Sympathetic drive and vascular damage in hypertension and atherosclerosis

Abstract

Current knowledge of the links between the sympathetic nervous system and vascular damage in hypertension and atherosclerosis is summarized. The main mechanisms leading to the structural changes of the arterial wall as a consequence of enhanced adrenergic drive are reported. Hemodynamic mechanisms, including increase in pressure leading to changes in the arterioles and alteration of flow pattern with impact mainly in the large arteries, respectively, account for the typical target organ damage observed in hypertension and is involved in the development of atherosclerotic lesions. Regarding the direct effect of catecholamines, the atherogenic effects of epinephrine and norepinephrine in the absence of changes in blood pressure and cholesterol levels have been demonstrated in vivo in monkeys and rabbits. In rats, catecholamine administration induces polyploidization of aortic smooth muscle cells in vivo and in vitro. Regarding the effects of lipid metabolism, adrenergic stimulation may induce free fatty acid transformation into triglycerides with secondary increase in very low density lipoprotein plasma levels and decrease of very low density lipoprotein transformation into high density lipoprotein through circulating lipoprotein lipase inhibition. Catecholamines may also increase cholesterol levels of the arterial wall, probably by triggering the acyl-cholesterol-acyl-transferase activity. Finally, indirect evidence of the pathogenetic role played by the sympathetic system in the development of vascular disease derives from the results of experiments showing that sympatholytic agents are capable of reducing both medial hypertrophy and atherogenesis. beta-Blockers, alpha- and beta-blockers, and centrally acting sympatholytic agents not only ameliorate hemodynamics but also appear to inhibit the direct effects of catecholamines on the arterial wall.