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VANADYL SULFATE INHIBITS NO PRODUCTION VIA THREONINE PHOSPHORYLATION OF ENOS
Citation:
Carter, J, L. A. Dailey, J M. Soukup, Huang, YuhChin T, AND Z. Li. VANADYL SULFATE INHIBITS NO PRODUCTION VIA THREONINE PHOSPHORYLATION OF ENOS. ENVIRONMENTAL HEALTH PERSPECTIVES 112(2):201-206, (2004).
Impact/Purpose:
Shows exposure to excessive vanadium (V) occurs in some occupations and with consumption of some dietary regimens for weight reduction and body-building.
Description:
Exposure to excessive vanadium (V) occurs in some occupations and with consumption of some dietary regimens for weight reduction and body-building. Because vanadium is vasoactive, individuals exposed to excessive V may develop adverse vascular effects. We showed previously that vanadyl sulfate (VOSO4) causes acute pulmonary vasoconstriction, which could be attributed in part to inhibition of NO production. The present study investigated the mechanisms for NO inhibition related to altered NOS activity and enhanced superoxide (O2-) production. VOSO4 produced dose-dependent constriction of pulmonary artery in isolated perfused lungs and pulmonary arterial rings and a right shift of acetylcholine-dependent vasorelaxation curve. In intact lungs and human pulmonary artery endothelial cells, VOSO4 inhibited NO production acutely. This was accompanied by increased Thr495 phosphorylation of eNOS, which would inhibit eNOS activity. Thr495 phosphorylation of eNOS and NO inhibition were partially reversed by pretreatment with calphostin C, a protein kinase C (PKC) inhibitor, and A23187, a calcium ionophore. There were no changes in Ser1177 or tyrosine phosphorylation of eNOS. VOSO4 also enhanced O2- production that was inhibitable by SOD and diphenyleneiodonium. These two O2- inhibitors attenuated VOSO4-induced pulmonary hypertension but had little effect on VOSO4-induced NO inhibition. These results indicate that VOSO4 induced acute pulmonary vasoconstriction that was mediated by at least two mechanisms: inhibition of endothelial NO production and overproduction of O2-. NO inhibition was partially mediated by PKC-dependent phosphorylation of Thr495 of eNOS. Exposure to excessive V may contribute to pulmonary vascular diseases.