Calcium and activation of the release of endothelium-derived relaxing factor.
Indirect and direct experimental evidence demonstrates that both the entry of extracellular calcium and the liberation of calcium from intracellular stores can contribute to an increase in free cytoplasmic calcium concentration in endothelial cells, which seems to be an essential step in the synthesis and/or release of endothelium-derived relaxing factors(s). A variety of Ca2+ transport mechanisms may be involved in the regulation of cytoplasmic calcium in endothelial cells. Ca2+ entry may occur via voltage-operated Ca2+ channels. If they do exist, these channels may have characteristics different from those in underlying vascular smooth muscle cells. Sustained activation of the release of EDRF by various receptor agonists (e.g., acetylcholine, adenine nucleotides, and bradykinin) is also dependent on Ca2+ entry, but it is insensitive to organic Ca2+ channel antagonists. These findings indicate that, when used clinically in various cardiovascular diseases, organic calcium channel antagonists are not expected to interfere with endothelium-dependent relaxation evoked by endogenous vasoactive substances (e.g., ADP, serotonin). Since amiloride and its analogues blocked endothelium-dependent relaxations in different arterial preparations, Na+ transport and Na+/Ca2+ exchange were suggested to play a role in calcium-dependent release of EDRF. The exact nature of Ca2+ transport mechanisms and also the calcium-sensitive cellular processes that lead to the synthesis/release of endothelium derived relaxing factor(s) remain to be determined. However, the available data suggest that calcium handling by the vascular smooth muscle and endothelial cells may be different, allowing potentially selective modulation of Ca2+ activation in these two cell types.
Rubanyi
G M
GM
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota 55905.
Vanhoutte
P M
PM
D000818:Animals; D001688:Biological Products / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D009569:Nitric Oxide; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism
D001688:Biological Products; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D009569:Nitric Oxide; D012964:Sodium; D011188:Potassium; D002118:Calcium