Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2148-2153
© 1999 American Heart Association, Inc.
Vascular Biology |
Chronic Endothelin-1 Improves Nitric Oxide–Dependent Flow-Induced Dilation in Resistance Arteries From Normotensive and Hypertensive Rats
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-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 µm in WKYs and from 62±6 to 149±7 µm in SHRs (pressure from 10 to 150 mm Hg). Myogenic tone was not significantly affected by chronic ET-1. Flow (9 to 150 µL/min) significantly increased the arterial diameter by 2±0.5 to 22±2 µm in WKYs and by 1.3±0.7 to 8.3±0.8 µm in SHRs (P<0.001 versus WKYs). The NO synthesis blocker NG-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.
Key Words: myogenic tone • shear stress • resistance arteries • endothelin • hypertension
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