IMPAIRMENT OF ENDOTHELIUM-DEPENDENT VASORELAXATION IN CHRONIC 2-KIDNEY, ONE-CLIP HYPERTENSIVE RATS

The present study was to investigate a role for endothelium-derived ni tric oxide (EDNO) system in the development and maintenance of 2-kidne y, 1 clip (2K1C) hypertension. Effects of blocking the synthesis or su pplementing the precursor of EDNO on the developmental phase of hypert ension were examined in 2K1C rats. Responses of the isolated vasculatu re to phenylephrine, acetylcholine, sodium nitroprusside, and atrial n atriuretic 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 phen ylephrine was enhanced and relaxation response to acetylcholine was at tenuated in the thoracic aortic ring isolated from chronic hypertensiv e rats, both being more marked in the 12-week hypertensive than in the 7-week hypertensive. Indomethacin did not significantly affect the de gree of the attenuated vasorelaxation response to acetylcholine. The v asorelaxation response to sodium nitroprusside and atrial natriuretic peptide remained unaltered in the hypertensives. These results indicat e that EDNO does not affect the developmental phase of 2K1C hypertensi on, whereas an impaired endothelium-dependent vasorelaxation is associ ated with chronic 2K1C hypertension.