Reduction of contractions to phenylephrine by L-NAME in the carotid artery of mice with endothelial overexpression of endothelin-1

Abstract

The release of endothelium-derived contracting factors (EDCF) is increased by exogenous endothelin-1 (ET-1). Experiments were designed to determine whether or not endothelial overexpression of ET-1 affects vascular responsiveness. Carotid artery rings with endothelium of control mice and mice with endothelial overexpression of ET-1 (TET-1) were contracted with the α1-adrenoceptor agonist phenylephrine in the absence or presence of the eNOS inhibitor L-NAME and exposed to acetylcholine. After washout, the rings were contracted with increasing concentrations of the TP receptor agonist U46619. EDCF-mediated increases in tension caused by acetylcholine were augmented in TET-1 arteries compared to controls both in the absence and presence of LNAME. In the presence of the latter, TET-1 rings showed stronger contractions to U46619 than controls. By contrast, contractions to phenylephrine were reduced by L-NAME in TET-1 arteries with a rightward shift and loss of the sigmoidal shape of the concentration-response curve. These results imply a role of endothelial ET-1 in EDCF-mediated contractions and indicate an increased TXA2 receptor signaling in vascular smooth muscle cells. They do not provide an explanation for the decreased response to α1-adrenergic activation in TET-1 arteries in the absence of NO.