Impairment of endothelium—dependent vasorelaxation in chronic two-kidney, one clip hypertensive rats

The present study was to investigate a role for endothelium-derived nitric oxide (EDNO) system in the development and maintenance of 2-kidney, 1 clip (2K1C) hypertension. Effects of blocking the synthesis or supplementing the precursor of EDNO on the developmental phase of hypertension were examined in 2K1C rats. Responses of the isolated vasculature to phenylephrine, acetylcholine, sodium nitroprusside, and atrial natriuretic peptide were also examined in chronic 2K1C rats. Ingestion of N G -nitro-L-arginine methyl ester or L-arginine did not affect the development of hypertension in 2K1C rats. Contraction response to phenylephrine was enhanced and relaxation response to acetylcholine was attenuated in the thoracic aortic ring isolated from chronic hypertensive rats, both being more marked in the 12-week hypertensive than in the 7-week hypertensive. Indomethacin did not significantly affect the degree of the attenuated vasorelaxation response to acetylcholine. The vasorelaxation response to sodium nitroprusside and atrial natriuretic peptide remained unaltered in the hypertensives. These results indicate that EDNO does not affect the developmental phase of 2KlC hypertension, whereas an impaired endothelium-dependent vasorelaxation is associated with chronic 2K1C hypertension.