The Experts below are selected from a list of 1182 Experts worldwide ranked by ideXlab platform
William B. Campbell - One of the best experts on this subject based on the ideXlab platform.
-
obligatory metabolism of angiotensin ii to angiotensin iii for zona glomerulosa cell mediated relaxations of bovine Adrenal cortical arteries
Endocrinology, 2018Co-Authors: Phillip G Kopf, Bernard P Roques, Sangkyu Park, Anja Herrnreiter, Christian Krause, William B. CampbellAbstract:: Hyperaldosteronism is associated with hypertension, cardiac hypertrophy, and congestive heart failure. Steroidogenic factors facilitate aldosterone secretion by increasing Adrenal Blood Flow. Angiotensin (Ang) II decreases Adrenal vascular tone through release of zona glomerulosa (ZG) cell-derived vasodilatory eicosanoids. However, ZG cell-mediated relaxation of bovine Adrenal cortical arteries to Ang II is not altered by angiotensin type 1 or 2 receptor antagonists. Because traditional Ang II receptors do not mediate these vasorelaxations to Ang II, we investigated the role of Ang II metabolites. Ang III was identified by liquid chromatography-mass spectrometry as the primary ZG cell metabolite of Ang II. Ang III stimulated ZG cell-mediated relaxation of Adrenal arteries with greater potency than did Ang II. Furthermore, ZG cell-mediated relaxations of Adrenal arteries by Ang II were attenuated by aminopeptidase inhibition, and Ang III-stimulated relaxations persisted. Ang IV had little effect compared with Ang II. Moreover, ZG cell-mediated relaxations of Adrenal arteries by Ang II were attenuated by an Ang III antagonist but not by an Ang (1-7) antagonist. In contrast, Ang II and Ang III were equipotent in stimulating aldosterone secretion from ZG cells and were unaffected by aminopeptidase inhibition. Additionally, aspartyl and leucyl aminopeptidases, which convert Ang II to Ang III, are the primary peptidase expressed in ZG cells. This was confirmed by enzyme activity. These data indicate that intra-Adrenal metabolism of Ang II to Ang III is required for ZG cell-mediated relaxations of Adrenal arteries but not aldosterone secretion. These studies have defined an important role of Ang III in the Adrenal gland.
-
Angiotensin II Regulates Adrenal Vascular Tone Through
2016Co-Authors: Zona Glomerulosa, Phillip G Kopf, Kathryn M Gauthier, David X Zhang, John R Falck, William B. CampbellAbstract:Abstract—Elevated concentrations of aldosterone are associated with several cardiovascular diseases. Angiotensin II (Ang II) increases aldosterone secretion and Adrenal Blood Flow. This concurrent increase in steroidogenesis and Adrenal Blood Flow is not understood. We investigated the role of zona glomerulosa (ZG) cells in the regulation of vascular tone of bovine Adrenal cortical arteries by Ang II. ZG cells enhanced endothelium-dependent relaxations to Ang II. The ZG cell–dependent relaxations to Ang II were unchanged by removing the endothelium-dependent response to Ang II. These ZG cell–mediated relaxations were ablated by cytochrome P450 inhibition, epoxyeicosatrienoic acid (EET) antagonism, and potassium channel blockade. Analysis of ZG cell EET production by liquid chromatography/mass spectrometry demonstrated an increase in EETs and dihydroxyeicosatrienoic acids with Ang II stimulation. These EETs and dihydroxyeicosatrienoic acids produced similar concentration-dependent relaxations of Adrenal arteries, which were attenuated by EET antagonism. Whole-cell potassium currents of Adrenal artery smooth muscle cells were increased by Ang II stimulation in the presence of ZG cells but decreased in the absence of ZG cells. This increase in potassium current was abolished by iberiotoxin. Similarly, 14,15-EET induced concentration-dependent increases in potassium current, which was abolished by iberiotoxin. ZG cell aldosterone release was not directly altered by EETs. These data suggest that Ang II stimulates ZG cells to release EETs and dihydroxyeicosatrienoic acids, resulting in potassium channel activation and relaxation of Adrenal arteries. This provides a mechanism by which Ang II concurrently increase
