Effect of antihypertensive therapy on the vascular changes of spontaneously hypertensive rats

The effect of antihypertensive therapy on vascular morphologic characteristics was studied in spontaneously hypertensive rats (SHRs). Starting at either 7 or 22 weeks of age, SHRs were given a combination of hydralazine, chlorothiazide, and reserpine, which reduced the blood pressure significantly below the level of untreated animals. Rats were sacrificed at either the 22nd or the 42nd week of age along with age-matched untreated SHRs and normotensive Wistar-Kyoto controls. The following treatment groups were thus obtained: a) treated from the 7th to the 22nd or 42nd week, b) treated from the 22nd to the 42nd week, and c) treated from the 7th to the 22nd and left untreated until the 42nd week. Ultrastructural and morphometric studies were carried out on the aorta and intrarenal vessels. The expansion of the subendothelial space and medial thickening in the aorta as well as the increase in external to luminal diameter ratios and wall thickness of intrarenal vessels were prevented in SHRs treated continuously from the 7th week on. The severity of vascular lesions was markedly reduced in animals treated from the 22nd to 42nd week. Discontinuation of therapy resulted in rapid reestablishment and progression of both aortic and renal vascular disease to a degree identical to that of untreated SHRs. The results indicate that hypertensive vascular changes are preventable by early treatment and, depending on their nature, can be arrested or reversed by delayed treatment.