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In smooth muscle, contractions under pharmacomechanical and electromechanical coupling mechanism control rely on mobilization of intracellular calcium and on calcium influx from the extracellular space, respectively. In airway smooth muscle, pharmacomechanical coupling seems to predominate. Even if extracellular calcium enters the cell during agonist stimulation, and contributes to the maintained plateau phase of a prolonged stimulation-induced contraction, it does not result from membrane depolarization and is not part of the electromechanical coupling mechanism. Pharmacomechanical and electromechanical coupling are most likely not independent processes: we present here an example of cross talk between plasma membrane and sarcoplasmic reticulum, which results in an almost complete switch in the E-C coupling process from pharmaco- to electromechanical mode in tracheal smooth muscle.

Using a recognized inhibitor of nitric oxide (NO) synthesis, Nw-nitro L-arginine methyl ester (L-NAME), we tested the hypothesis of the existence of a nonendothelial source of NO in vascular tissue using rings of rat thoracic aorta in which endothelial cells have been removed by mechanical abrasion and have totally lost their endothelium-dependent relaxation. Contractility of the muscle was tested by recording the concentration-dependent contraction of the preparations induced by an alpha-adrenergic agonist, phenylephrine. Contractility in aortas from Wistar-Kyoto normotensive rats (WKY) and spontaneous hypertensive rats (SHR) was not significantly affected by a 30-min to 2-hour incubation with L-NAME prior to agonist stimulation. However, preparations incubated for 30 min with 1 mM L-arginine (L-ARG) and then washed for 1 h in standard Krebs solution had a significantly reduced contraction to phenylephrine in both WKY and SHR. In these preparations pretreated with L-ARG, L-NAME significantly increased contractility in both WKY and SHR; this effect was prevented by L-ARG but not by D-arginine. Responses to phenylephrine were not inhibited by L-ARG when preparations were incubated from the beginning of the experiment with 1 mM cycloheximide, thus suggesting a dependence on protein synthesis of the attenuation of contraction seen with L-ARG. Intact aortic rings processed for NADPH diaphorase histochemistry, a putative marker for NO synthase, showed NADPH diaphorase reactivity only in the endothelial layer and in the adventitia.(ABSTRACT TRUNCATED AT 250 WORDS)