The Effect of Cromakalim on the Hindlimb Vascular Bed of the Male Rat: Do Glybenclamide and/or Nitric Oxide Modulate the Vasodilation?
Cromakalim, a benzopyran derivative, is a member of a novel class of antihypertensive agents that increase membrane K(+) conductance through ATP-sensitive K(+) channels. The effects of glybenclamide and N(omega)-L-arginine methyl ester (L-NAME), a specific inhibitor of nitric oxide synthesis from L-arginine were investigated on the vasodilator response to cromakalim in the hindlimb vascular bed in the male rat, as well as the combination glybenclamide and L-NAME. Thirty male Sprague--Dawley rats (350--450 g) were studied. Cromakalim in three doses (10, 30, 100 &mgr;g) injected into the hindlimb through a catheter induced a significant dose-dependent decrease in both mean arterial pressure (MAP) and hindlimb perfusion pressure (HPP). These responses were significantly modified by either glybenclamide or L-NAME. The role of a combination of glybenclamide and L-NAME on the vasodilator responses to cromakalim, acetylcholine, and nitroglycerin were also investigated. Three doses of either acetylcholine, nitroglycerin, or cromakalim caused dose-dependent reduction in HPP of the rats. The responses to acetylcholine were significantly blocked by L-NAME, but the responses to nitroglycerin were not. The vasodilation induced by cromakalim was not only partly blocked by glybenclamide but also by L-NAME. This blockade was significantly augmented when both glybenclamide and L-NAME were infused. These results suggest that nitric oxide may play an important role in regulating hindlimb vascular tone under physiologic conditions. The data also suggest that nitric oxide may be an additional mediator for cromakalim vasodilation as well as K(APT)(+) channel activation in the hindlimb vascular bed of the male rat.
Jahr
Jonathan S.
JS
Department of Anesthesiology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Feng
Chang Jian
CJ
Wang
Junke
J
Holton
Ronald
R
Cheng
David Y.
DY