Dipyridamole inhibits intracellular calcium transients in isolated rat arteriole smooth muscle cells.
Dipyridamole, an inhibitor of adenosine uptake as well as a cGMP phosphodiesterase inhibitor, is commonly used in prophylactic therapy for patients with angina pectoris. However, the effects of dipyridamole on systemic blood vessels, especially on the peripheral vascular system, are not well understood. Therefore, the effect of dipyridamole on ATP-induced arteriole contraction was examined with special reference to intracellular Ca(2+) concentration ([Ca(2+)](i)) using real-time confocal microscopy. In cases of 0.1-10microM range, dipyridamole induced only slight [Ca(2+)](i) decreases in smooth muscle cells of both testicular and cerebral arterioles. However, 100microM dipyridamole induced substantial [Ca(2+)](i) decreases in the cells. In the presence of 10microM dipyridamole, changes in ATP-induced [Ca(2+)](i) were found to be inhibited in smooth muscle cells of testicular arterioles but not in those of cerebral arterioles. In addition, alpha, beta-methylene ATP-induced [Ca(2+)](i) increases in testicular arteriole smooth muscle cells were also partially inhibited in the presence of dipyridamole. When testicular arterioles were perfused with dipyridamole, no increases in nitric oxide levels were detected. High levels of K(+) induced a [Ca(2+)](i) increase in testicular arterioles that was also partially inhibited by dipyridamole. In the presence of substances that affect protein kinase A or G, ATP-induced [Ca(2+)](i) was not completely inhibited. These findings suggest that dipyridamole may act not only as an inhibitor of adenosine uptake and as a cGMP phosphodiesterase inhibitor, but also as a calcium channel blocker in arteriole smooth muscle cells.
Department of Anatomy, Iwate Medical University School of Medicine, Uchimaru, Morioka, Japan. tsaino@iwate-med.ac.jp
Tomoyuki
T
Saino
Toshinari
T
Misaki
Makoto
M
Matsuura
Toshiki
T
Shikanai
Yoh-ichi
Y
Satoh
D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D004176:Dipyridamole / Q000494:pharmacology*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D011913:Rats, Inbred BB; D013737:Testis / Q000098:blood supply / Q000166:cytology
D004176:Dipyridamole; D002118:Calcium