Chronic endothelin-1 improves nitric oxide-dependent flow-induced dilation in resistance arteries from normotensive...

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(-1) SC; 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, P<0.05). Passive arterial diameter in isolated resistance arteries ranged from 78+/-9 to 169+/-4 microm in WKYs and from 62+/-6 to 149+/-7 microm in SHRs (pressure from 10 to 150 mm Hg). Myogenic tone was not significantly affected by chronic ET-1. Flow (9 to 150 microL/min) significantly increased the arterial diameter by 2+/-0.5 to 22+/-2 microm in WKYs and by 1.3+/-0. 7 to 8.3+/-0.8 microm in SHRs (P<0.001 versus WKYs). The NO synthesis blocker N(G)-nitro-L-arginine methyl ester (L-NAME; 100 micromol/L) attenuated FD in WKYs (eg, 22+/-2 versus 15+/-3 microm after L-NAME, flow=150 microL/min) and, to a lesser extent, in SHRs (P<0.001 versus WKYs). The cyclooxygenase inhibitor indomethacin (3 micromol/L) attenuated the remaining FD in WKYs (eg, 15+/-3 versus 8+/-3 microm, flow=150 microL/min) and in SHRs (eg, 7.5+/-0.5 versus 5.0+/-0.6 microm). 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.