Chronic endothelin-1 improves nitric oxide-dependent flow-induced dilation in resistance arteries from normotensive and hypertensive rats.
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.
Henrion
D
D
Institut National de la Santé et de la Recherche Médicale (INSERM) U 141, Paris, France. daniel.henrion@inserm.lrb.ap-hop-paris.fr
Iglarz
M
M
Lévy
B I
BI
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019332:Endothelin-1 / Q000008:administration & dosage* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011312:Pressure; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012016:Reference Values; D012039:Regional Blood Flow / Q000502:physiology; D013314:Stress, Mechanical; D013997:Time Factors; D014655:Vascular Resistance; D014664:Vasodilation / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin