesis consists of three parts. In part 1, systematic review and meta-analysis of published literature were performed to evaluate the measurement of endothelial function using vasoreactivity tests as a risk stratification tool in intensive care patients with sepsis. From the studies included in this review, there is evidence of moderate strength that vascular reactivity is impaired in septic patients, but not enough evidence has been provided to suggest that it is a consequence of endothelial dysfunction or is convincingly related to clinical outcomes. In part 2, the author undertook a prospective observational cohort study examining aortic stiffness in patients with sepsis using carotid-femoral pulse wave velocity measurement. Forty-five adult intensive care patients were recruited to the study within 24 hours of admission to intensive care. Carotid-femoral pulse wave velocity was measured once initial resuscitation was completed. Patients were followed up to hospital discharge or death. This study found that patients with severe sepsis and septic shock have higher aortic stiffness than the general population. No convincing association was found between admission pulse wave velocity and progression of multiple organ failure or mortality, although the group with pulse wave velocity > 24.7 m/s had shorter survival time. Part 3 extends the previous study and examines stiffness of both elastic and muscular arteries at two time points, at admission and after 48 hours of treatment. It also examines confounders associated with changes in carotid-femoral and carotid-radial pulse wave velocity. It found increased aortic and even higher upper limb Artery stiffness among the septic population. Higher carotid-femoral pulse wave velocity was associated with higher mean arterial blood pressure and lower C reactive protein concentration. Pulse wave velocity in elastic and muscular arteries decreased after a 48-hour treatment period in survivors. In non-survivors, carotid-radial pulse wave velocity stayed consistently high. Overall, this study has shown that altered static and dynamic parameters of Artery function are highly prevalent in patients with sepsis and associated with unfavourable outcome. Longitudinal assessment of these parameters has the potential to be used for risk stratification in patients with early sepsis
Hiromichi Takano - One of the best experts on this subject based on the ideXlab platform.
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spreading dilatation in rat mesenteric arteries associated with calcium independent endothelial cell hyperpolarization
The Journal of Physiology, 2004Co-Authors: Hiromichi Takano, K A Dora, Michaela M Spitaler, C J GarlandAbstract:Both ACh and levcromakalim evoke smooth muscle cell hyperpolarization and associated relaxation in rat mesenteric resistance arteries. We investigated if they could evoke conducted vasodilatation along Isolated arteries, whether this reflected spreading hyperpolarization and the possible mechanism involved. Focal micropipette application of either ACh, to stimulate endothelial cell muscarinic receptors, or levcromakalim, to activate smooth muscle KATP channels, each evoked a local dilatation (88 ± 14%, n= 6 and 92 ± 6% reversal of phenylephrine-induced tone, n= 11, respectively) that rapidly spread upstream (at 1.5 mm 46 ± 19%, n= 6 and 57 ± 13%, n= 9) to dilate the entire Isolated Artery. The local dilatation to ACh was associated with a rise in endothelial cell [Ca2+]i (F/Ft = 0= 1.22 ± 0.33, n= 14) which did not spread beyond 0.5 mm (F/Ft = 0= 1.01 ± 0.01, n= 14), while the local dilatation to levcromakalim was not associated with any change in endothelial cell [Ca2+]i. In contrast, ACh and levcromakalim both stimulated local (12.7 ± 1.2 mV, n= 10 and 13.5 ± 4.7 mV, n= 10) and spreading (at 2 mm: 3.0 ± 1.1 mV, n= 5 and 4.1 ± 0.7 mV, n= 5) smooth muscle hyperpolarization. The spread of hyperpolarization could be prevented by cutting the Artery, so was not due to a diffusible agent. Both the spreading dilatation and hyperpolarization were endothelium dependent. The injection of propidium iodide into either endothelial or smooth muscle cells revealed extensive dye coupling between the endothelial cells, but limited coupling between the smooth muscle cells. Some evidence for heterocellular spread of dye was also evident. Together, these data show that vasodilatation can spread over significant distances in mesenteric resistance arteries, and suggest this reflects an effective coupling between the endothelial cells to facilitate [Ca2+]i-independent spread of hyperpolarization.
Jan Weis - One of the best experts on this subject based on the ideXlab platform.
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Effects on Isolated arteries from rat, rabbit and man of NNC 70-0270, a synthtetic atrial natrinretic factor analogue with a prolonged action
European journal of pharmacology, 1991Co-Authors: Jan WeisAbstract:Abstract A new analogue of ANF (atrial natriuretic factor), NNC 70-0270, was tested in various Isolated Artery preparations. In the rabbit aorta and renal Artery NNC 70-0270 was compared with atriopeptin III and the relative inhibitory potency aganist noradrenaline-induced contractions (atriopeptin III = 1) was found to be 5 and 9, respectively. Furthermore the duration of the effect (after washout) was prolonged. In the rat aorta the relative potency was 0.5 and a prolonged effect was also found in this preparation. In the human pulmonary Artery α-hANF was used as a reference, and contractions were induced with noradrenaline (seven experiments) or potassium chloride (three experiments). The relative ( α -hANF = 1) inhibitory potencies were 0.8 and 1.3, respectively. A pronounced prolongation of the effect was also found in this preparation.