-
Running title: Histamine and Adrenal cortical arterial tone Send Correspondence and Reprint Requests to:
2013Co-Authors: David X Zhang, Kathryn M Gauthier, William B. CampbellAbstract:Adrenal steroidogenesis is closely correlated with increases in Adrenal Blood Flow. Many reports have studied the regulation of Adrenal Blood Flow in vivo and in perfused glands, but until recently few studies have been conducted on isolated Adrenal Blood arteries. The present study examined vasomotor responses of small isolated bovine small Adrenal cortical arteries to histamine, an endogenous vasoactive compound, and its mechanism of action. In U46619precontracted arteries, histamine (10-9-5x10-6 M) elicited concentration-dependent relaxations. The relaxations were blocked by the H1-receptor antagonists diphenhydramine (10 µM) or mepyramine (1 µM) (maximal relaxations of 18±6 % and 22 ±6 % respectively vs. 55±5 % of control), but only partially inhibited by the H2-receptor antagonist cimetidine (10 µM) and the H3-receptor antagonist thioperamide (1 µM). Histamine-induced relaxations were also blocked by the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA, 30 µM; maximal relaxation of 13±7%) and eliminated by endothelial removal and L-NA combined with the cyclooxgenase inhibitor indomethacin (10 µM). In the presence of Adrenal zona glomerulosa (ZG) cells, histamine did not induce further relaxations compared to histamine alone. Histamine (10-7-10-5 M) concentration-dependently increased aldosterone production by Adrenal ZG cells. Compound 48/80 (10 µg/ml), a mast cell degranulator, induced significant relaxation (93±0.6%), whic
-
angiotensin ii regulates Adrenal vascular tone through zona glomerulosa cell derived eets and dhets
Hypertension, 2011Co-Authors: Phillip G Kopf, Kathryn M Gauthier, David X Zhang, John R Falck, William B. CampbellAbstract:Elevated concentrations of aldosterone are associated with several cardiovascular diseases. Angiotensin II (Ang II) increases aldosterone secretion and Adrenal Blood Flow. This concurrent increase in steroidogenesis and Adrenal Blood Flow is not understood. We investigated the role of zona glomerulosa (ZG) cells in the regulation of vascular tone of bovine Adrenal cortical arteries by Ang II. ZG cells enhanced endothelium-dependent relaxations to Ang II. The ZG cell–dependent relaxations to Ang II were unchanged by removing the endothelium-dependent response to Ang II. These ZG cell–mediated relaxations were ablated by cytochrome P450 inhibition, epoxyeicosatrienoic acid (EET) antagonism, and potassium channel blockade. Analysis of ZG cell EET production by liquid chromatography/mass spectrometry demonstrated an increase in EETs and dihydroxyeicosatrienoic acids with Ang II stimulation. These EETs and dihydroxyeicosatrienoic acids produced similar concentration-dependent relaxations of Adrenal arteries, which were attenuated by EET antagonism. Whole-cell potassium currents of Adrenal artery smooth muscle cells were increased by Ang II stimulation in the presence of ZG cells but decreased in the absence of ZG cells. This increase in potassium current was abolished by iberiotoxin. Similarly, 14,15-EET induced concentration-dependent increases in potassium current, which was abolished by iberiotoxin. ZG cell aldosterone release was not directly altered by EETs. These data suggest that Ang II stimulates ZG cells to release EETs and dihydroxyeicosatrienoic acids, resulting in potassium channel activation and relaxation of Adrenal arteries. This provides a mechanism by which Ang II concurrently increases Adrenal Blood Flow and steroidogenesis.
