Role of endothelins in regulation of vascular tone  in the in situ perfused rat adrenals

Mazzocchi, Giuseppina; Malendowicz, Ludwik K.; Musajo, F; Gottardo, Giuseppe; Markowska, Anna; Nussdorfer, Gastone G.

doi:10.1152/ajpendo.1998.274.1.e1

Cited by 10 publications

(13 citation statements)

References 24 publications

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“…Endothelin was released in response to an increase in perfusion flow rate, while exogenous administration of ET caused a decrease in vascular perfusion. 12 In a similar study, Mazzocchi et al 49 showed that ET infusion causes a decrease in flow rate of the perfusion medium. Using specific antagonists for ET A and ET B receptors, they demonstrated that the decrease in flow rate was a result of ET A receptor activation, which required protein kinase C activation.…”

Section: Mechanisms By Which Et May Affect Adrenal Functionmentioning

confidence: 86%

Endothelin Regulation of Adrenal Function

Hinojosa‐Laborde

Lange

1999

Clin Exp Pharma Physio

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1. The goal of the present review is to recount the evidence that endothelin (ET) has a significant influence on the peripheral sympathetic nervous system by regulating the function of the adrenal medulla. 2. The presence of an active ET system in the adrenal medulla has been clearly demonstrated. Endothelin protein, mRNA, binding sites and ET-converting enzyme have been identified in adrenal tissue and medullary chromaffin cells, suggesting that this peptide may contribute to the regulation of adrenal medullary function. 3. Studies investigating the function of ET in the adrenal gland have demonstrated that ET has a stimulatory effect on the adrenal medulla. Endothelin elicits an increase in catecholamine release from perfused intact adrenal glands as well as from cultured chromaffin cells. This effect has been shown to be mediated by ETA and ETB receptors. 4. The mechanism by which ET causes an increase in catecholamine release from the adrenal medulla appears to be independent of cholinergic activation of chromaffin cells. Endothelin has been shown to act directly at chromaffin cells to increase intracellular calcium, which results in catecholamine release. 5. Endothelin can indirectly affect catecholamine release by its effect on adrenal blood flow. Studies indicate that ET has both vasoconstrictor and vasodilator effects in the adrenal gland, which suggests a role for ET in the regulation of adrenal blood flow. Endothelin has also been proposed to participate in the selective contraction of the adrenomedullary veins, which enhances the discharge of catecholamines from the adrenal gland during activation.

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Section: Mechanisms By Which Et May Affect Adrenal Functionmentioning

confidence: 86%

Endothelin Regulation of Adrenal Function

Hinojosa‐Laborde

Lange

1999

Clin Exp Pharma Physio

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“…Thus, ET stimulates cortisol and aldosterone secretion directly and by enhancing ACTH action. Together with nitric oxide (NO) it regulates the adrenal vascular tone and stimulates adrenal growth (7,8). It was demonstrated that glucocorticosteroids induce ET release by vascular smooth muscle cells, suppress the activity of the NO system and thus cause vasoconstriction, endothelial dysfunction and atherosclerosis (9).…”

Section: Introductionmentioning

confidence: 99%

Elevated plasma endothelin as an additional cardiovascular risk factor in patients with Cushing's syndrome

