Evidence of an altered in vivo vascular cell turnover in spontaneously hypertensive rats and its modulation by long-term antihypertensive treatment

The aims of this study were to measure in vivo cell turnover in the thoracic aorta from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and to investigate how it could be modulated by chronic antihypertensive treatment. Cell turnover was estimated in rats in which DNA had been prelabeled in utero with [H-3]-thymidine, by the rate of disappearance of total [H-3]-DNA from birth to 20 weeks of age. In SHR compared with WKY. neonatal relative aortic mass was transiently elevated and was reversed to hypotrophy at 8 weeks. At 20 weeks of age, aortic hypertrophy reappeared. Aortic DNA content reflected the morphologic changes observed with age. In both SHR and WKY, the decline with time in [H-3]-prelabeled aortic DNA coupled with the increase in total organ DNA demonstrated that cells prelabeled in utero died and were replaced. Decline in [H-3]-DNA from birth to 8 weeks of age was approximately threefold faster in the aorta from SHR than in WKY. In older SHR, the decrease in [H-3]-DNA was then slower and similar to that of WKY. Chronic treatment of SHR for 15 weeks from the age of 5 weeks, with hydralazine, enalapril, or nifedipine prevented the rise in systolic blood pressure, aortic mass, and DNA content. This was associated with an unchanged residual radioactivity of [H-3]-prelabeled aortic DNA over time, suggesting that the treatment did not stimulate cumulative cell death. We propose that the altered cell turnover is a component of aortic remodeling observed in hypertension. Our data also suggest that it is possible to modulate in vivo cell turnover and affect vascular remodeling by pharmacologic therapy.