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 protein kinase p160ROCK in tone and calcium sensitivity of cannulated rat mesenteric small arteries. These vessels developed basal tone and showed myogenic responses upon pressure steps, resulting from an increase in calcium in combination with a high contractile element calcium sensitivity. Y-27632, believed to be a specific p160ROCK inhibitor, caused concentration-dependent inhibition of basal tone, with near full inhibition at 3 microM. At this concentration, myogenic responses were absent and stepwise pressure elevation resulted in severe vascular distension. Y-27632 did not affect pressure-induced changes in intracellular calcium but rather reduced pressure-induced as well as phenylephrine-induced calcium sensitisation. Thus in the presence of the blocker, for a given calcium concentration, tone was greatly reduced, and the divergence in sensitivity between pressure and phenylephrine as stimuli 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 pathway is active in the absence of vasoconstrictors, keeping the vessels in a state of high calcium sensitivity and basal tone.
VanBavel
E
E
Academic Medical Center, University of Amsterdam, Department of Medical Physics, PO Box 22700, 1100 DE Amsterdam, The Netherlands. e.vanbavel@amc.uva.nl
van der Meulen
E T
ET
Spaan
J A
JA
D000577:Amides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004347:Drug Interactions; D047908:Intracellular Signaling Peptides and Proteins; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009119:Muscle Contraction; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D009129:Muscle Tonus; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D054460:rho-Associated Kinases
D000577:Amides; D047908:Intracellular Signaling Peptides and Proteins; D007476:Ionophores; D009125:Muscle Relaxants, Central; D011725:Pyridines; D014662:Vasoconstrictor Agents; C108830:Y 27632; D010656:Phenylephrine; D015759:Ionomycin; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D011188:Potassium; D002118:Calcium