Role of calcium and endothelium in hypertension, cardiovascular disease, and subsequent vascular events.
The response of isolated blood vessels to vasoactive agonists is modulated by endothelial cells. Nitric oxide is probably the major endothelium-derived relaxing factor (EDRF), although an unidentified hyperpolarizing factor and prostacyclin are secreted. Previous studies indicate that the release of EDRF must require an increase in cytoplasmic calcium in the endothelial cells. In perfused arteries, calcium-channel activators also trigger the release of EDRF; thus, the endothelial cell membrane must contain voltage-operated calcium channels. However, the increase in cytoplasmic calcium stimulating EDRF release is not due to activation of these channels. Endothelial cells also release constricting factors (EDCF), most likely superoxide anions, endoperoxides, and endothelin. Endothelium-dependent contractions can be evoked by anoxia. These contractions, as well as the endothelium-dependent increases in tension evoked by stretch in cerebral arteries, are inhibited by calcium antagonists. This inhibitory effect is at the level of vascular smooth muscle, not the endothelium. Thus, calcium antagonists do not prevent the release of either EDRF or EDCF. Indeed, by facilitating the inhibition exerted by the former and preventing the activation of vascular smooth muscle by the latter, they favor dilation.
Vanhoutte
P M
PM
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas 77030-3498.
D002118:Calcium / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000209:etiology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000209:etiology*
D002118:Calcium