Pharmacological Evidence that Stimulation of Central Serotonergic Pathways Increases Renin Secretion

Zimmermann, Heinz; Ganong, William F.

doi:10.1159/000122983

Cited by 43 publications

(11 citation statements)

References 16 publications

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“…It is noteworthy that amphetamine releases NE from neurons and increases blood pressure (Weiner, 1989). The fact that (Ϯ)-fenfluramine, which releases NE via its metabolite (Ϯ)-norfenfluramine, does not increase blood pressure is probably because rapid and simultaneous elevations of synaptic 5-HT produce an overall re- duction in blood pressure (Zimmermann and Ganong, 1980;Ramirez et al, 1982;Itskovitz et al, 1989). Viewed collectively, the present results emphasize the complex pharmacology of (Ϯ)-fenfluramine.…”

Section: Discussionmentioning

confidence: 52%

(+)-Fenfluramine and Its Major Metabolite, (+)-Norfenfluramine, Are Potent Substrates for Norepinephrine Transporters

Rothman

Clark²,

Partilla³

et al. 2003

J Pharmacol Exp Ther

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(Ϯ)-Fenfluramine is an amphetamine analog that was once widely prescribed as an appetite suppressant. Although (Ϯ)-fenfluramine is no longer clinically available, the mechanisms underlying its anorectic properties are still of interest. Upon peripheral administration, stereoisomers of (Ϯ)-fenfluramine are N-deethylated to form the metabolites, (ϩ)-and (Ϫ)-norfenfluramine. It is well accepted that isomers of (Ϯ)-fenfluramine and (Ϯ)-norfenfluramine interact with 5-hydroxytryptamine (serotonin, 5-HT) transporters to release 5-HT from neurons. However, the effects of these drugs on other monoamine transporters are not well characterized. In this study, we examined the interaction of stereoisomers of (Ϯ) Results from in vivo microdialysis experiments showed that intravenous injection of (ϩ)-norfenfluramine elevates extracellular levels of 5-HT, NE, and DA in rat frontal cortex. The effects of (ϩ)-norfenfluramine on NE and DA were antagonized by pretreatment with the NE uptake blocker nisoxetine. In summary, administration of fenfluramines can increase synaptic levels of 5-HT, NE, and DA in the cortex, and (ϩ)-norfenfluramine likely contributes to these effects. Release of NE and DA evoked by (ϩ)-norfenfluramine is at least partly mediated via NE transporters. Our results emphasize the potential involvement of noradrenergic mechanisms in the actions of fenfluramines.

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Section: Discussionmentioning

confidence: 52%

(+)-Fenfluramine and Its Major Metabolite, (+)-Norfenfluramine, Are Potent Substrates for Norepinephrine Transporters

Rothman

Clark²,

Partilla³

et al. 2003

J Pharmacol Exp Ther

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“…Most of the dogs in the present study were part of an investiga tion of central serotonergic effects on renin secretion, and the paper reporting these results provides details of the experimental proto cols [18]. Mongrel dogs of either sex, weighing 11-30 kg.…”

Section: Methodsmentioning

confidence: 99%

“…were anesthetized with sodium pentobarbital (30 mg/kg i.v., with addi tional pentobarbital as needed to maintain anesthesia). The abdo men was opened through a flank incision and a Blalock clamp placed around the aorta proximal to the renal arteries to maintain the renal perfusion pressure constant [18],The drugs used in this portion of the study were ¿-tryptophan (ICN Pharmaceuticals. Plainview.…”

mentioning

confidence: 99%

Evidence that the Effects of 5-Hydroxytryptophan on the Secretion of ACTH and Growth Hormone in Dogs are not Mediated by Central Release of Serotonin

