Differential effects of antihypertensive drug therapy on vascular smooth muscle cell hypertrophy, hyperploidy, and hyperplasia in the spontaneously hypertensive rat.

Publisher Website
Google Scholar
Abstract
Smooth muscle cell hypertrophy, hyperploidy and hyperplasia were studied in hypertensive and Wistar-Kyoto rats, of 3- and 7-mo.-old, and the effects of antihypertensive drug treatment were explored on the accelerated growth of vascular smooth muscle in aortas of spontaneously hypertensive vs. Wistar-Kyoto rats. Drug-treated rats were administered a combination of reserpine, hydralazine and chlorathiazide in their drinking water, either between 3 and 5 mo. or between 5 and 7 mo. of age. Drug treatment decreased the blood pressure of spontaneously hypertensive rats to values at or below those of Wistar-Kyoto rats for both age-treatment groups. Smooth muscle growth was evaluated by morphometric analyses of aortic smooth muscle content, flow cytometric and microdensitometric measurements of the frequency of polyploid smooth muscle cells, biochemical estimates of aortic medial smooth muscle cell number and microdensitometric measurements of individual smooth muscle cell protein content. Aortic medial smooth muscle content was not significantly increased in 3 mo. spontaneously hypertensive compared to Wistar-Kyoto rats, indicating that aortic smooth muscle hypertrophy occurred post-3 mo., as well as after blood pressure was elevated. In 5-mo. old spontaneously hypertensive and Wistar-Kyoto rats, medial smooth muscle hypertrophy was accounted for by cellular hypertrophy without hyperplasia; in contrast, medial hypertrophy in 7-mo. old spontaneously hypertensive rats involved both cellular hypertrophy and hyperplasia. Antihypertensive treatment prevented the accelerated growth of vascular smooth muscle that occurred in spontaneously hypertensive rats via cellular hypertrophy and hyperploidy, but it did not prevent an increase in smooth muscle cell number in spontaneously hypertensive rats between 5 and 7 mo. of age. It had no effect on the parallel increases in aortic medial smooth muscle cell number that occurred in both spontaneously prevented accelerated development of smooth muscle cell polyploidism in spontaneously hypertensive rats, in no case (spontaneously hypertensive or Wistar-Kyoto rats) did it reverse changes in ploidy that existed at the time of initiation of drug treatment, althouh it did cause cellular atrophy in smooth muscle cells of each ploidy class. Reductions in vascular smooth muscle content with drug treatment were due to reductions in smooth muscle cell size, not to reductions in cell number. The differential effects of blood pressure lowering on hypertrophic vs. hyperplastic smooth muscle cell growth clearly suggests theat the mediating factors for these 2 growth processes are different. Data support the hypothesis that hypertrophic smooth muscle cell growth represents a response to increased blood pressure or wall stress, but suggests that factors other than elevated blood pressure per se are responsible for smooth muscle cell hyperplasia.