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Effects of K-351 on Adrenergically Induced Renin Release and Renal Vasoconstriction in Anesthetized Dogs

Summary: Effect of 3–4-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)- 3-nitroxy-2H-1 -benzopyran (K-351) infused into the renal artery on renin release during graded renal nerve stimulation (RNS) was investigated in pentobarbital-anesthetized dogs. K-351 (20 µg/min) produced significant suppression of the RNS-induced renin release; the renin secretion responses to RNS at lower frequencies (0.5 and 1 Hz) were almost abolished, and those at the highest frequency (3 Hz) were attenuated. K-351 also suppressed an increase in renal vascular resistance during RNS at 3 Hz. The same extent of inhibition in the renin secretion response to RNS was also obtained during infusion of DL-propranolol (100 µg/min). Inhibitory effect of K-351, prazosin, or phentolamine on the renal vasoconstriction induced by RNS and norepinephrine (NE) injected into the renal artery, an ˜50% reduction in renal blood flow, was also assessed. K-351 and prazosin exerted a greater inhibitory effect on RNS- than on NE-induced vasoconstriction, and the opposite was true of phentolamine. The potency of K-351 in reducing the vasoconstriction due to RNS or NE was roughly estimated to be 10–30 times less than that of prazosin. These results suggest that K-351 shares β- and α-adrenoceptor blocking properties, which effectively contribute to the suppression of adrenergically induced renin release and renal vasoconstriction.