Inhibitory Effects of Carvedilol on Calcium Channels in Vascular Smooth Muscle Cells.

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概要

• 論文の詳細を見る

• Carvedilol has hypotensive effects and inhibits agonist-induced cell proliferation of vascular smooth muscle and then prevents vascular remodeling. However, the basic mechanisms have not been clarified. We examined the effects of carvedilol on [Ca2+]i mobilization and voltage-dependent L-type Ca2+ current (ICa.L) in vascular smooth muscle cells, and compared them with metoprolol. [Ca2+]i was measured using fura-2 AM and patch clamp techniques in rat embryonic aortic smooth muscle cells (A7r5). In the presence of extracellular Ca2+, vasopressin and endothelin-1 increased [Ca2+]i due first to the Ca2+ release from store sites, and subsequently Ca2+ entry. Carvedilol did not inhibit the Ca2+ release, but significantly suppressed the sustained rise due to Ca2+ entry concentration-dependently. Nifedipine and nicardipine (10 μM) partly inhibited the sustained rise, but carvedilol inhibited it more effectively than the Ca2+ channel blockers. Under voltage clamp conditions, carvedilol (0.2-10 μM) reversibly inhibited the ICa.L concentration-dependently without any changes in the current-voltage relationships of ICa.L. Carvedilol shifted the steady-state inactivation for ICa.L to more negative potentials and inhibited ICa.L in a voltage-dependent manner. In addition, carvedilol did not inhibit Ca2+ release from store sites induced by thapsigargin, but significantly inhibited the sustained rise due to capacitative Ca2+ entry unrelated to ICa.L. In contrast, metoprolol did not mimic these effects of carvedilol. These results provide evidence that carvedilol inhibits ICa.L and may also inhibit the channels for agonist (vasopressin and endothelin-1)-induced Ca2+ entry in vascular smooth muscle cells, which might contribute to the vasorelaxing and antiproliferative effects of carvedilol.

• International Heart Journal刊行会の論文

著者

• Nagai Ryozo

  Cardiovascular Medicine, The University of Tokyo

• Nakajima Toshiaki

  Cardiology Division Jr Tokyo General Hospital:the Second Department Of Internal Medicine University

• Iwasawa Kuniaki

  Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine

• Iida Haruko

  Gastroenterology, University of Tokyo, Graduate School of Medicine

• Ma Ji

  Gastroenterology, University of Tokyo, Graduate School of Medicine

• Omata Masao

  Gastroenterology, University of Tokyo, Graduate School of Medicine

• Jo Taisuke

  Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine

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