Carvedilol enhances atrial and brain natriuretic peptide mRNA expression and release in rat heart.
To clarify the role of the natriuretic peptide (NP) system in the myocardial protective effects of carvedilol, a beta-blocking agent, we investigated the effects of carvedilol on the NP system in the rat heart. After oral administration of carvedilol (low-dose group: 2 mg/kg/day, group C2; high-dose group: 20 mg/kg/day, group C20) for 1 week, plasma rat atrial NP (r-ANP), atrial mRNA levels of ANP, left ventricular mRNA of brain NP (BNP), NP receptor-A and NP receptor-C (NPR-C) (as a clearance receptor) were measured. Values were compared with those in vehicle-treatment rats (group V). The concentration of r-ANP was significantly higher in group C2 (135 +/- 9 pg/ml) and group C20 (161 +/- 11 pg/ml) than group V (75 +/- 6 pg/ml; both p < 0.01). ANP and BNP mRNA levels were significantly increased and NPR-C was significantly down regulated in group C2 (151 +/- 7, 120 +/- 8 and 78 +/- 7%, respectively, vs. group V) and group C20 (164 +/- 8. 133 +/- 7 and 72 +/- 8%, respectively, vs. group V) compared with group V (all p < 0.01). These results suggest that not only a high dose, but a low dose of carvedilol has the effect of increasing plasma ANP and BNP levels. This effect was closely related to the upregulation of ANP and BNP mRNA expression, and the down regulation of NPR-C mRNA expression in the heart. These mechanisms seem to account for a sizable portion of the protective effect of carvedilol for heart diseases.
Ohta
Y
Y
Department of Clinical Pharmacology, Niigata College of Pharmacy, Japan.
Watanabe
K
K
Nakazawa
M
M
Yamamoto
T
T
Ma
M
M
Fuse
K
K
Ito
M
M
Hirono
S
S
Tanabe
T
T
Hanawa
H
H
Kato
K
K
Kodama
M
M
Aizawa
Y
Y
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D006162:Guanylate Cyclase / Q000235:genetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000235:genetics* / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011917:Rats, Inbred Lew; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics
D000319:Adrenergic beta-Antagonists; D000975:Antioxidants; D002227:Carbazoles; D011412:Propanolamines; D012333:RNA, Messenger; D000077261:Carvedilol; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; C073616:atrial natriuretic factor receptor C