-
adrenic acid metabolites as endogenous endothelium derived and zona glomerulosa derived hyperpolarizing factors
Hypertension, 2010Co-Authors: Phillip G Kopf, Xiu Yu Yi, Kasem Nithipatikom, Kathryn M Gauthier, David X Zhang, John R Falck, William B. CampbellAbstract:Adrenic acid (docosatetraenoic acid), an abundant fatty acid in the Adrenal gland, is identical to arachidonic acid except for 2 additional carbons on the carboxyl end. Adrenic acid is metabolized by cyclooxygenases, cytochrome P450s, and lipoxygenases; however, little is known regarding the role of adrenic acid and its metabolites in vascular tone. Because of its abundance in the Adrenal gland, we investigated the role of adrenic acid in vascular tone of bovine Adrenal cortical arteries and its metabolism by bovine Adrenal zona glomerulosa cells. In Adrenal cortical arteries, adrenic acid caused concentration-dependent relaxations, which were inhibited by the epoxyeicosatrienoic acid antagonist 14,15-epoxyeicosa-5(Z)-enoic acid and the cytochrome P450 inhibitor SKF-525A. The large-conductance calcium-activated potassium channel blocker iberiotoxin or removal of the endothelium abolished these relaxations. Reverse-phase high-pressure liquid chromatography and liquid chromatography/mass spectrometry isolated and identified numerous adrenic acid metabolites from zona glomerulosa cells, including dihomo-epoxyeicosatrienoic acids and dihomo-prostaglandins. In denuded Adrenal cortical arteries, adrenic acid caused concentration-dependent relaxations in the presence of zona glomerulosa cells but not in their absence. These relaxations were inhibited by SKF-525A, 14,15-epoxyeicosa-5(Z)-enoic acid, and iberiotoxin. Dihomo-16,17-epoxyeicosatrienoic acid caused concentration-dependent relaxations of Adrenal cortical arteries, which were inhibited by 14,15-epoxyeicosa-5(Z)-enoic acid and high potassium. Our results suggest that adrenic acid relaxations of bovine Adrenal cortical arteries are mediated by endothelial and zona glomerulosa cell cytochrome P450 metabolites. Thus, adrenic acid metabolites could function as endogenous endothelium-derived and zona glomerulosa-derived hyperpolarizing factors in the Adrenal cortex and contribute to the regulation of Adrenal Blood Flow.
Phillip G Kopf - One of the best experts on this subject based on the ideXlab platform.
-
obligatory metabolism of angiotensin ii to angiotensin iii for zona glomerulosa cell mediated relaxations of bovine Adrenal cortical arteries
Endocrinology, 2018Co-Authors: Phillip G Kopf, Bernard P Roques, Sangkyu Park, Anja Herrnreiter, Christian Krause, William B. CampbellAbstract:: Hyperaldosteronism is associated with hypertension, cardiac hypertrophy, and congestive heart failure. Steroidogenic factors facilitate aldosterone secretion by increasing Adrenal Blood Flow. Angiotensin (Ang) II decreases Adrenal vascular tone through release of zona glomerulosa (ZG) cell-derived vasodilatory eicosanoids. However, ZG cell-mediated relaxation of bovine Adrenal cortical arteries to Ang II is not altered by angiotensin type 1 or 2 receptor antagonists. Because traditional Ang II receptors do not mediate these vasorelaxations to Ang II, we investigated the role of Ang II metabolites. Ang III was identified by liquid chromatography-mass spectrometry as the primary ZG cell metabolite of Ang II. Ang III stimulated ZG cell-mediated relaxation of Adrenal arteries with greater potency than did Ang II. Furthermore, ZG cell-mediated relaxations of Adrenal arteries by Ang II were attenuated by aminopeptidase inhibition, and Ang III-stimulated relaxations persisted. Ang IV had little effect compared with Ang II. Moreover, ZG cell-mediated relaxations of Adrenal arteries by Ang II were attenuated by an Ang III antagonist but not by an Ang (1-7) antagonist. In contrast, Ang II and Ang III were equipotent in stimulating aldosterone secretion from ZG cells and were unaffected by aminopeptidase inhibition. Additionally, aspartyl and leucyl aminopeptidases, which convert Ang II to Ang III, are the primary peptidase expressed in ZG cells. This was confirmed by enzyme activity. These data indicate that intra-Adrenal metabolism of Ang II to Ang III is required for ZG cell-mediated relaxations of Adrenal arteries but not aldosterone secretion. These studies have defined an important role of Ang III in the Adrenal gland.