Zimmermann¹,

Kaplan²,

Ganong³

1982

Neuroendocrinology

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5-Hydroxytryptophan (5-HTP) was found to lower plasma 11-oxycorticoids and increase plasma growth hormone in anesthetized dogs. To determine whether these effects were mediated by release of serotonin, 5-HTP and L-tryptophan were injected intravenously alone and after treatment with various drugs. The decrease in corticoids produced by 5-HTP was unaffected by intravenous carbidopa and metergoline, but was abolished by intravenous benserazide in a dose that inhibits central 5-HTP and dopa decarboxylase, and by a small dose of phenoxybenzamine in the third ventricle. Adrenal sensitivity to ACTH was unaffected by 5-HTP. L-Tryptophan did not decrease plasma corticoids; instead it produced a small increase. The increase in plasma growth hormone produced by 5-HTP was potentiated by carbidopa and abolished by benserazide. L-Tryptophan did not increase plasma growth hormone; instead it produced no change or in some instances a decrease. Plasma growth hormone declined after administration of phenoxybenzamine in the third ventricle, and the decline continued after administration of 5-HTP. The data indicate that the effects of 5-HTP on ACTH and growth hormone secretion are not due to central release of serotonin and suggest that they are due instead to serotonin-induced release of catecholamines from catecholamine-secreting neurons.

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“…PRA is elevated after immobilization, handling, and head-up tilt in rats, and arithmetic or intelligence quotient tests in humans (5)(6)(7)(8)(9)(10). The mechanism by which PRA increases in response to acute stress involves sympathetic activation, since the increases are attenuated by renal denervation and ,3-adrenergic blockers (5,11,12).…”

Section: Introductionmentioning

confidence: 99%

Hyperreninemic hypoaldosteronism after chronic stress in the rat.

Aguilera¹,

Kiss²,

Sunar-Akbasak³

1995

J. Clin. Invest.

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The effects of chronic stress on the renin-angiotensin-aldosterone system were studied by analysis of plasma hormone levels, kidney renin mRNA levels, adrenal angiotensin II receptors, and steroidogenesis in rats subjected to repeated immobilization (2 h daily) or intraperitoneal injections of 1.5 M NaCl for 14 d. 24 h after the last stress in both stress models, plasma aldosterone levels were reduced in spite of significant increases in plasma renin activity. Repeatedly intraperitoneal hypertonic saline-injected rats showed plasma renin activity responses to acute immobilization similar to controls, but markedly reduced plasma aldosterone responses. Concomitant with the increases in plasma renin activity, renin mRNA levels in the kidney were significantly increased in intraperitoneal hypertonic saline-injected rats, and these increases were prevented by ,B-adrenergic receptor blockade with propranolol. In isolated adrenal glomerulosa cells from chronically stressed rats, maximum aldosterone responses to angiotensin II, ACTH, and 8-Br-cAMP were significantly decreased, whereas pregnenolone responses were increased. P450-aldosterone synthetase mRNA levels and binding of '"I-[Sar',Ile8]angiotensin II were significantly reduced in the adrenal zona glomerulosa of stressed rats. These studies show that chronic repeated stress leads to renin stimulation due to sympathetic activation, and inhibition of aldosterone secretion due to inhibition of the late steroidogenic pathway. The data provide evidence for a role of chronic stress in the development of hyperreninemic hypoaldosteronism. (J. Clin. Invest. 1995. 96:1512-1519

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Pharmacological Evidence that Stimulation of Central Serotonergic Pathways Increases Renin Secretion

Cited by 43 publications

References 16 publications

(+)-Fenfluramine and Its Major Metabolite, (+)-Norfenfluramine, Are Potent Substrates for Norepinephrine Transporters

(+)-Fenfluramine and Its Major Metabolite, (+)-Norfenfluramine, Are Potent Substrates for Norepinephrine Transporters

Evidence that the Effects of 5-Hydroxytryptophan on the Secretion of ACTH and Growth Hormone in Dogs are not Mediated by Central Release of Serotonin

Hyperreninemic hypoaldosteronism after chronic stress in the rat.

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