(Hypertension. 1998;32:1098-1103.)
© 1998 American Heart Association, Inc.
Scientific Contributions |
Decreased Flow-Induced Dilation and Increased Production of cGMP in Spontaneously Hypertensive Rats
From the Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 141 and Unit 127 (C.H.), IFR Circulation-Lariboisière, Université Paris VII, Hôpital Lariboisière, Paris, France.
Correspondence to Dr Bernard Levy, INSERM U 141, 41 Blvd de la Chapelle, Hôpital Lariboisière 75475 Paris cedex 10, France. E-mail levy{at}infobiogen.fr
Abstract—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 µmol/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.
Key Words: endothelium • cyclic GMP • nitric oxide synthase • mesenteric arteries
This article has been cited by other articles:
 |
|
 |
|
  X. Zhou, H. G. Bohlen, S. J. Miller, and J. L. Unthank NAD(P)H oxidase-derived peroxide mediates elevated basal and impaired flow-induced NO production in SHR mesenteric arteries in vivo Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1008 - H1016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. I. Palen, S. Belmadani, P. A. Lucchesi, and K. Matrougui Role of SHP-1, Kv.1.2, and cGMP in nitric oxide-induced ERK1/2 MAP kinase dephosphorylation in rat vascular smooth muscle cells Cardiovasc Res, November 1, 2005; 68(2): 268 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Hassoun, G. Filippov, M. Fogel, C. Donaldson, U. S. Kayyali, L. A. Shimoda, and K. D. Bloch Hypoxia Decreases Expression of Soluble Guanylate Cyclase in Cultured Rat Pulmonary Artery Smooth Muscle Cells Am. J. Respir. Cell Mol. Biol., June 1, 2004; 30(6): 908 - 913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Iaccarino, M. Ciccarelli, D. Sorriento, E. Cipolletta, V. Cerullo, G. L. Iovino, A. Paudice, A. Elia, G. Santulli, A. Campanile, et al. AKT Participates in Endothelial Dysfunction in Hypertension Circulation, June 1, 2004; 109(21): 2587 - 2593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. KOHLER, R. KREUTZ, A. GRUNDIG, L. ROTHERMUND, C. YAGIL, Y. YAGIL, A. R. PRIES, and J. HOYER Impaired Function of Endothelial Pressure-Activated Cation Channel in Salt-Sensitive Genetic Hypertension J. Am. Soc. Nephrol., August 1, 2001; 12(8): 1624 - 1629. [Abstract] [Full Text] [PDF]
|
|