Suppression of acetylcholine-induced relaxation by local anesthetics and vascular NO-cyclic GMP system

Background: Local anesthetics have been demonstrated to attenuate acetylcholine-induced relaxation of vascular smooth muscle, but the mechanism responsible has not been elucidated. The present study was undertaken to ascertain whether this effect of local anesthetics is due to suppression of the vascular nitric oxide (NO)-cyclic GMP (cGMP) system. Methods: Isolated rat aortae were cut into helical strips and mounted in bathing solution to measure isometric tension changes. They were precontracted with phenylephrine (0.3 μM)then exposed to cumulative concentrations of relaxants including acetylcholine, sodium nitroprusside (SNP) and papaverine, in the absence or presence of local anesthetics. Aortaefor cGMP measurements were cut longitudinally into pairs of strips and bathed in the solution without tension. In the absence or presence of anesthetics, they were stimulated with acetylcholine or SNP, and the cGMP content of each strip was radioimmunoassayed. Results: Acetylcholine-induced, endothelium-dependent relaxation of phenylephrine-precontracted aortae was attenuated by lidocaine (30–300 μM), tetracaine (10–30 μM), bupivacaine (10–100 μM) and ropivacaine (30–100 μM). SNP-inducedrelaxation was attenuated by lidocaine (300 μM), tetracaine (30 μM), bupivacaine (10–100 μM) and ropivacaine (30–100 μM). Papaver-ine-induced relaxation was attenuated by lidocaine (300 μM), bupivacaine (30–100 μM) and ropivacaine(30–100 μM), and augmented by tetracaine (30 μM). Cyclic GMP levels in acetylcho-line-stimulated aortae were reduced significantly by lidocaine (300 μM), tetracaine(100 μM) and bupivacaine (300 μM) treatment, but not by ropivacaine (300 μM). SNP-stimulated cGMP levels were reduced by tetracaine (100 μM) but not by any other anesthetics at the concentrations tested. Conclusion: We conclude that lidocaine, tetracaine and bupivacaine suppress acetylcholme-stimulated formation of cGMP. However, the attenuation of acetylcholine-induced relaxation by local anesthetics is not totally ascribable to reduced cGMP levels.