Intrinsic Sympathomimetic Activity Counteracts Beta-Blocker Inhibition of Renin Activation

Michael C. Ruddy, Grace B. Bialy, John B. Kostis

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Enzymatically inactive renin (IR) is the predominant circulating form of renin. Sympathetic activity may influence plasma renin activity (PRA) by regulation of the conversion of IR to active renin (AR, PRA). It has been demonstrated previously that beta blockade lowers PRA at least partly through inhibition of this conversion process. The authors hypothesized that beta blockade and intrinsic sympathomimetic activity (ISA) would have opposing effects on production of AR from its inactive precursor.Eighteen primary hypertensives (12 male, 6 female, mean age 57.7 ± 2.7) were entered in a placebo-controlled, double-blind crossover study of the effects of equipotent doses of pindolol and propranolol on mean ± SEM systolic BP, diastolic BP, heart rate, active renin (AR), total renin (TR), inactive renin (IR), and % AR/TR. Drug dose was titrated to achieve a goal DBP of 90 mmHg or less. Active renin was defined as the rate of generation of angiotensin I in 37°C plasma at pH 5.7. Total renin was determined by preincubation of plasma aliquots with 1.5 mg/mL trypsin in the presence of 5 mM benzamadine for one hour at -4°C prior to assay of renin activity. Inactive renin was calculated as TR minus AR.The BP responses achieved by dose titration of propranolol and pindolol were virtually identical at rest, indicating equivalent depressor effects of the two beta blockers. Heart rate and active renin were, however, lowered to a much greater extent with propranolol as compared with pindolol. The lack of significant pindolol-induced fall in % AR/TR suggests that this drug has little net effect on the formation of AR from IR. These findings indicate that the presence of ISA attenuates the inhibitory action of beta blockade on AR. This effect may be a result of ISA-mediated partial disinhibition of conversion of inactive prorenin at renal or extrarenal sites.

Original languageEnglish (US)
Pages (from-to)45-50
Number of pages6
Issue number1
StatePublished - Jan 1989

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine


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