Hemodynamic effects of carvedilol infusion and the contribution of the sympathetic nervous system in rats with heart failure.
We investigated the contribution of the sympathetic nervous system (SNS) in maintaining the blood pressure and in regulating the cardiac function during and after carvedilol administration in rats with heart failure (group F). Left ventricular end-diastolic pressure, percent functional shortening, and rates of intraventricular pressure rise were significantly changed by carvedilol infusion as compared with the basal values in group N (normal rats), but not in group F. The left ventricular end-diastolic pressure was elevated, corresponding to the enhancement of the plasma norepinephrine (NE) concentration caused by carvedilol infusion, in group N. The enhancement of the plasma NE concentration induced by carvedilol administration in group F was higher than that in group N. The value for the maximal hypertensive effect of NE intravenous infusion (Emax) was decreased, and the plasma NE concentration at half-maximal effect (EC50) was increased in group F as compared with the values in group N. These results indicate that the SNS (presynaptic) activity is increased and that the SNS receptor sensitivity in the cardiovascular regulation system is decreased in heart failure.
Abe
Yuichi
Y
Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Kamishinei-cho, Japan.
Watanabe
Kenichi
K
Sato
Shinji
S
Nagai
Yusuke
Y
Kamal
Fadia A
FA
Wahed
Mir I I
MI
Wen
Juan
J
Narasimman
Gurusamy
G
Ma
Meilei
M
Suresh
Palaniyandi
P
Takahashi
Toshihiro
T
Tachikawa
Hitoshi
H
Kashimura
Takeshi
T
Tanabe
Naohito
N
Kodama
Makoto
M
Aizawa
Yoshifusa
Y
Yamaguchi
Kenichi
K
Miyazaki
Makoto
M
Kakemi
Masao
M
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000465:Algorithms; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology*; D000077261:Carvedilol; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D009638:Norepinephrine