-
Angiotensin II Regulates Adrenal Vascular Tone Through
2016Co-Authors: Zona Glomerulosa, Phillip G Kopf, Kathryn M Gauthier, David X Zhang, John R Falck, William B. CampbellAbstract:Abstract—Elevated concentrations of aldosterone are associated with several cardiovascular diseases. Angiotensin II (Ang II) increases aldosterone secretion and Adrenal Blood Flow. This concurrent increase in steroidogenesis and Adrenal Blood Flow is not understood. We investigated the role of zona glomerulosa (ZG) cells in the regulation of vascular tone of bovine Adrenal cortical arteries by Ang II. ZG cells enhanced endothelium-dependent relaxations to Ang II. The ZG cell–dependent relaxations to Ang II were unchanged by removing the endothelium-dependent response to Ang II. These ZG cell–mediated relaxations were ablated by cytochrome P450 inhibition, epoxyeicosatrienoic acid (EET) antagonism, and potassium channel blockade. Analysis of ZG cell EET production by liquid chromatography/mass spectrometry demonstrated an increase in EETs and dihydroxyeicosatrienoic acids with Ang II stimulation. These EETs and dihydroxyeicosatrienoic acids produced similar concentration-dependent relaxations of Adrenal arteries, which were attenuated by EET antagonism. Whole-cell potassium currents of Adrenal artery smooth muscle cells were increased by Ang II stimulation in the presence of ZG cells but decreased in the absence of ZG cells. This increase in potassium current was abolished by iberiotoxin. Similarly, 14,15-EET induced concentration-dependent increases in potassium current, which was abolished by iberiotoxin. ZG cell aldosterone release was not directly altered by EETs. These data suggest that Ang II stimulates ZG cells to release EETs and dihydroxyeicosatrienoic acids, resulting in potassium channel activation and relaxation of Adrenal arteries. This provides a mechanism by which Ang II concurrently increase
-
angiotensin ii regulates Adrenal vascular tone through zona glomerulosa cell derived eets and dhets
Hypertension, 2011Co-Authors: Phillip G Kopf, Kathryn M Gauthier, David X Zhang, John R Falck, William B. CampbellAbstract:Elevated concentrations of aldosterone are associated with several cardiovascular diseases. Angiotensin II (Ang II) increases aldosterone secretion and Adrenal Blood Flow. This concurrent increase in steroidogenesis and Adrenal Blood Flow is not understood. We investigated the role of zona glomerulosa (ZG) cells in the regulation of vascular tone of bovine Adrenal cortical arteries by Ang II. ZG cells enhanced endothelium-dependent relaxations to Ang II. The ZG cell–dependent relaxations to Ang II were unchanged by removing the endothelium-dependent response to Ang II. These ZG cell–mediated relaxations were ablated by cytochrome P450 inhibition, epoxyeicosatrienoic acid (EET) antagonism, and potassium channel blockade. Analysis of ZG cell EET production by liquid chromatography/mass spectrometry demonstrated an increase in EETs and dihydroxyeicosatrienoic acids with Ang II stimulation. These EETs and dihydroxyeicosatrienoic acids produced similar concentration-dependent relaxations of Adrenal arteries, which were attenuated by EET antagonism. Whole-cell potassium currents of Adrenal artery smooth muscle cells were increased by Ang II stimulation in the presence of ZG cells but decreased in the absence of ZG cells. This increase in potassium current was abolished by iberiotoxin. Similarly, 14,15-EET induced concentration-dependent increases in potassium current, which was abolished by iberiotoxin. ZG cell aldosterone release was not directly altered by EETs. These data suggest that Ang II stimulates ZG cells to release EETs and dihydroxyeicosatrienoic acids, resulting in potassium channel activation and relaxation of Adrenal arteries. This provides a mechanism by which Ang II concurrently increases Adrenal Blood Flow and steroidogenesis.
