Chronic alpha 1-adrenoreceptor stimulation increases DNA synthesis in rat arterial wall. Modulation of responsiveness after vascular injury.

ABSTRACT

Despite indirect evidence from studies using adrenergic antagonists or sympathectomy, catecholamines have never been shown directly to stimulate vascular smooth muscle cell (SMC) DNA replication in vivo. We studied whether a chronic infusion of catecholamine stimulates SMC replication in vivo in both uninjured arteries and arteries with a neointima formed after vascular injury. Animals were killed after 2 weeks of continuous infusion of bromodeoxyuridine (to label replicating DNA) and either phenylephrine, norepinephrine, or vehicle solution, starting early (third week) or late (ninth week) after balloon injury to the left common carotid artery. In catecholamine-infused animals, the uninjured carotid artery or thoracic aorta showed a marked increase in cross-sectional area (> 25%) and frequency of cells undergoing DNA synthesis among medial SMCs (4- to 10-fold) and endothelial cells (13-fold). With catecholamine infusion at 9 to 10 weeks after injury, the media or neointima of the injured carotid artery showed a smaller increase in SMC DNA replication (< or = 4-fold) than did the normal arterial media. In contrast, catecholamine infusion at 3 to 4 weeks did not cause significant SMC growth in the injured vessel. Catecholamine infusion caused labile elevations of systolic blood pressure. Taken together with our previous observation that alpha 1-blockers suppress arterial SMC replication without preventing severe hypertension in the rat, the present data strongly suggest that alpha 1-adrenoreceptors stimulate SMC DNA synthesis in vivo in arteries with or without intimal thickening, although not during the first weeks after balloon injury. The stimulation of DNA synthesis in vascular cells via the alpha 1-adrenoreceptor pathway may contribute to the vascular remodeling that occurs in hypertension and atherosclerosis.