Vascular Regulation in Atherosclerosis

Summary

Physiologically, requirements for increased organ perfusion are met acutely by vasodilation, and chronically by the growth of pre-existent and new vascular channels. Current evidence indicates that the arteriosclerotic circulation undergoes several alterations that limit acute and chronic hyperemic responses. Macrovascular occlusive disease (atheroma, thrombosis) is not the only factor that may limit flow. Vasomotor tone, the sum of dilating and constricting influences, may be altered in favor of constriction, both at the macrovascular and microvascular levels. Major mechanisms that have been demonstrated include sensitization of arterial smooth muscle to specific endogenous constrictors (histamine, serotonin), and impaired endothelium-dependent vasodilation. The latter appears to affect particularly the arterial microcirculation which importantly determines organ perfusion to a large extent. Chronic adjustments include increases in macrovascular arterial diameter, and the generation of new arterial pathways (collateralization, microvasularization, angiogenesis). Recent experiments in our laboratory have demonstrated that arterial growth evoked by chronic increases in arterial flow is dependent on the presence of a normally functioning endothelium. After mechanical de-endothelialization of large arteries, or in the presence of hypercholesterolemic endothelial injury, vascular growth is impaired. Ongoing experiments focusing on the microcirculation further indicate that the growth of new small vessels (angiogenesis) may likewise be impaired in the presence of hypercholesterolemia. The results suggest that atherosclerosis may affect acute and chronic flow adjustments by multiple mechanisms. It is hoped that an understanding of these mechanisms will provide a new basis for the treatment of ischemic syndromes.