BETA-ADRENOCEPTOR ANTAGONIST PROPRANOLOL POTENTIATES HYPOTENSIVE ACTION OF NATRIURETIC PEPTIDES

beta-Adrenoceptor antagonists are known to increase plasma atrial natr iuretic peptide (ANP) levels despite their hypotensive action. The aim of the present study was to examine the role of the ANP system in the antihypertensive effects of a beta-adrenoceptor antagonist. We invest igated the effects of propranolol (75 mg kg(-1) day(-1), p.o., 4 weeks ) on the ANP system in stroke-prone spontaneously hypertensive rats. P lasma ANP levels were significantly higher in the propranolol group th an in the control group. Both receptor densities and mRNA levels of AN P(C) receptor were significantly decreased in the lung as the major si te of ANP clearance from the circulation. In contrast, both central ve nous pressure and ANP mRNA levels in the heart were not significantly different between the two groups. Under both basal and ANP-stimulated conditions, the cGMP content in the aorta was significantly greater in the propranolol group than in the control group, whereas the basal an d stimulated cGMP content of the kidney was similar in the two groups. Inhibition of endogenous ANP action by a specific ANP receptor antago nist, HS-142-1, produced a greater increase of blood pressure in the p ropranolol group than in the control group. These results suggest pote ntiation of natriuretic peptide activity as a new antihypertensive mec hanism of the beta-adrenoceptor antagonist propranolol. (C) 1998 Elsev ier Science B.V. All rights reserved.