-
adrenic acid metabolites as endogenous endothelium derived and zona glomerulosa derived hyperpolarizing factors
Hypertension, 2010Co-Authors: Phillip G Kopf, Xiu Yu Yi, Kasem Nithipatikom, Kathryn M Gauthier, David X Zhang, John R Falck, William B. CampbellAbstract:Adrenic acid (docosatetraenoic acid), an abundant fatty acid in the Adrenal gland, is identical to arachidonic acid except for 2 additional carbons on the carboxyl end. Adrenic acid is metabolized by cyclooxygenases, cytochrome P450s, and lipoxygenases; however, little is known regarding the role of adrenic acid and its metabolites in vascular tone. Because of its abundance in the Adrenal gland, we investigated the role of adrenic acid in vascular tone of bovine Adrenal cortical arteries and its metabolism by bovine Adrenal zona glomerulosa cells. In Adrenal cortical arteries, adrenic acid caused concentration-dependent relaxations, which were inhibited by the epoxyeicosatrienoic acid antagonist 14,15-epoxyeicosa-5(Z)-enoic acid and the cytochrome P450 inhibitor SKF-525A. The large-conductance calcium-activated potassium channel blocker iberiotoxin or removal of the endothelium abolished these relaxations. Reverse-phase high-pressure liquid chromatography and liquid chromatography/mass spectrometry isolated and identified numerous adrenic acid metabolites from zona glomerulosa cells, including dihomo-epoxyeicosatrienoic acids and dihomo-prostaglandins. In denuded Adrenal cortical arteries, adrenic acid caused concentration-dependent relaxations in the presence of zona glomerulosa cells but not in their absence. These relaxations were inhibited by SKF-525A, 14,15-epoxyeicosa-5(Z)-enoic acid, and iberiotoxin. Dihomo-16,17-epoxyeicosatrienoic acid caused concentration-dependent relaxations of Adrenal cortical arteries, which were inhibited by 14,15-epoxyeicosa-5(Z)-enoic acid and high potassium. Our results suggest that adrenic acid relaxations of bovine Adrenal cortical arteries are mediated by endothelial and zona glomerulosa cell cytochrome P450 metabolites. Thus, adrenic acid metabolites could function as endogenous endothelium-derived and zona glomerulosa-derived hyperpolarizing factors in the Adrenal cortex and contribute to the regulation of Adrenal Blood Flow.
Dino A Giussani - One of the best experts on this subject based on the ideXlab platform.
-
nitric oxide plays a role in the regulation of Adrenal Blood Flow and adrenocorticomedullary functions in the llama fetus
The Journal of Physiology, 2002Co-Authors: Raquel A Riquelme, Gina Sanchez, Leonel Liberona, Emilia M Sanhueza, Dino A Giussani, Carlos E Blanco, Mark A HansonAbstract:The hypothesis that nitric oxide plays a key role in the regulation of Adrenal Blood Flow and plasma concentrations of cortisol and catecholamines under basal and hypoxaemic conditions in the llama fetus was tested. At 0.6-0.8 of gestation, 11 llama fetuses were surgically prepared for long-term recording under anaesthesia with vascular and amniotic catheters. Following recovery all fetuses underwent an experimental protocol based on 1 h of normoxaemia, 1 h of hypoxaemia and 1 h of recovery. In nine fetuses, the protocol occurred during fetal i.v. infusion with saline and in five fetuses during fetal i.v. treatment with the nitric oxide synthase inhibitor l-NAME. Adrenal Blood Flow was determined by the radiolabelled microsphere method during each of the experimental periods during saline infusion and treatment with l-NAME. Treatment with l-NAME during normoxaemia led to a marked fall in Adrenal Blood Flow and a pronounced increase in plasma catecholamine concentrations, but it did not affect plasma ACTH or cortisol levels. In saline-infused fetuses, acute hypoxaemia elicited an increase in Adrenal Blood Flow and in plasma ACTH, cortisol, Adrenaline and norAdrenaline concentrations. Treatment with l-NAME did not affect the increase in fetal plasma ACTH, but prevented the increments in Adrenal Blood Flow and in plasma cortisol and Adrenaline concentrations during hypoxaemia in the llama fetus. In contrast, l-NAME further enhanced the increase in fetal plasma norAdrenaline. These data support the hypothesis that nitric oxide has important roles in the regulation of Adrenal Blood Flow and Adrenal corticomedullary functions during normoxaemia and hypoxaemia functions in the late gestation llama fetus.
Mark A Hanson - One of the best experts on this subject based on the ideXlab platform.
