Alteration of endothelial function in arterioles of renal hypertensive rats at two levels of vascular tone

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Design:Arterioles were studied in vivo to determine whether the altered response to endothelium-dependent and -independent vasodilators in one-kidney, one clip (1K1C) hypertensive rats was related to increased vascular tone or precontraction with norepinephrine.Methods:Acetylcholine, bradykinin and nitroprusside were applied topically to arterioles in the spinotrapezius muscle of 4-week 1K1C hypertensive rats and normotensive control rats. The changes in internal diameter of arcade arterioles in response to four doses of each drug were measured with intravital microscopy before and during superfusion of indomethacin. Arteriolar responses were redetermined during enhancement of vascular tone by superfusion of norepinephrine.Results:Vasodilation in response to acetylcholine, but not to nitroprusside, was reduced in 1K1C rats compared with normotensive rats. Indomethacin decreased the resting arteriolar diameter, but did not alter the response to acetylcholine or nitroprusside. The response to bradykinin, which was partly attenuated after cyclo-oxygenase inhibition, was also reduced in 1K1C rats. The attenuated endothelium-dependent responses in 1K1C rats may have been a result of changes in the synthesis or release of endothelium-derived relaxing factor because the response to the endothelium-independent vasodilator nitroprusside was unchanged. Indomethacin attenuated the vasodilation of bradykinin, which suggests that prostacyclin is involved in this action in vivo.Conclusions:Precontraction with norepinephrine did not change any of the responses, indicating that the reduced endothelial-dependent responses in hypertensive rats cannot be explained by differences in vascular tone.

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