Beta-adrenoceptor antagonist propranolol potentiates hypotensive action of natriuretic peptides.
Beta-adrenoceptor antagonists are known to increase plasma atrial natriuretic 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 investigated the effects of propranolol (75 mg kg(-1) day(-1), p.o., 4 weeks) on the ANP system in stroke-prone spontaneously hypertensive rats. Plasma ANP levels were significantly higher in the propranolol group than in the control group. Both receptor densities and mRNA levels of ANP(C) receptor were significantly decreased in the lung as the major site of ANP clearance from the circulation. In contrast, both central venous 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 and stimulated cGMP content of the kidney was similar in the two groups. Inhibition of endogenous ANP action by a specific ANP receptor antagonist, HS-142-1, produced a greater increase of blood pressure in the propranolol group than in the control group. These results suggest potentiation of natriuretic peptide activity as a new antihypertensive mechanism of the beta-adrenoceptor antagonist propranolol.
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Japan. rxk00525@niftyserve.or.jp
T
T
Yoshimoto
M
M
Naruse
K
K
Irie
A
A
Tanabe
T
T
Seki
M
M
Tanaka
T
T
Imaki
K
K
Naruse
T
T
Muraki
Y
Y
Matsuda
H
H
Demura
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000032:analysis; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D011134:Polysaccharides / Q000494:pharmacology; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D017461:Receptors, Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; C072551:HS 142-1; D011134:Polysaccharides; D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor; D011433:Propranolol; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP