Activation of nitric oxide modulator effect by isometric contraction in rat resistance arteries

The participation of nitric oxide (NO) as a modulator of the isometric contraction, as well as the underlying mechanism, was investigated in rat small mesenteric arteries. In the presence of a functional endothelium, L-NAME and L-NA similarly increased the contractions induced by phenylephrine, dependently on the level of contraction. However, no effect was observed in the absence of a functional endothelium. In the presence of selective inhibitors of protein kinase C (PKC) and phosphatidyl-inositol 3-kinase (PI3K), calphostin-C and wortmannin, respectively, the effect of L-NAME was not modified. The same observation was done in the presence of the tyrosine kinase inhibitors, genistein and tyrphostin A-23. However, in the presence of a Ca2+-independent tyrosine kinase inhibitor, erbstatin-A, and on the presence of a non-selective kinase inhibitor, staurosporine, a strong reduction was observed. Our results suggest that protein kinases are involved in the activation of nitric oxide modulator effect on isometric contractions in resistance arteries.