Effects of an Angiotensin II Receptor Antagonist, CV-11974, on Angiotensin II-Induced Increases in Cytosolic Free Calcium Concentration, Hyperplasia, and Hypertrophy of Cultured Vascular Smooth Muscle Cells
| Autor: | Keisuke Fukuo, T Nabata, Hiromi Rakugi, Jun Tomita, Eio Koh, Takuo Inoue, Shigeto Morimoto, Bingbing Jiang, Toshio Ogihara |
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| Rok vydání: | 1994 |
| Předmět: |
medicine.medical_specialty
Angiotensin receptor Vascular smooth muscle Muscle Proteins Tetrazoles chemistry.chemical_element Aorta Thoracic Angiotensin II receptor antagonist Biology Calcium Dinoprost Muscle Smooth Vascular Muscle hypertrophy Angiotensin Receptor Antagonists Cytosol Internal medicine medicine Animals Rats Wistar Cells Cultured Pharmacology Hyperplasia Angiotensin II receptor type 1 Angiotensin II Ionomycin Biphenyl Compounds DNA Hypertrophy medicine.disease Rats Endocrinology chemistry cardiovascular system Benzimidazoles Fura-2 Cardiology and Cardiovascular Medicine |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0160-2446 |
| Popis: | The effects of CV-11974, a potent nonpeptide antagonist of the angiotensin II (AII) type-1 receptor (AT1), on cytosolic free calcium concentration ([Ca2+]i), hyperplasia, and hypertrophy of cultured vascular smooth muscle cells (VSMC) from rat aorta were studied. [Ca2+]i was measured by fura 2, and hyperplasia and hypertrophy were determined by incorporation of [3H]thymidine and [3H]leucine, respectively. CV-11974 had no effect on [Ca2+]i itself, but suppressed 10(-7) M AII-induced increase in [Ca2+]i dose dependently at concentrations from 10(-10) M and completely at 10(-7) M. CV-11974 suppressed both Ca2+ release from intracellular Ca2+ stores and Ca2+ influx from the extracellular space. However, CV-11974 had no effect on the increases in [Ca2+]i induced by prostaglandin F2 alpha (PGF2 alpha), a potent vasoconstrictor, or ionomycin, a Ca2+ ionophore. These results indicate that the suppressive effects of CV-11974 act on the binding of AII and its specific receptors. AII 10(-7) M increased the synthesis of DNA and protein to 1.5 and 1.7 times the control values, respectively. CV-11974 had no effect on synthesis of DNA or protein, but suppressed the AII-stimulated synthesis of DNA and protein dose dependently at concentrationsor = 10(-8) and 10(-10) M, respectively and completely at 10(-6) M. These results indicate that AII increases [Ca2+]i and synthesis of DNA and protein in VSMC through activation of AT1. CV-11974 showed no partial agonistic effects on AII. Thus, CV-11974 may act not only as an antihypertensive agent, but also as an inhibitor of vascular injury stimulated by AII. |
| Databáze: | OpenAIRE |
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