Endothelium-dependent relaxation and L-arginine metabolism in genetic hypertension

This study characterizes the effects of L-arginine and N(G)-monomethyl L- arginine on dilator responsiveness of vascular tissue from Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats. Rings of abdominal aorta were suspended in tissue baths for measurement of isometric force. After contraction induced by phenylephrine, cumulative addition of acetylcholine, L-arginine, or A23187 to the muscle bath caused a similar relaxation of aortic rings in both animal groups. To test the hypothesis that arginine metabolism is altered in hypertension, aortic rings were incubated with N(G)- monomethyl L-arginine. N(G)-monomethyl L-arginine (10-300 μM) did not affect contractile responses to phenylephrine (10^-10 to 10^-4 M) in either animal group (EC₅₀, 10^-7 M). Exposure of aortic rings to N(G)-monomethyl L-arginine resulted in a greater inhibition of relaxation response to acetylcholine (10^-10 to 10^-6 M) in hypertensive animals. N(G)-monomethyl L-arginine (300 μM) caused complete inhibition of relaxation to acetylcholine in the hypertension group. Incubation with L-arginine (10-100 μM) overcame the inhibition of acetylcholine-induced relaxation produced by N(G)-monomethyl L-arginine in both groups. Exposure of aortic ring segments to N(G)-monomethyl L-arginine attenuated relaxation responses to A23187 (10^{- 10} to 3 x 10^-6 M) in both groups. L-Arginine-induced reversal of the inhibitory effect of N(G)-monomethyl L-arginine on the relaxation responses to A23187 was similar between groups. We conclude that the inhibitory effect of N(G)-monomethyl L-arginine on endothelium-derived relaxing factor production in response to acetylcholine is greater in stroke-prone spontaneously hypertensive rats as compared with Wistar-Kyoto rats. This finding reflects differences in L-arginine metabolism in genetic hypertension that may be an important factor in contributing to altered vascular reactivity.