Chronic endothelin-1 improves nitric oxide-dependent flow-induced dilationin resistance arteries from normotensive and hypertensive rats

Endothelin- 1 (ET-1) is released on stimulation by shear stress of the vasc ular wall. In several pathological situations, an involvement of ET-I is su spected. Nevertheless, the effect of a chronic increase in circulating ET-I on vascular tone in resistance arteries is not yet fully understood. We in vestigated the response to tensile stress (pressure-induced myogenic tone) and shear stress(flow-induced dilation FD)of rat mesenteric; resistance art eries;pe pressure -induced myogenic tone and shear stress flow -induced dil ation FD of rat mesenteric resistance arteries cannulated in an arteriograp h. Intraluminal diameter was measured continuously. Rats (normotensive Wist ar-Kyoto rats [WKYs] and spontaneously hypertensive rats SHRs) were treated for 2 weeks with ET-I (5 pmol kg(-1) min(-1)] SC; n=8 to 16 per group). Sy stolic arterial blood pressure increased significantly in ET-l-treated rats (171 +/- 7 versus 196 +/- 6 mm Hg in WKYs and 216 +/- 8 versus 245 +/- 6 m m Hg in SHRs, P<0.,05). Passive arterial diameter in isolated resistance ar teries ranged from 78 +/- 9 to 169 +/- 4 mu m in WKYs and from 62 +/- 6 to 149 +/- 7 mu m in SHRs (pressure from 10 to 150 mm Hg). Myogenic tone was n ot significantly affected by chronic ET-1. Flow (9 to 150 mu L/min) signifi cantly increased the arterial diameter by 2 +/- 0.5 to 22 +/- 2 mu m in WKY s and by 1.3 +/- 0.,7 to 8.3 +/- 0.8 mu m in SHRs (P<0.001 versus WKYs). Th e NO synthesis blocker NG-nitro-L-arginine methyl ester (L-NAME; 100 mu mol /L attenuated FD in WKYs (eg, 22 +/- 2 versus 15 +/- 3 mu m after L-NAME, f low=150 mu L/min) and, to a lesser extent, in SHRs (P<0.001 versus WKYs). T he cyclooxygenase inhibitor indomethacin (3 mu mol/L) attenuated the remain ing FD in WKYs leg, 15 +/- 3 versus 8 +/- 3 mu m, flow= 150 mu L/min) and i n SHRs leg, 7.5 +/- 0.5 versus 5.0 +/- 0.6 mu m). Chronic ET-1 significantl y increased FD in SHRs but not in WKYs. In both strains, NO-dependent FD wa s significantly increased eased by chronic ET-I. Furthermore, indomethacin- sensitive FD was increased by chronic ET-I in SHRs only. Thus, chronic ET-I increased NO-dependent FD in resistance mesenteric arteries from both WKYs and SHRs and increased indomethacin-sensitive FD in SHRs only. (Arterioscl er Thr omb Vase Biol. 1999;19:2148-2153,)