Effect of indomethacin on the microvessel reactivity of two-kidney, one-clip hypertensive rats.

ABSTRACT

Endothelial cells modulate vascular tone by releasing endothelium-derived relaxing and contracting factors. An imbalance of these factors in hypertension could contribute to increased peripheral vascular resistance. To investigate whether an endothelium-derived contracting factor is involved in the altered reactivity of microvessels of two-kidney, one-clip hypertensive rats, mesenteric arterioles either perfused in vitro or studied in vivo were used. In two-kidney, one-clip hypertensive rats, a potentiation to noradrenaline was observed in preparations tested either in vitro or in vivo. Indomethacin treatment did not correct the increased response to noradrenaline in microvessel preparations. Thus the involvement of an endothelium-derived contracting factor which is sensitive to indomethacin blockade, could be discarded. A decreased response to acetylcholine, an endothelium-dependent vasodilator, was observed in in vitro and in vivo preparations. The responses to sodium nitroprusside, an endothelium-independent vasodilator, were not altered in microvessel preparations of hypertensive rats. In two-kidney, one-clip hypertensive preparations, indomethacin normalized the endothelium-dependent relaxations. Relaxations to sodium nitroprusside were not altered by indomethacin. It is suggested that endothelium-dependent relaxations are impaired in two-kidney, one-clip hypertension because of a cyclooxygenase-dependent substance interfering with the release and/or action of endothelium-dependent relaxing factor.