Vasoactive intestinal peptide in the regulation of renin secretion

We have previously shown that vasoactive intestinal peptide (VIP) is a renin-stimulating factor both in vivo and in vitro. In the present investigation we sought to determine whether VIP exerted this effect by a neural or humoral mechanism. To test for a neural effect, the renal nerves were stimulated on one side for 30 min in anesthetized dogs, and plasma VIP and renin levels were determined in the renal venous effluent. The stimulation significantly increased plasma renin activity in arterial and renal venous plasma but had no effect on VIP concentrations. A humoral action was tested in two ways. First, plasma renin activity was measured before and after elevating circulating levels of endogenously produced VIP using intravenous neostigmine (0.07 mg/kg) in control, renal-denervated, and propranolol-pretreated animals. In all three groups, the elevated plasma level of VIP was associated with a significant increase in plasma renin activity. Second, plasma levels of VIP were determined in conscious dogs with elevated plasma renin activity produced by either a low-salt diet or hemorrhage. In both cases, plasma renin activity was significantly elevated as expected, but plasma levels of VIP were unchanged. These data suggest that the effects of VIP on renin secretion are not mediated by release of the peptide from the renal nerves, the circulating level of endogenously produced VIP can be elevated sufficiently to stimulate renin secretion, but a humoral role of VIP in the elevated plasma renin activity produced by low-salt diet or hemorrhage seems unlikely.+