THE ROLE OF THROMBOXANE-A(2) IN THE ALTERED MICROVASCULAR REACTIVITY IN 2-KIDNEY, ONE-CLIP HYPERTENSION

To investigate the nature of the arachidonic acid metabolite involved in the altered reactivity of microvessels of two-kidney, one-clip hype rtensive rats and the possible contribution of this product to the ele vated blood pressure levels found in two-kidney, one-clip hypertension , mesenteric arterioles either perfused in vitro or studied in vivo we re used along with blood pressure determinations. The decreased respon se to acetylcholine observed was normalized by ridogrel, a thromboxane A(2) receptor antagonist, and dazoxiben, a thromboxane A(2) synthase inhibitor. The smooth muscle response to nitric oxide, tested with sod ium nitroprusside, was unaltered in two-kidney, one-clip hypertensive microvessels. Neither ridogrel nor dazoxiben modified the response to this vasodilator. In contrast, the potentiated response to noradrenali ne was corrected by ridogrel and dazoxiben in vitro but not in vivo. N oradrenaline and acetylcholine increased the release of thromboxane A( 2) from the mesenteric microvessels of two-kidney, one-clip hypertensi ve rats. Ridogrel and dazoxiben decreased but did not normalize the el evated blood pressure of hypertensive rats. Based on these results, we concluded that: 1) the decreased responsiveness of smooth muscle to a cetylcholine resulted from an increase in thromboxane A(2) formation r ather than a decrease in sensitivity to nitric oxide; 2) thromboxane A (2) contributes to the increased noradrenaline response in mesenteric microvessels perfused in vitro while in in vivo other blood borne vaso active agents may also be involved since the potentiated noradrenaline response was not corrected by inhibiting thromboxane A(2) synthesis o r receptors; 3) in addition to thromboxane A(2), another as yet uniden tified factor, may contribute to the elevated blood pressure in two-ki dney, one-clip hypertension.