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

L. Lee, R. C. Webb

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)435-441
Number of pages7
JournalHypertension
Volume19
Issue number5
DOIs
StatePublished - Jan 1 1992

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Keywords

  • arginine
  • endothelium
  • genetic hypertension
  • rat studies

ASJC Scopus subject areas

  • Internal Medicine

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