Proliferative response of smooth muscle cells in hypertension.

Abstract

A significant increase (up to 20% from about 10% in normals) in the number of smooth muscle cells (SMC) with tetraploid DNA content was found in the media and intima of human hypertensive aorta. A similar process was detected during normal human vessel aging. It was found that SMC from normal human aorta and normotensive rat aorta, which were able to incorporate 3H-thymidine, had diminished proliferative potency and a tendency to polyploidization in primary culture. We failed to detect a similar phenomenon in SMC obtained from aorta from spontaneously hypertensive rats. It was found that 10 mumol/L of norepinephrine significantly increased (by approximately twofold) the frequency of true polyploid cells in a subculture of rat aortic SMC. The effect of norepinephrine was blocked only by simultaneous action of alpha- and beta-adrenoreceptor antagonists. SMC polyploidization was also stimulated by simultaneous application of two direct activators of the second messenger systems, forskolin and phorbol-12-myristate-13-acetate. Thus, a subpopulation of SMC prone to polyploidization exists in normal vessels, and norepinephrine may be one of the mediators of the "hypertensive" response of vessel wall SMC, which probably occurs due to the synergism of two second messenger systems.