Role of Rho-associated protein kinase in tone and calcium sensitivity of cannulated rat mesenteric small arteries

The regulation of vascular tone includes modulation of contractile element calcium sensitivity. We tested the involvement of the Rho-associated protei n kinase p160ROCK in tone and calcium sensitivity of cannulated rat mesente ric small arteries. These vessels developed basal tone and showed myogenic responses upon pressure steps, resulting from an increase in calcium in com bination with a high contractile element calcium sensitivity. Y-27632, beli eved to be a specific p160ROCK inhibitor, caused concentration-dependent in hibition of basal tone, with near full inhibition at 3 muM. At this concent ration, myogenic responses were absent and stepwise pressure elevation resu lted in severe vascular distension. Y-27632 did not affect pressure-induced changes in intracellular calcium but rather reduced pressure-induced as we ll as phenylephrine-induced calcium sensitisation. Thus in the presence of the blocker, for a given calcium concentration, tone was greatly reduced, a nd the divergence in sensitivity between pressure and phenylephrine as stim uli on the one hand and potassium on the other disappeared. K+ (125 mm) and ionomycin still caused contraction in the presence of the p160ROCK blocker . These data show that in pressurised small arteries the Rho-p160ROCK pathw ay is active in the absence of vasoconstrictors, keeping the vessels in a s tate of high calcium sensitivity and basal tone.