Inhibitory effects of AE0047, a new dihydropyridine Ca2+ channel blocker, on renal nerve stimulation-induced renal actions in anesthetized dogs

The effects of AE0047, a newly developed dihydropyridine Ca2+ channel block er, and nicardipine on changes in the renal function and norepinephrine (NE ) overflow induced by renal nerve stimulation (RNS) were examined in anesth etized dogs. RNS at a low frequency (0.5-2.0 Hz) caused significant decreas es in the urine flow, urinary excretion of sodium, and fractional excretion of sodium, while also inducing increases in the NE secretion rate (NESR), without affecting the renal hemodynamics. RNS at a high frequency (2.5-5.0 Hz), which diminishes the renal bloodflow, glomerular filtration rate, and filtrate fraction, elicited more potent decreases in urine formation and in creases in NESR than those seen for the low-frequency RNS. When AE0047 (10 and 50 ng/kg/min) was administered intrarenally, increases in the basal ren al blood flow and urine formation were observed. During AE0047 (50 ng/kg/mi n) infusion, low-frequency RNS-induced antidiuretic action and increase in NESR were markedly attenuated. Qualitatively similar results were observed for high-frequency RNS. In addition, high-frequency RNS-induced renal vasoc onstriction was significantly suppressed by AE0047 infusion at higher doses . Lower doses of AE0047 (10 ng/kg/min) tended to attenuate the low- and hig h-frequency RNS-induced antidiuretic actions, although neither of the RNS-i nduced increases in NESR were suppressed by lower doses of AE0047. Nicardip ine (50 ng/kg/min) also increased the level of basal urine formation, but t he RNS-induced changes in renal function and increases in NESR were not aff ected by this drug. These results suggest that AE0047 suppresses the RNS-in duced NE overflow from renal nerve endings, which is probably involved in t he inhibitory effects of the drug on the antidiuretic action elicited by RN S.