Mechanisms of Acetylcholine-Induced Vasorelaxation in High K⁺-Stimulated Rabbit Renal Arteries

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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 ([Ca²⁺]_i) were measured simultaneously in the fura-2-loaded arterial strips. In the artery with endothelium, high K⁺ increased both [Ca²⁺]_i and muscle tension. Addition of ACh (10 μM) during high-K⁺ induced contraction significantly relaxed the muscle and induced additional increase in [Ca²⁺]_i. In the presence of NG-nitro-L-arginine (L-NAME, 0.1 mM), ACh increased [Ca²⁺]_i without relaxing the muscle. In the artery without endothelium, high K⁺ increased both [Ca²⁺]_i and muscle tension although ACh was ineffective, suggesting that ACh acts selectively on endothelium to increase [Ca²⁺]_i. 4-DAMP (10 nM) or atropine (0.1 μM) abolished the ACh-induced increase in [Ca²⁺]_i and relaxation. However, pirenzepine (0.1 μM), AF-DX 116 (1 μM) and tropicamide (1 μM) were ineffective. The ACh-induced increase of [Ca²⁺]_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 M₃ subtype of muscarinic receptor in the endothelial cells, resulting in the opening of the nonselective cation channels followed by an increase of [Ca²⁺]_i and stimulation of NO synthase.