Mechanisms of Acetylcholine-Induced Vasorelaxation in High K+-Stimulated Rabbit Renal Arteries
Journal of Veterinary Medical Science
To characterize the mechanisms of acetylcholine (ACh)-induced vasorelaxation in rabbit renal arteries precontracted with high K + (100 mM), muscle tension and cytosolic free Ca 2+ concentration ([Ca 2+ ] i ) were measured simultaneously in the fura-2-loaded arterial strips. In the artery with endothelium, high K + increased both [Ca 2+ ] i and muscle tension. Addition of ACh (10 µM) during high-K + induced contraction significantly relaxed the muscle and induced additional increase in [Ca 2+ ]
... crease in [Ca 2+ ] i . In the presence of NG-nitro-L-arginine (L-NAME, 0.1 mM), ACh increased [Ca 2+ ] i without relaxing the muscle. In the artery without endothelium, high K + increased both [Ca 2+ ] i and muscle tension although ACh was ineffective, suggesting that ACh acts selectively on endothelium to increase [Ca 2+ ] i . 4-DAMP (10 nM) or atropine (0.1 µM) abolished the ACh-induced increase in [Ca 2+ ] i and relaxation. However, pirenzepine (0.1 µM), AF-DX 116 (1 µM) and tropicamide (1 µM) were ineffective. The ACh-induced increase of [Ca 2+ ] i and vasorelaxation was significantly reduced by 3 µM gadolinium, 10 µM lanthanum or 10 µM SKF 96365. These results suggest that, in rabbit renal artery, ACh-evoked relaxation of 100 mM K + -induced contractions is mediated by the release of endothelial NO. ACh may stimulates the M 3 subtype of muscarinic receptor in the endothelial cells, resulting in the opening of the nonselective cation channels followed by an increase of [Ca 2+ ] i and stimulation of NO synthase.