Comparison of the nitric oxide and cyclo-oxygenase pathway in mesenteric resistance vessels of normotensive and spontaneously hypertensive rats

Abstract

1. The double perfused mesentery was used to compare arterial and venous KCl- and acetylcholine (ACh)-induced responses in tissues taken from normotensive (WKY) and spontaneously hypertensive rats (SHR), in the presence or absence of inhibitors of nitric oxide (NO) synthase (N(G)-nitro-L-arginine (L-NOARG) and N(G)-nitro-L-arginine methyl ester (L-NAME)) and cyclo-oxygenase (indomethacin, mefenamic acid). 2. KCl (20 to 120 mM K+) caused concentration-dependent increases in arterial and venous perfusion pressures. The maximal arterial effects were significantly higher in the SHRs than in the WKY, with no differences in the venous presser responses. 3. L-NAME and L-NOARG (100 μM) had no effect on the basal perfusion pressures in tissues from either WKY or SHRs, and mefenamic acid only induced a significant reduction of the basal perfusion pressures in the venous mesenteric vessels isolated from WKY. 4. L-NAME and L-NOARG (100 μM) potentiated the presser responses to KCl to the same extent in the venous and arterial beds derived from WKY and SHR, while indomethacin and mefenamic acid (5 μM) only significantly decreased these responses in WKY. 5. Acetylcholine (ACh)-induced relaxations (1 nM to 10 μM) were significantly higher in arterial beds of WKY than in SHR, without differences in the venous relaxant responses. 6. L-NAME (100 μM) inhibited ACh-induced relaxations in arterial and venous beds from both groups of rats. Mefenamic acid was without effect on ACh-induced relaxations in either the arterial or the venous beds from WKY and SHR. 7. In conclusion, the liberation of NO in the perfused mesenteric vasculatures requires an active tone and no dysfunction of NO synthase activity is functionally apparent in the mesenteries isolated from SHRs. The cyclo-oxygenase pathway is only implicated in the KCl-induced responses of tissues derived from WKY, but not in the vasodilatations induced by ACh in either the arterial or the venous vasculatures from WKY and SHR.