Various endogenous neurotransmitter systems have been shown to take part in central regulation of renal function through the medium of intracellular cAMP, a second messenger of cellular events in response to activation of membrane receptors. This study was undertaken to observe further the influence of adenylate cyclase activation, leading to increased cAMP levels, on the central regulation of renal function.
Forskolin, an activator of adenylate cyclase, was administered into a lateral ventricle (icv) of rabbit brain in doses ranging from 13 to 130 ㎍/㎏ and changes in renal function were observed. With 13 ㎍/㎏ icv no marked changes in renal function were noted. Tripling the does to 40 ㎍/㎏ icv produced marked increases in urine flow rate and excretory rate of Na and K along with increased renal perfusion (=C_(Na)) and the fraction of sodium excreted (=FE_(Na)). Increasing the does further up to 130 ㎍/㎏ icv elicited marked diuresis, natriuresis and kaliuresis for about 20 min, with increased renal hemodynamics. The fraction of filtered sodium excreted (=FE_(Na)), indicative of the degree of inhibition of tubular sodium reabsorption, also increased. No significant changes in systemic pressure were noted.
DMSO, the solvent employed to dissolve forskoin, given icv in 0.15㎖ up to the concentration of 63%, did not produce significant diuresis, natriuresis, kaliuresis, nor any significant changes in systemic blood pressure. Therefore, forskolin was dissolved in 63% DMSO.
When given intravenously, however, forskolin 130 ㎍/㎏, a dose which elicits marked diuresis and natriuresis when given icv, did not produce diuretic effect, but rather tended to decrease urinary output and sodium excretion, implicating central mechanism of the icv effect. In preparations in which one kidney was denervated, with the other serving as control, the denervated kidney responded to icv forskolin with more prominent diuresis and natriuresis, suggesting humoral mediation of the effect. Plasma levels of ANP significantly increased, up to more than double the control level at 20 min after 130 ㎍/㎏ forskolin icv, when the natriuresis reached the peak.
These observations suggest that endogenously produced cAMP, by activating adenylate cyclase cause the renal effects, mediated by ANP, and indicate that the adenylate cyclase-cAMP system in involved in central regulation of renal function.
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