Thiazide-Like Diuretics Attenuate Agonist-Induced Vasoconstriction by Calcium Desensitization Linked to Rho Kinase
| Autor: | Tingbing Cao, Martin Tepel, Shanjun Zhu, Zhiming Zhu, Daoyan Liu, Lijuan Wang |
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| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Vascular smooth muscle Sodium Chloride Symporter Inhibitors medicine.medical_treatment Myocytes Smooth Muscle Drug Resistance Muscle Proteins chemistry.chemical_element Blood Pressure In Vitro Techniques Protein Serine-Threonine Kinases Calcium Muscle Smooth Vascular Norepinephrine Internal medicine Internal Medicine medicine Animals Vasoconstrictor Agents Rats Wistar Diuretics Rho-associated protein kinase Antihypertensive Agents Aorta Thiazide rho-Associated Kinases Chemistry Angiotensin II Intracellular Signaling Peptides and Proteins Chlorthalidone DNA Intracellular Membranes Rats Hydrochlorothiazide Endocrinology Vasoconstriction Rho kinase inhibitor medicine.symptom Diuretic Acute-Phase Proteins medicine.drug |
| Zdroj: | Hypertension. 45:233-239 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | Lowering blood pressure using thiazide-like diuretics, including chlorthalidone and hydrochlorothiazide, has been proven to be effective in clinical studies. However, the mechanisms by which thiazide-like diuretics lower blood pressure are still poorly understood. To evaluate whether thiazide-like diuretics cause calcium desensitization in smooth muscle cells, we measured their effects on agonist-induced increase of blood pressure in Wistar rats in vivo and on agonist-induced vasoconstriction of aortic rings, DNA synthesis, and protein synthesis, RhoA, Rho kinase, and intracellular calcium in vascular smooth muscle cells in vitro. Thiazide-like diuretics significantly attenuated angiotensin II–induced or norepinephrine-induced increase of systolic blood pressure in rats. Thiazide-like diuretics inhibited agonist-induced vasoconstriction of aortic rings in a concentration-dependent manner in the presence and absence of endothelium. The inhibitory effects of thiazide-like diuretics were similar to that of the specific Rho kinase inhibitor Y27632. RT-PCR and immunoblotting showed that RhoA and Rho kinase were significantly reduced in vascular smooth muscle cells after administration of thiazide-like diuretics. In contrast, thiazide-like diuretics did not affect protein tyrosine phosphatase-2 (SHP-2) expression. Agonist-induced changes of intracellular calcium were not affected by thiazide-like diuretics. The study indicates that thiazide-like diuretics inhibit agonist-induced vasoconstriction by calcium desensitization in smooth muscle cells linked to the Rho–Rho kinase pathway. |
| Databáze: | OpenAIRE |
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