Antagonism of acetylcholine and adenosine rat cremaster arteriolar vasodilation by combination of NO antagonists.

It has become evident that complete elimination of the vasodilator response to agonists that require the release of nitric oxide (NO) is necessary for certain studies of the microcirculation. The A2 and A3 arterioles of the rat cremaster muscle microcirculation were studied by video-microscopy. At control, arterioles at rest or constricted by arginine vasopressin (AVP) were dilated by intra-arterially injected acetylcholine (ACh), intra-arterially injected adenosine (ADO) and topical adenosine. The NO antagonists, Nw-nitro-L-arginine methyl ester (L-NAME) and hydroquinone (HQ), which acts as an antagonist by generating free radicals, in maximal doses, individually partially blocked the vasodilator actions of intra-arterial ACh and intra-arterial ADO. Combining L-NAME and HQ eliminated the vasodilation by intra-arterial ACh and intra-arterial ADO. Sodium nitroprusside dilated the arterioles to the resting level or above at control and in the presence of the antagonists either individually or when combined. However, the NO antagonists did not block the arteriolar vasodilator responses to topical ADO. The reduction of the production of NO and enhancement of its destruction by superoxide radicals results in the total absence of the vasodilator response due to intra-arterially injected acetylcholine and adenosine. The data suggest that luminal ADO receptors cause arteriolar dilation by endothelial-dependent mechanisms and abluminal receptors cause dilation by another mechanism.