Analysis of l-NAME-dependent and -resistant responses to acetylcholine in the rat

The mechanism by which acetylcholine (ACh) decreases systemic arterial pressure and hindlimb vascular resistance was investigated in the anesthetized rat. ACh injections caused dose-dependent decreases in systemic arterial pressure and hindlimb vascular resistance. Nω-nitro-l-arginine methyl ester (l-NAME) had little effect on the magnitude of depressor and vasodilator responses but decreased response duration when baseline parameters were corrected by a nitric oxide (NO) donor infusion. The decrease in the duration of the ACh depressor response was prevented by the administration of excess l-arginine. The l-NAME-resistant component of the depressor response to ACh was attenuated by ebselen, a glutathione peroxidase mimic. The calcium-activated potassium (KCa) antagonists charybdotoxin (ChTX) and apamin decreased the magnitude but not the duration of the hindlimb vasodilator response to ACh. The combination of l-NAME, ChTX, and apamin reduced the magnitude and duration of the vasodilator response to ACh b...