Decreased Flow-Induced Dilation and Increased Production of cGMP in Spontaneously Hypertensive Rats

Abstract

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 mol/L) or sodium nitroprusside (0.1 mmol/L). Flow-induced release of cGMP was significantly greater in SHR than in WKY (PϽ0.01), despite a lower flow-induced dilation in SHR. In both strains, N G -nitro-L-arginine methyl ester (L-NAME) completely inhibited cGMP release in response to flow (PϽ0.001), 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 (82Ϯ3.5 fmol/min) than in WKY (66Ϯ3.5 fmol/min; PϽ0.05) and was associated with increased expression of endothelial NOS mRNA in SHR. Sodium nitroprusside induced larger increases in cGMP release in SHR (3593Ϯ304 fmol/min) than in WKY (2467Ϯ302 fmol/min; PϽ0.05). The release of cGMP in response to acetylcholine was significantly lower in SHR (292Ϯ80 fmol/min) than in WKY (798Ϯ218 fmol/min; PϽ0.05) 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. (Hypertension. 1998;32:1098-1103.)

Acetylcholine and bradykinin enhance hypotension and affect the function of remodeled conduit arteries in SHR and SHR treated with nitric oxide donors

“…In the present study, the enhanced extent of hypotension in SHR did not change after administration of molsidomine or PETN. The present findings are similar to those obtained in NO-deficient hypertension (6,8) although the etiopathogenic background, NO production, NO level, and cGMP level are different in these two experimental models of hypertension (29).…”

Role of SHP-1, Kv.1.2, and cGMP in nitric oxide-induced ERK1/2 MAP kinase dephosphorylation in rat vascular smooth muscle cells

“…For example, it is well known that flow-induced dilation involves nitric oxide release from endothelial cells, which is significantly altered in different arterial beds in hypertensive rats [27,28]. However, Qiu et al have shown a significant decrease in flow-induced dilation and at the same time an increase in cGMP production from endothelial mesenteric arteries in spontaneously hypertensive rats [29]. Our data may suggest that the response to nitric oxide, in addition its production, could be altered in hypertension thereby affecting the level of ERK1/2 MAP-kinase phosphorylation.…”

Fatty acid–induced changes in vascular reactivity in healthy adult rats

“…Indeed, SNP releases NO after intracellular metabolism in the vascular smooth muscle cells (VSMCs), leading to relaxation via a cyclic guanosine monophosphate-dependent mechanism [21]. Fig.…”