Alteration of the [Ca(2+)](i)-force relationship during the vasorelaxation induced by a Ca(2+) channel blocker SR33805 in the porcine coronary artery.
The mechanism of vasorelaxation induced by SR33805 was investigated by simultaneously monitoring the cytosolic Ca(2+) concentration ([Ca(2+)](i)) and force, and by determining level of myosin light chain (MLC) phosphorylation in the medial strip of the porcine coronary artery. SR33805 inhibited the sustained increases in [Ca(2+)](i) and force (IC(50); 3.2+/-1.0 and 49.4+/-27.5 nM, respectively) induced by 118 mM K(+)-depolarization. There was about a 10 fold difference in the inhibitory potency between [Ca(2+)](i) and force. SR33805 completely inhibited the [Ca(2+)](i) elevation induced by a thromboxane A(2) analogue, U46619 and histamine, at concentrations (1 microM) higher than those required for the complete inhibition of K(+)-depolarization induced [Ca(2+)](i) elevation. SR33805 had no effect on the [Ca(2+)](i) elevation induced by histamine or caffeine in the absence of extracellular Ca(2+). SR33805 caused a leftward shift of the [Ca(2+)](i)-force relationship of the contraction induced by cumulative application of extracellular Ca(2+) during 118 mM K(+)-depolarization. The relationship between [Ca(2+)](i) and MLC phosphorylation also shifted to the left by SR33805, while the relationship between MLC phosphorylation and force remained unaffected. In conclusion, SR33805 caused an apparent leftward shift of the [Ca(2+)](i)-force relationship, accompanied by a greater degree of MLC phosphorylation for a given level of [Ca(2+)](i). The mechanism of this leftward shift, however, still remains to be elucidated.
Ieiri
S
S
Department of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1- Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
Hirano
K
K
Nishimura
J
J
Suita
S
S
Kanaide
H
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D018994:Myosin Light Chains / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology*; D013552:Swine; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D002121:Calcium Channel Blockers; D007211:Indoles; D018994:Myosin Light Chains; D013450:Sulfones; D014662:Vasoconstrictor Agents; C084255:SR 33805; D002110:Caffeine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D006632:Histamine; D011188:Potassium; D002118:Calcium