Hemodynamic effects of carvedilol infusion and the contribution of the sympathetic nervous system in rats with heart failure

Yuichi Abe, Kenichi Watanabe, Shinji Sato, Yusuke Nagai, Fadia A. Kamal, Mir I.I. Wahed, Juan Wen, Gurusamy Narasimman, Meilei Ma, Palaniyandi Suresh, Toshihiro Takahashi, Hitoshi Tachikawa, Takeshi Kashimura, Naohito Tanabe, Makoto Kodama, Yoshifusa Aizawa, Kenichi Yamaguchi, Makoto Miyazaki, Masao Kakemi

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Abstract

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 (E max) 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.

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All Science Journal Classification (ASJC) codes

  • Pharmacology

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