P581Ca: contribution to the spontaneous myogenic response and to agonist evoked contractions2+: contribution to the spontaneous myogenic response and to agonist evoked contractions sensitivity of smooth muscle constriction: contribution to the spontaneous myogenic response and to agonist evoked contractions

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Abstract

Purpose

Vascular contraction is determined by the intracellular Ca2+ concentration and by the Ca2+ sensitivity of smooth muscle cells. Here we made an effort to determine these parameters upon physiological contractions to stretch (spontaneous myogenic response) and to agonists (KCl, serotonin, U46619) in the basilar artery of the rat.

Methods

Isometric contractions and intracellular Ca2+ concentrations Ca2+ directly measured (by force transducer and Ca2+ imaging system) while Ca2+ sensitivity of contraction was calculated.

Results

A linear relationship was found between stretch levels and intracellular Ca2+ concentrations. Rho-kinase inhibition (but not protein kinase C inhibition) antagonized the development and maintenance of the spontaneous myogenic tone. Contractile responses to KCl were mediated by increasing intracellular Ca2+ concentrations, without changes in Ca2+ sensitivity. In contrast, serotonin contractions were accompanied by a 2.5-fold increase in Ca2+ sensitivity, thromboxane A2 receptor stimulation (U46619 treatment) resulted in a limited increase in intracellular Ca2+ concentrations, but a 5-fold increase in Ca2+ sensitivity. Increases in Ca2+ sensitivity were mediated by protein kinase C and Rho-kinase.

Conclusion

Stretch not only increases intracellular Ca2+ concentrations, but also increases the Ca2+ sensitivity of vascular smooth muscle cells. Moreover, agonist stimuli may constrict vessels without affecting (e.g. KCl) or dominantly acting by increasing the intracellular Ca2+ sensitivity (e.g. U46619). These data suggest a dominant role for intracellular Ca2+ sensitivity of force production and identify Rho kinase as a potential target to control blood pressure and distribution.

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