The dominance of adrenergic mechanisms in mediating hypotensive drug-induced renin release in the conscious rat

The role of the sympathetic neuronal, the renal baroreceptor and the macula densa mechanisms in increasing renin release during drug-induced hypotension was investigated in the conscious rat. The alpha adrenergic antagonist phentolamine (which reflexly increases heart rate) and the ganglionic blocking agent chlorisondamine (which causes bradycardia) were used as representatives of two classes of vasodepressor drugs that have opposite effects on peripheral sympathetic nerve activity. In equihypotensive doses, phentolamine caused a much greater increase in serum renin activity than did chlorisondamine. Pretreatment of rats with the beta adrenergic antagonist propranolol impaired 90% of the renin release and all of the tachycardia caused by phentolamine without altering the decrement in blood pressure caused by phentolamine. Propranolol did not block the increment in serum renin activity elicited by chlorisondamine. In addition, chlorisondamine prevented the majority of the renin release caused by phentolamine. Salt loading by treatment with deoxycorticosterone acetate and saline drinking water blunted the hypotensive effects of phentolamine and chlorisondamine, but did not impair their ability to increase heart rate or serum renin activity. When our previously published data obtained with other hypotensive drugs were combined with the data presented here, a close correlation was found between the ability of a vasodepressor agent to increase heart rate and its ability to increase renin secretion. We conclude that the renin release caused by a drug-induced decrement in blood pressure in the conscious rat is almost entirely dependent on reflex activation (via the carotid baroreceptor mechanism) of the renal sympathetic nerves. Conversely, the decrement in renal perfusion pressure sensed by the afferent arteriolar baroreceptor contributes minimally to this renin release.