-
nitric oxide plays a role in the regulation of Adrenal Blood Flow and adrenocorticomedullary functions in the llama fetus
The Journal of Physiology, 2002Co-Authors: Raquel A Riquelme, Gina Sanchez, Leonel Liberona, Emilia M Sanhueza, Dino A Giussani, Carlos E Blanco, Mark A HansonAbstract:The hypothesis that nitric oxide plays a key role in the regulation of Adrenal Blood Flow and plasma concentrations of cortisol and catecholamines under basal and hypoxaemic conditions in the llama fetus was tested. At 0.6-0.8 of gestation, 11 llama fetuses were surgically prepared for long-term recording under anaesthesia with vascular and amniotic catheters. Following recovery all fetuses underwent an experimental protocol based on 1 h of normoxaemia, 1 h of hypoxaemia and 1 h of recovery. In nine fetuses, the protocol occurred during fetal i.v. infusion with saline and in five fetuses during fetal i.v. treatment with the nitric oxide synthase inhibitor l-NAME. Adrenal Blood Flow was determined by the radiolabelled microsphere method during each of the experimental periods during saline infusion and treatment with l-NAME. Treatment with l-NAME during normoxaemia led to a marked fall in Adrenal Blood Flow and a pronounced increase in plasma catecholamine concentrations, but it did not affect plasma ACTH or cortisol levels. In saline-infused fetuses, acute hypoxaemia elicited an increase in Adrenal Blood Flow and in plasma ACTH, cortisol, Adrenaline and norAdrenaline concentrations. Treatment with l-NAME did not affect the increase in fetal plasma ACTH, but prevented the increments in Adrenal Blood Flow and in plasma cortisol and Adrenaline concentrations during hypoxaemia in the llama fetus. In contrast, l-NAME further enhanced the increase in fetal plasma norAdrenaline. These data support the hypothesis that nitric oxide has important roles in the regulation of Adrenal Blood Flow and Adrenal corticomedullary functions during normoxaemia and hypoxaemia functions in the late gestation llama fetus.
Carlos E Blanco - One of the best experts on this subject based on the ideXlab platform.
-
nitric oxide plays a role in the regulation of Adrenal Blood Flow and adrenocorticomedullary functions in the llama fetus
The Journal of Physiology, 2002Co-Authors: Raquel A Riquelme, Gina Sanchez, Leonel Liberona, Emilia M Sanhueza, Dino A Giussani, Carlos E Blanco, Mark A HansonAbstract:The hypothesis that nitric oxide plays a key role in the regulation of Adrenal Blood Flow and plasma concentrations of cortisol and catecholamines under basal and hypoxaemic conditions in the llama fetus was tested. At 0.6-0.8 of gestation, 11 llama fetuses were surgically prepared for long-term recording under anaesthesia with vascular and amniotic catheters. Following recovery all fetuses underwent an experimental protocol based on 1 h of normoxaemia, 1 h of hypoxaemia and 1 h of recovery. In nine fetuses, the protocol occurred during fetal i.v. infusion with saline and in five fetuses during fetal i.v. treatment with the nitric oxide synthase inhibitor l-NAME. Adrenal Blood Flow was determined by the radiolabelled microsphere method during each of the experimental periods during saline infusion and treatment with l-NAME. Treatment with l-NAME during normoxaemia led to a marked fall in Adrenal Blood Flow and a pronounced increase in plasma catecholamine concentrations, but it did not affect plasma ACTH or cortisol levels. In saline-infused fetuses, acute hypoxaemia elicited an increase in Adrenal Blood Flow and in plasma ACTH, cortisol, Adrenaline and norAdrenaline concentrations. Treatment with l-NAME did not affect the increase in fetal plasma ACTH, but prevented the increments in Adrenal Blood Flow and in plasma cortisol and Adrenaline concentrations during hypoxaemia in the llama fetus. In contrast, l-NAME further enhanced the increase in fetal plasma norAdrenaline. These data support the hypothesis that nitric oxide has important roles in the regulation of Adrenal Blood Flow and Adrenal corticomedullary functions during normoxaemia and hypoxaemia functions in the late gestation llama fetus.