The preferential alpha 2-adrenergic antagonist yohimbine (4 mg/kg s.c.) caused a time-related increase in serum renin activity and heart rate in conscious Sprague-Dawley rats. Although mean arterial pressure was not decreased significantly over the 2-h period, heart rate was elevated significantly at 15 and 30 min post-injection. In contrast, serum renin activity remained elevated for up to 2 h with a 9-fold and 9.7-fold increase occurring at 30 and 60 min post-injection, respectively. Yohimbine (0.3, 1, 3 and 10 mg/kg s.c.) elicited a dose-related increase in serum renin activity and heart rate (30 min post-injection). The 1 mg/kg dose of yohimbine did not alter blood pressure whereas the 3 mg/kg dose caused a variable decrease in mean arterial pressure. The highest dose of yohimbine (10 mg/kg) significantly lowered blood pressure. The beta-adrenergic receptor antagonist propranolol (1.5 mg/kg s.c.), blocked the renin release and tachycardia caused by yohimbine (1 and 3 mg/kg s.c.), and the ganglionic blocking agent chlorisondamine partially inhibited the renin release elicited by 3 mg/kg (s.c.) of yohimbine. The prostaglandin synthetase inhibitors indomethacin (5 mg/kg s.c.) and meclofenamate (5 mg/kg s.c.) impaired the ability of yohimbine (3 mg/kg) to elevate SRA but did not alter the hemodynamic effects of yohimbine. Thus, the increase in renin release caused by yohimbine appears to be mediated by the sympathetic nervous system. Because the smaller doses of yohimbine increase renin release in the absence of a decrease in mean arterial pressure, it is unlikely that yohimbine stimulates renin release by baroreflex-mediated activation of the renal sympathetic nerves.(ABSTRACT TRUNCATED AT 250 WORDS)