Predominant contribution of the G protein-mediated mechanism to NaF-induced vascular contractions in diabetic rats: Association with an increased level of G(q alpha) expression

The purpose of this study was to determine the mechanism responsible for al terations in NaF-induced contractions of blood vessels from streptozotocin- induced diabetic rats. In the presence of AlCl3, NaF (greater than or equal to 7.5 mM) produced significantly greater contractions in diabetic aorta a nd mesenteric artery compared with age-matched controls. Pretreatment with 1 mM nifedipine eliminated the enhanced contractile responses of diabetic v essels to NaF, resulting in no difference in the magnitude of NaF-induced c ontractions between control and diabetic vessels. In the presence of 100 mu M deferoxamine, an Al3+ chelator, NaF-induced contractions of diabetic ves sels were markedly attenuated, whereas only the responses to lower concentr ations of NaF were reduced in control vessels. No significant difference wa s found in the peak amplitude of transient contractions induced by 10 mu M cyclopiazonic acid between control and diabetic vessels. The addition of 10 mM okadaic acid produced attenuated contractions in diabetic vessels. Thes e findings indicate no involvement of the inhibitory effects of NaF on endo plasmic reticular Ca2+-pump ATPase and protein phosphatases in the genesis of the enhanced responsiveness of diabetic vessels to NaF. Western blot ana lysis showed a 2.5-fold increase in the expression of G(q alpha) in diabeti c aortic membranes. In contrast, the G(i alpha) level was modestly decrease d and the G(s alpha) and G(beta gamma) levels were unchanged in diabetes. T he present results suggest that enhanced vascular contractions to NaF in di abetes is attributed predominantly to a G protein-mediated Ca2+ channel act ivation that results from markedly increased Gqa expression in vascular tis sues under this pathological state.