INHIBITORY EFFECTS OF NOREPINEPHRINE, METHOXAMINE AND PHENYLEPHRINE ON RENIN RELEASE FROM RAT-KIDNEY CORTICAL SLICES

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Abstract
The inhibition of renin release from rat kidney cortical slices by .alpha. adrenoceptor agonists was studied to determine if it is mediated by activation of .alpha.-1 and/or .alpha.-2 adrenoceptors, and the role of Ca in the mechanisms of this inhibition was also investigated. Norepinephrine (NE), methoxamine (ME) and phenylephrine (PE) produced a concentration-dependent inhibition of renin release from rat kidney cortical slices, whereas clonidine was without effect. NE-, ME- and PE-induced inhibition of renin release was blocked by prazosin, which was 2 or 3 orders of magnitude more potent than yohimbine. The inhibitory effects of NE, ME and PE on renin release from the slices were abolished by removal of Ca from the incubation medium. Ca antagonists, verapamil and nifedipine, attenuated the responses of renin release to NE, ME and PE, in a concentration-dependent manner. The inhibitory effects of NE, ME and PE on renin release were blocked significantly by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist, but not by N-(6-aminohexyl)-1-naphthalenesulfonamide, which had virtually no calmodulin antagonistic activity. Adrenoceptor agonists inhibit renin release from rat kidney cortical slices mainly via .alpha.-1 adrenoceptors and Ca influx followed by the activation of the Ca-calmodulin system is involved in the above inhibition.