Decreased flow-induced dilation and increased production of cGMP in spontaneously hypertensive rats.
-We investigated flow (shear stress)- and agonist-induced cGMP release in mesenteric vascular beds of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). The mesenteric vascular bed was perfused in situ with Tyrode's solution. Vascular relaxation and cGMP release in the perfusate were determined on stimulation by flow or by acetylcholine (0.1 micromol/L) or sodium nitroprusside (0.1 mmol/L). Flow-induced release of cGMP was significantly greater in SHR than in WKY (P<0.01), despite a lower flow-induced dilation in SHR. In both strains, NG-nitro-L-arginine methyl ester (L-NAME) completely inhibited cGMP release in response to flow (P<0.001), although flow-induced dilation was not affected by L-NAME in SHR. Moreover, the activity of the constitutive nitric oxide synthase (NOS) was significantly greater in SHR (82+/-3.5 fmol/min) than in WKY (66+/-3.5 fmol/min; P<0.05) and was associated with increased expression of endothelial NOS mRNA in SHR. Sodium nitroprusside induced larger increases in cGMP release in SHR (3593+/-304 fmol/min) than in WKY (2467+/-302 fmol/min; P<0.05). The release of cGMP in response to acetylcholine was significantly lower in SHR (292+/-80 fmol/min) than in WKY (798+/-218 fmol/min; P<0.05) in parallel with smaller acetylcholine-induced relaxation in SHR. Despite increased cGMP production in response to flow and NOS activity, flow-induced dilation was decreased in SHR, suggesting an upregulation of the NO/cGMP pathway to compensate for the increased vascular tone in SHR.
Qiu
H Y
HY
Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 141, IFR Circulation-Lariboisière, Université Paris VII, Hôpital Lariboisière, Paris, France.
Henrion
D
D
Benessiano
J
J
Heymes
C
C
Tournier
B
B
Levy
B I
BI
D000109:Acetylcholine; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008638:Mesenteric Arteries / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D010477:Perfusion; D010641:Phenotype; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation
D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D000109:Acetylcholine