Brain catecholamines mediate the delayed reduction in renin release after injection of fenfluramine.

The present studies examined whether brain or peripheral catecholaminergic mechanisms mediate the fenfluramine-induced reduction in plasma renin activity and concentration. Fenfluramine reduced plasma renin activity and concentration to 35% of basal levels in vehicle pretreated rats. This reduction was prevented in rats whose central catecholaminergic neurons were destroyed by i.c.v. injection of 6-hydroxydopamine (6-OHDA) two weeks prior to the experiment. In contrast, the suppressive effects of fenfluramine on plasma renin activity and concentration was not altered in rats that were surgically adrenal medullectomized and chemically sympathectomized by 6-OHDA. To determine whether alpha 2 adrenoceptors mediate the suppressive effects of fenfluramine, rats were pretreated with increasing doses of the alpha 2 adrenoceptor antagonist yohimbine 1 h before the administration of fenfluramine. Although yohimbine alone increased plasma renin activity and concentration, it did not prevent the suppressive effects of fenfluramine. In conclusion, the data suggest that central, but not peripheral catecholamines mediate the suppressive effect of fenfluramine on renin secretion. This effect is not mediated by alpha 2 adrenoceptors.

Stress-induced renin and corticosterone secretion is mediated by catecholaminergic nerve terminals in the hypothalamic paraventricular nucleus.

Cell bodies in the hypothalamic paraventricular nucleus (PVN) mediate stress-induced increases in renin and corticosterone secretion. Since the PVN has an extensive catecholaminergic innervation, we wanted to determine the role of catecholamines in the neuroendocrine response to stress. The stressor was a conditioned emotional (fear) response paradigm (CER). The catecholamine neurotoxin, 6-hydroxydopamine (6-OHDA), was injected into the PVN 14 days before the rats were subjected to the CER procedure. Damage to noradrenergic nerve terminals was verified immunocytochemically, using an antibody against dopamine beta-hydroxylase. Injection of 6-OHDa into the PVN prevented the stress-induced increase in plasma renin activity (PRA), plasma renin concentration (PRC) and plasma corticosterone concentration, suggesting that intact catecholaminergic innervation of neurons in the PVN is necessary for the stress-induced increase in renin and corticosterone secretion. To determine if beta-adrenoceptors in the PVN mediate the effect of stress on renin and corticosterone secretion, the beta-adrenoceptor antagonist sotalol was injected into the PVN through chronically implanted bilateral cannulae. The injection was performed on the 4th day of the CER paradigm, just before the rats were placed into the CER chamber. Sotalol prevented the stress-induced increase in corticosterone concentration, but did not diminish the stress-induced increase in PRA and PRC. These results suggest that the stress-induced increase in corticosterone concentration is influenced by beta-adrenoceptors in the PVN. The stress-induced increase in PRA and PRC is mediated by different receptors whose ligands might be catecholamines acting at non-beta-receptors or other neuroactive substances colocalized in catecholaminergic nerve terminals.

A comparison of acute stress paradigms: hormonal responses and hypothalamic serotonin.

The effects of stress on plasma renin activity (PRA), plasma prolactin and corticosterone levels, and hypothalamic 5-HT and 5-HIAA concentrations were investigated using a 3 and 12 min conditioned fear (CER) paradigm; 20 min immobilization; 20 min exposure to shallow or deep cold water; 2, 12 and 22 min of intermittent footshock with or without 20 min recovery; and, a 3 min CER with 0, 10, 30 and 60 min recovery. PRA was increased by all the stressors, except shallow cold water, reaching a maximum after 12 min and returning to control values within 10-20 min post-stress. Prolactin levels also were increased by all the stressors, except shallow and deep cold water. Prolactin levels were maximal after 12 min and returned to baseline within 20-60 min post-stress, depending on the stressor. Corticosterone levels were elevated by all the stressors, but not as rapidly as PRA or prolactin, reaching a maximum after about 20 min and returning to baseline concentrations within 30-60 min post-stress. None of the stressors produced significant changes in hypothalamic 5-HT and 5-HIAA concentrations.

Serotonergic regulation of the release of renin is not mediated by the autonomic nervous system but involves beta adrenoceptors.

p-Chloroamphetamine (PCA) which releases serotonin is known to increase the activity of plasma renin in conscious rats by stimulating serotonergic neurotransmission in the brain. The present studies were designed to investigate whether this effect is mediated from the serotonin receptors in the brain to the kidneys via the sympathetic nervous system. The effect of PCA on the activity of plasma renin was completely blocked by the beta receptor blockers sotalol and atenolol, but was not prevented by the sympathetic inhibitor, bretylium tosylate. In additional studies, chemical sympathectomy with 6-hydroxydopamine, combined with adrenal medullectomy did not prevent the effect of PCA on the activity of plasma renin even though the renal content of norepinephrine was reduced to undetectable levels. Furthermore, complete transection of the spinal cord between the first and second thoracic vertebrae did not prevent the effect of PCA on the activity of plasma renin, suggesting that the sympathetic nervous system and adrenal catecholamines do not mediate the effect of PCA. Studies by others have suggested that extrarenal beta receptors play an important role in the regulation of secretion of renin. The results of the present study support this possibility. The role of the parasympathetic nervous system in the rise in the activity of plasma renin induced by PCA was investigated by pretreatment of the rats with the peripheral muscarinic receptor blocker, methyl atropine.(ABSTRACT TRUNCATED AT 250 WORDS)