COMPARISON OF THE NITRIC-OXIDE AND CYCLOOXYGENASE PATHWAY IN MESENTERIC RESISTANCE VESSELS OF NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

1 The double perfused mesentery was used to compare arterial and venou s 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-n itro-L-arginine (L-NOARG) and N-G-nitro-L-arginine methyl ester (L-NAM E)) and cyclo-oxygenase (indomethacin, mefenamic acid). 2 KCl (20 to 1 20 mM K+) caused concentration-dependent increases in arterial and ven ous perfusion pressures. The maximal arterial effects were significant ly higher in the SHRs than in the WKY, with no differences in the veno us presser responses. 3 L-NAME and L-NOARG (100 mu M) 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 perf usion pressures in the venous mesenteric vessels isolated from WKY. 4 L-NAME and L-NOARG (100 mu M) potentiated the presser responses to KCl to the same extent in the venous and arterial beds derived from WKY;I nd SHR. while indomethacin and mefenamic acid (5 mu M) only significan tly decreased these responses in WKY. 5 Acetylcholine (ACh)-induced re laxations (1 nM to 10 mu M) were significantly higher in arterial beds of WKY than in SHR, without differences in the venous relaxant respon ses. 6 L-NAME (100 mu M) 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 p erfused mesenteric vasculatures requires an active tone and no dysfunc tion of NO synthase activity is functionally apparent in the mesenteri es isolated from SHRs. The cyclo-oxygenase pathway is only implicated in the KCl-induced responses of tissues derived from WKY, but not in t he vasodilatations induced by ACh in either the arterial or the venous vasculatures from WKY and SHR.