The contractile mechanism of sodium metavanadate in isolated rat aortae

The mechanism of contractile effect of vanadate was investigated in rat aortae. Sodium metavanadate (NaVO3; 10(-5)-3 x 10(-3) M) induced contractile responses in a concentration-dependent manner. Removal of endothelium did not affect the response to NaVO3. The response to NaVO3 was inhibited by nifedipine, a voltage-operated Ca2+ channel (VOC) inhibitor; NCDC, a phospholipase C inhibitor; and H-7, a protein kinase C inhibitor, but not by prazosin, an alpha1-adrenoceptor antagonist; methysergide, a serotonin-receptor antagonist; tripelennamine, a histamine-receptor antagonist; glibenclamide, an adenosine triphosphate (ATP)-dependent K+-channel inhibitor; or iberiotoxin, a large-conductance Ca2+-activated K+-channel inhibitor. In addition, genistein or tyrphostin A48, tyrosine kinase inhibitors, did not affect the contraction induced by NaVO3. Mg2+ removal or antimycin A, a Ca2+-ATPase inhibitor, did not cause any contraction. Ouabain, a Na+, K+-ATPase inhibitor, or K+-free medium caused the contraction of the aortae. The maximal contraction induced by NaVO3 plus ouabain was similar to that induced by NaVO3 alone. In addition, the response to NaVO3 was inhibited by AA861, a 5-lipoxygenase inhibitor, and RHC-80267, a diacylglycerol (DAG) lipase inhibitor. In the presence of AA861, either H-7 or nifedipine further inhibited the residual response to NaVO3. In the presence of NCDC, however, AA861 failed further to affect the residual response to NaVO3. In rat aortae, NaVO3 increased the levels of inositol monophosphate (IP) and prostaglandin F2alpha (PGF2alpha). AA861 and NCDC inhibited the IP increase. In addition, NCDC inhibited the PGF2alpha increase. These results suggest that the response to NaVO3 in rat aortae may be mainly the result of the increased phosphoinositide metabolism.