Chronic Endothelin-1 Improves Nitric Oxide–Dependent Flow-Induced Dilation in Resistance Arteries From Normotensive and Hypertensive Rats

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Abstract
—Endothelin-1 (ET-1) is released on stimulation by shear stress of the vascular wall. In several pathological situations, an involvement of ET-1 is suspected. Nevertheless, the effect of a chronic increase in circulating ET-1 on vascular tone in resistance arteries is not yet fully understood. We investigated the response to tensile stress (pressure-induced myogenic tone) and shear stress (flow-induced dilation, FD) of rat mesenteric resistance arteries cannulated in an arteriograph. Intraluminal diameter was measured continuously. Rats (normotensive Wistar-Kyoto rats [WKYs] and spontaneously hypertensive rats [SHRs]) were treated for 2 weeks with ET-1 (5 pmol · kg−1· min−1SC; n=8 to 16 per group). Systolic arterial blood pressure increased significantly in ET-1–treated rats (171±7 versus 196±6 mm Hg in WKYs and 216±8 versus 245±6 mm Hg in SHRs,PPNG-nitro-l-arginine methyl ester (L-NAME; 100 μmol/L) attenuated FD in WKYs (eg, 22±2 versus 15±3 μm after L-NAME, flow=150 μL/min) and, to a lesser extent, in SHRs (P<0.001 versus WKYs). The cyclooxygenase inhibitor indomethacin (3 μmol/L) attenuated the remaining FD in WKYs (eg, 15±3 versus 8±3 μm, flow=150 μL/min) and in SHRs (eg, 7.5±0.5 versus 5.0±0.6 μm). Chronic ET-1 significantly increased FD in SHRs but not in WKYs. In both strains, NO-dependent FD was significantly increased by chronic ET-1. Furthermore, indomethacin-sensitive FD was increased by chronic ET-1 in SHRs only. Thus, chronic ET-1 increased NO-dependent FD in resistance mesenteric arteries from both WKYs and SHRs and increased indomethacin-sensitive FD in SHRs only.