Acute Effect of Endothelin AB Antagonist on Sympathetic Outflow in Conscious Rats With Heart Failure

Abstract

Although ET-1 antagonists have been beneficial in the treatment of heart failure (HF), their involvement in the effect on the sympathetic nervous system in HF remains unknown. The present study investigated the role of endogenous endothelin (ET) in the sympathetic nervous system in HF by observing the effect of ET AB antagonist (TAK-044) on renal sympathetic nerve activity (RSNA) in conscious rats with HF (n=7). HF was induced by left coronary artery ligation and 6 weeks later, TAK-044 was intravenously administered in the conscious and freely moving rats. RSNA, mean arterial pressure (MAP) and heart rate were compared with rats with sham operations (sham; n=7). MAP was significantly decreased in both groups; however, RSNA was significantly decreased only in the HF group at 5 min after administration, and this change continued until 10 min. There was also an effect of TAK-044 on the arterial baroreflex function indicated by the slope of RSNA to the changes in MAP during phenylephrine and nitroprusside injection in both groups. Compared with the sham group, the HF group showed impaired arterial baroreflex control of RSNA during phenylephrine injection, and intravenous administration of TAK-044 normalized this abnormality, whereas the function in the sham group was not changed. These data show that ET AB antagonist suppressed renal sympathetic activity in rats with HF, and improved arterial baroreflex function. The beneficial effect of endothelin antagonist on heart failure may involve improvement of the increased sympathoexcitation and impaired arterial baroreflex function in HF. (Circ J 2002; 66: 841 - 845)