Article
Hydrochlorothiazide attenuates agonist-induced vasoconstriction by affecting Rho kinase
Hydrochlorothiazid schwächt die durch Agonisten induzierte Vasoconstriction durch Einfluss auf die Rho kinase
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Published: | August 10, 2005 |
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Objective: Lowering blood pressure using hydrochlorothiazide has been proven to be effective in clinical studies. The mechanisms by which hydrochlorothiazide lowers blood pressure is still poorly understood
Methods: To evaluate whether hydrochlorothiazide causes calcium desensitization in smooth muscle cells we measured its effects on agonist-induced increase of blood pressure in Wistar rats in vivo, and on agonist-induced vasoconstriction of aortic rings, RhoA, Rho kinase, and intracellular calcium in vascular smooth muscle cells in vitro.
Results: Hydrochlorothiazide significantly attenuated angiotensin II-induced increase of systolic blood pressure in rats from 26±17 mmHg to 2±1 mmHg (mean±SD, n=5, p<0.05). Hydrochlorothiazide inhibited agonist-induced vasoconstriction of aortic rings in a concentration-dependent manner. The incubation of segments from rat aorta with 1 µmol/L hydrochlorothiazide significantly reduced the angiotensin II-induced vasoconstriction to 22±18% (n=6; p<0.01). The inhibitory effect of hydrochlorothiazide was observed both in the presence and absence of endothelium. RT-PCR and immunoblotting showed that RhoA and Rho kinase were significantly reduced in vascular smooth muscle cells after administration of hydrochlorothiazide to 38±17% and to 36±3%, respectively (p<0.05). Agonist-induced changes of intracellular calcium were not affected by hydrochlorothiazide.
Conclusion: The study indicates that hydrochlorothiazide inhibits agonist-induced vasoconstriction by calcium desensitization in smooth muscle cells linked to the Rho kinase pathway