Кirilov¹,

Tomova²,

Dakovska³

et al. 2003

European Journal of Endocrinology

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Background: Recently the pathophysiological role of endothelin (ET) has been presumed in a number of adrenal disorders such as primary hyperaldosteronism, pheochromocytoma and adrenocortical insufficiency. Aim: The aim of the present study was to evaluate circulating ET-1 levels in patients with endogenous Cushing's syndrome. Methods and results: Plasma ET-1 levels were determined by highly sensitive RIA. Thirteen untreated subjects with Cushing's syndrome were studied: eight women and five men of mean age 44.2^9.5 years (S.D.). In ten of them, Cushing's disease had been diagnosed and three had adrenal adenomas. ET-1 was 3-fold higher in the patient group than in age-matched healthy controls (n ¼ 13): 1.59^0.78 vs 0.46^0.20 pmol/l respectively, P , 0.001. In adrenal adenoma patients, ET-1 was not significantly higher than in the Cushing's disease subjects (1.84^0.67 vs 1.51^0.83 pmol/l respectively, P . 0.05). In three patients who died of severe cardiovascular complications, plasma ET-1 was significantly higher than in the remaining patients (2.34^0.35 pmol/l, P , 0.05). A positive correlation was found between the total cholesterol (6.94^1.75 mmol/l) and ET-1 levels in the patients with Cushing's syndrome: r ¼ þ0.73, P , 0.02. No correlation was observed, however, between the levels of ET-1 and blood pressure (183^37/106^18 mmHg), plasma cortisol levels (455.2^74.5 nmol/l) or urinary cortisol excretion (1463^726 nmol/24 h). The successful treatment and correction of hypercortisolism in seven patients led to insignificant reduction in plasma ET from 1.34^0.69 to 0.73^0.53 pmol/l, P . 0.05. Conclusion: Our results clearly demonstrate that the ET system is activated in Cushing's syndrome. Elevated plasma ET-1 levels probably play a role in the pathogenesis of accelerated and early atherosclerosis development in this disorder.

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“…In effect, ETs regulate vascular tone in in situ perfused rat adrenal gland, via both protein kinase C-coupled ET A and NOS-ET B receptors, whose activation evokes vasoconstriction and vasodilation, respectively (Mazzocchi et al, 1998). Probably, ET-induced activation of ET B receptors is modulated by endothelium-derived nitric oxide.…”

Section: Discussionmentioning

confidence: 98%

Endothelin Signaling Pathways in Rat Adrenal Medulla

Israel¹,

Mathison

Rosario³

2006

Cell Mol Neurobiol

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1. We further characterized the effect of endothelins (ETs) on receptor-mediated phosphoinositide (PI) turnover, nitric oxide synthase (NOS) activation, and cGMP formation in whole rat adrenal medulla. 2. The PI hydrolysis was assessed as accumulation of inositol monophosphates (InsP(1)) in the presence of 10 mM LiCl in whole tissue and the analysis of inositol-1-phosphate by Dowex anion exchange chromatography. NOS activity was assayed by monitoring the conversion of radiolabeled L-arginine to L-citrulline. Cyclic GMP formation was assessed as accumulation of cGMP in whole tissue in the presence of phosphodiesterase inhibition, and the amount of cGMP formed was determined by radioimmuno-antibody procedure. 3. ET-1 and ET-3 increased PI turnover by 30% in whole adrenal medulla prelabeled with [(3)H] myoinositol. Both ETs isoforms, at equimolar doses, increased NOS activity and cGMP levels in similar degree. The selective ET(B) receptor agonist, IRL-1620, also increased cGMP formation, mimicking the effects of ETs, while IRL-1620 did not alter the PI metabolism. ETs-induced InsP(1) accumulation and cGMP was dependent on extracellular calcium. The effect of ETs on PI turnover was inhibited by neomycin. The L-arginine analogue, N-nitro-L-arginine (L-NAME), and two inhibitors of soluble guanylyl cyclase, methylene blue and ODQ, significantly inhibited the increase in cGMP production induced by ETs or IRL-1620. The selective ET(A) receptor antagonist, BQ 123, inhibited the ETs-induced increase in PI turnover, while the selective ET(B) receptor antagonist, BQ 788, was ineffective. Likewise, BQ 788, significantly inhibited ET-1- or ET-3-induced NOS activation and cGMP generation but not ETs-induced InsP(1) accumulation. 4. Our data indicate that stimulation of PI turnover and NO-induced cGMP generation constitutes ETs signaling pathways in rat adrenal medulla. The former action is mediated through activation of ET(A) receptor, while the latter through the activation of ET(B) receptor. These results support the role of endothelins in the regulation of adrenal medulla function.

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Role of endothelins in regulation of vascular tone in the in situ perfused rat adrenals

Cited by 10 publications

References 24 publications

Endothelin Regulation of Adrenal Function

Endothelin Regulation of Adrenal Function

Elevated plasma endothelin as an additional cardiovascular risk factor in patients with Cushing's syndrome

Endothelin Signaling Pathways in Rat Adrenal Medulla

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