A non-cyclo-oxygenase, non-nitric oxide relaxing factor is present in resistance arteries of normotensive but not spontaneously hypertensive rats.

The present experiments tested the hypothesis that decreased production of an endothelium-derived relaxing factor in arteries of hypertensive animals contributes to impaired endothelium-dependent relaxation. Acetylcholine-induced relaxation of freshly isolated spontaneously hypertensive rat (SHR) vessels pre-contracted with norepinephrine was impaired compared with Wistar-Kyoto rats (WKY). 10 microM indomethacin partially normalized the SHR response. Inhibition of nitric oxide synthesis with 100 microM nitro-L-arginine methyl ester or 100 microM NG-monomethyl arginine shifted the acetylcholine relaxation curve to the right, but had no effect on the maximal relaxation in WKY and completely inhibited relaxation of SHR. A similar pattern was observed with methylene blue (0.3 microM). Acetylcholine-induced relaxation of WKY vessels pre-contracted with 5 microM norepinephrine and 100 mM K+ was attenuated 60% compared with vessels pre-contracted with norepinephrine alone, and was completely inhibited by nitro-L-arginine methyl ester; relaxation of SHR vessels was decreased by 50%. Six-hour storage at 37 degrees C significantly attenuated acetylcholine-induced relaxation in both strains; treatment with indomethacin improved the response. Moreover, relaxation of WKY vessels was completely inhibited by nitro-L-arginine methyl ester and NG-monomethyl arginine after the storage period. The absence of L-arginine-induced relaxation and lack of effect of supplementation with L-arginine indicated that the constitutively active NO synthetase was not induced and that L-arginine substrate was limiting. The results indicate that mesenteric resistance arteries of the WKY express a relaxing factor generated by a non-cyclo-oxygenase, non-nitric oxide synthetase pathway that is possibly a hyperpolarizing factor.(ABSTRACT TRUNCATED AT 250 WORDS)