TY - JOUR
T1 - β-Adrenoceptor antagonist propranolol potentiates hypotensive action of natriuretic peptides
AU - Yoshimoto, Takanobu
AU - Naruse, Mitsuhide
AU - Ire, Kaoru
AU - Tanabe, Akiyo
AU - Seki, Toshirou
AU - Tanaka, Masami
AU - Imaki, Toshihiro
AU - Naruse, Kiyoko
AU - Muraki, Takamura
AU - Matsuda, Yuzuru
AU - Demura, Hiroshi
N1 - Funding Information:
This work was supported in part by research grants from the Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists; research grants from the Japanese Ministry of Education, Science, and Culture, the Kidney Foundation (Tokyo) for the research of the Kidney and NO, the SR Foundation (Tokyo), Grant-in-Aid from the Tokyo Hypertension Conference (Tokyo), and a research grant from Tanabe Biomedical Conference (Tokyo).
PY - 1998/6/12
Y1 - 1998/6/12
N2 - β-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 β-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 β-adrenoceptor antagonist propranolol.
AB - β-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 β-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 β-adrenoceptor antagonist propranolol.
KW - ANP receptor
KW - Hypertension
KW - Natriuretic peptide
KW - β-Adrenoceptor antagonist
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U2 - 10.1016/S0014-2999(98)00291-X
DO - 10.1016/S0014-2999(98)00291-X
M3 - Article
C2 - 9698206
AN - SCOPUS:0032511130
SN - 0014-2999
VL - 351
SP - 61
EP - 66
JO - European journal of pharmacology
JF - European journal of pharmacology
IS - 1
ER -