ANGIOTENSIN-II INCREASES TISSUE ENDOTHELIN AND INDUCES VASCULAR HYPERTROPHY - REVERSAL BY ETA-RECEPTOR ANTAGONIST

Background In vitro studies on vascular smooth muscle cells suggest th at endothelin has a stimulating effect on cellular proliferation. This study was designed to determine the endogenous effect of endothelin o n angiotensin II-induced hypertrophy of small arteries in vivo. Method s and Results Two weeks of angiotensin II administration (200 ng.kg(-1 ).min(-1)) increased media thickness, media/lumen ratio, and cross-sec tional area of basilar and small mesenteric arteries, confirming the p roliferative properties of angiotensin II. The tissue levels of endoth elin-l were elevated in mesenteric arteries after angiotensin II admin istration. The administration of the selective and specific ETA-recept or antagonist LU135252 (50 mg.kg(-1).d(-1)) in combination with angiot ensin II prevented the changes of vascular geometry and partially redu ced the increase in blood pressure induced by angiotensin II. Indeed, part of the effect on the vascular structure of the endothelin-recepto r antagonist seemed pressure-independent. Conclusions Our results ther efore demonstrate that angiotensin II increases the production of endo thelin in the blood vessel wall that, via ETA receptors, mediates chan ges in vascular structure of the cerebral and mesenteric circulation. Endothelin antagonists may therefore be of value to reduce blood press ure and to prevent vascular structural changes in conditions of increa sed activity of the renin-angiotensin system.