Signal transduction in spontaneous myogenic tone in isolated arterioles from rat skeletal muscle

Objective: The mechanism of spontaneous myogenic tone was investigated in i solated arteriolar segments. Methods: Arterioles were isolated from rat cre master muscle. Segments were endothelium-denuded and mounted in a pressure myograph at 75 mmHg. Under this condition, segments spontaneously constrict ed from a passive diameter of 167+/-3 to 82+/-4 mu m (n=41). The effects of several inhibitors were tested on the maintenance of myogenic tone. Result s: Gadolinium (10(-6)-10(-4) M), a putative inhibitor of stretch-activated cation channels, was ineffective. The phospholipase C (PLC) inhibitor 2-nit ro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC) induced a dose-dependent in hibition of tone. NCDC inhibited phenylephrine- (10(-6) M), but not potassi um buffer-induced (100 mM) constriction. The protein kinase C (PKC) inhibit ors staurosporine, chelerythrine and calphostin C inhibited myogenic tone i n a concentration-dependent manner. At an intermediate concentration, calph ostin C selectively inhibited phenylephrine-induced constriction. However, all PKC inhibitors abolished responses to phenylephrine and potassium buffe r at higher concentrations. The cytochrome P450 inhibitor 17-ODYA (0.3-3x10 (-6) M) did not inhibit myogenic tone. Conclusions: No evidence was found f or a role of gadolinium-sensitive, stretch-activated cation channels or cyt ochrome P450 metabolites. On the other hand, both PLC and PKC contribute to the maintenance of myogenic tone. (C) 1999 Elsevier Science B.V. All right s reserved.