title: Evidence of an altered in vivo vascular cell turnover in spontaneously hypertensive rats and its modulation by long-term antihypertensive treatment.
abstract: 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 [ 3 H]-thymidine, by the rate of disappearance of total [ 3 H]-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 [ 3 H]-prelabeled aortic DNA coupled with the increase in total organ DNA demonstrated that cells prelabeled in utero died and were replaced. Decline in [ 3 H]-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 [ 3 H]-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 [ 3 H]-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.
authors.affiliation: Research Centre, University of Montreal Health Centre-Hôtel Dieu, University of Montreal, Montreal, Quebec, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Thorin-Trescases
authors.forename: D
authors.initials: D
authors.lastname: deBlois
authors.forename: P
authors.initials: P
authors.lastname: Hamet
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002250:Carbon Radioisotopes; D016923:Cell Death; D004247:DNA / Q000032:analysis / Q000096:biosynthesis; D053938:DNA Fragmentation; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D006984:Hypertrophy / Q000517:prevention & control; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013936:Thymidine / Q000031:analogs & derivatives* / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
chemical_list: D000959:Antihypertensive Agents; D002250:Carbon Radioisotopes; D014316:Tritium; D004247:DNA; C012439:methylthymidine; D013936:Thymidine