Impairement of endothelium-dependent relaxation in chronic two-kidney, one clip hypertensive rats.

OBJECTIVES

Hypertension is commonly associated with an endothelial dysfunction that may contribute to the rise in blood pressure. Little information has been available so far on the role of endothelium-derived nitric oxide(EDNO) in renin-dependent, 2-kidney, 1 clip(2KIC) hypertension. The present study was aimed to determine a role for EDNO in the development and maintenance of 2KIC hypertension.

METHODS

The effects of blocking synthesis or supplementation with precursor of EDNO on the development of hypertension were determined in 2KIC rats. Vascular responses to acetylcholine, nitroprusside, atrial natriuretic peptide and nifedipine were examined in 7- and 12-week hypertensive 2KIC rats.

RESULTS

NG-nitro-L-arginine-methyl ester caused a sustained increase of blood pressure in normal rats, while it was only partially associated with a more pronounced increase of blood pressure in the developmental phase of hypertension in 2KIC rats. In 7-week and 12-week hypertensive rats, phenylephrine-induced contraction of the isolated thoracic aortic rings was more sensitive compared with control. Their acetylcholine-induced relaxation was attenuated while the responses to nitroprusside or atrial natriuretic peptide were unaltered. Although their blood pressure did not differ between 7-week and 12-week hypertensive groups, the attenuation in the acetylcholine-induced relaxation was more prominent in the latter with a longer duration of hypertension. Indomethacin did not affect the attenuated relaxation to acetylcholine. The relaxation response to nifedipine was more pronounced in 2KIC rats.

CONCLUSION

These results indicate that ENDO has little influence of the 2KIC hypertension, at least during its developmental phase, which is associated with an activated reninangiotensin system. The chronic stage of 2KIC hypertension, however, is associated with an endothelial dysfunction which may contribute to the enhanced vasoconstriction and sustained high blood pressure.