ANNEXIN-II INHIBITION OF G-PROTEIN-REGULATED INOSITOL TRISPHOSPHATE FORMATION IN RAT AORTIC SMOOTH-MUSCLE

Vasoconstrictor hormones contribute to the pathogenesis of hypertensio n through intracellular signals that stimulate vascular smooth muscle (VSMC) contraction and/or growth. We previously showed that the glucoc orticoid dexamethasone (DEX) inhibited angiotensin II-stimulated inosi tol trisphosphate (IP3) formation in VSMC, but the mechanism of inhibi tion is not known. Because glucocorticoids stimulate the expression of annexins and annexin II potently binds phosphoinositides, the role of DEX and annexin II in VSMC G protein-coupled phosphoinositide hydroly sis was investigated. DEX incubation blunted increases in guanosine 5' -O-(3-thiotriphosphate) (GTP gamma S)-stimulated IP3 generation and an giotensin II-induced intracellular Ca2+ mobilization but stimulated el evations in VSMC annexin II content. VSMC incubation with exogenous pu rified annexin II resulted in concentration-dependent decreases in GTP gamma S-stimulated IP3 formation. In DEX-treated cells, exogenous ann exin II did not further diminish GTP gamma S-stimulated IP3 formation, suggesting that endogenous annexin II may be a mediator of DEX-induce d inhibition of G protein-coupled IP3 generation. These data represent the first direct evidence of G protein-dependent phosphoinositide hyd rolysis regulation by glucocorticoids or annexins. We speculate that a nnexin II may play a role in the pathogenesis of hypertension through stimulation of VSMC growth.