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Role of Rho‐Associated Protein Kinase in Tone and Calcium Sensitivity of Cannulated Rat Mesenteric Small Arteries
Author(s) -
VanBavel Ed,
Meulen Esther T.,
Spaan Jos A. E.
Publication year - 2001
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/eph8602217
Subject(s) - calcium , phenylephrine , medicine , mesenteric arteries , endocrinology , voltage dependent calcium channel , calcium channel blocker , chemistry , calcium in biology , anatomy , artery , blood pressure
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 μM. 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.