Abstract
The purpose of this study was to determine the mechanism responsible for alterations in NaF-induced contractions of blood vessels from streptozotocin-induced diabetic rats. In the presence of AlCl3, NaF (≥7.5 mM) produced significantly greater contractions in diabetic aorta and mesenteric artery compared with age-matched controls. Pretreatment with 1 μM nifedipine eliminated the enhanced contractile responses of diabetic vessels to NaF, resulting in no difference in the magnitude of NaF-induced contractions between control and diabetic vessels. In the presence of 100 μM deferoxamine, an Al3+ chelator, NaF-induced contractions of diabetic vessels were markedly attenuated, whereas only the responses to lower concentrations of NaF were reduced in control vessels. No significant difference was found in the peak amplitude of transient contractions induced by 10 μM cyclopiazonic acid between control and diabetic vessels. The addition of 10 μM okadaic acid produced attenuated contractions in diabetic vessels. These findings indicate no involvement of the inhibitory effects of NaF on endoplasmic reticular Ca2+-pump ATPase and protein phosphatases in the genesis of the enhanced responsiveness of diabetic vessels to NaF. Western blot analysis showed a 2.5-fold increase in the expression of Gqα in diabetic aortic membranes. In contrast, the Giα level was modestly decreased and the Gsα and Gβγ levels were unchanged in diabetes. The present results suggest that enhanced vascular contractions to NaF in diabetes is attributed predominantly to a G protein-mediated Ca2+ channel activation that results from markedly increased Gqα expression in vascular tissues under this pathological state.
Footnotes
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Send reprint requests to: Yuichi Hattori, M.D., Department of Pharmacology, Hokkaido University School of Medicine, Sapporo 060-8638, Japan. E-mail:yhattori{at}med.hokudai.ac.jp
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1 This work was supported in part by a Grant-in-Aid for Science Research from the Ministry of Education, Sports, and Culture of Japan.
- Abbreviations:
- CPA
- cyclopiazonic acid
- PSS
- physiological salt solution
- PVDF
- polyvinylidene difluoride
- Received April 20, 1999.
- Accepted November 9, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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