ABSTRACTRegression of left ventricular hypertrophy after control of blood pressure has been documented with some antihypertensive agents but not with others. To determine whether similar differences in regression of wall thickening also occur in resistance vessels during treatment, matched groups of spontaneously hypertensive rats (SHR) were treated for 12 weeks with either hydralazine (H) or captopril and hydrochlorothiazide (C-D) and they were compared with untreated SHR and Wistar- Kyoto rats (WKY). Perfusion pressure was then determined in the hindlimbs of pithed rats under conditions of constant blood flow (4.0 ml/min) and maximal vasodilation (hemodilution to 22% hematocrit combined with continuous nitroprusside and papaverine infusion). This perfusion pressure, which has been validated as an index of thickening (hypertrophy) of resistance vessels walls, averaged 26.8 ± 0.4(SE) mm Hg in untreated WKY (n = 12) and 37.6 ± 0.4 mm Hg in untreated SHR (n = 11) (p > .01). Treatment with H or C-D controlled blood pressure equally in SHR, but the two drugs had significantly different effects on both left ventricular hypertrophy and resistance vessels. Perfusion pressure was reduced from 37.6 ± 0.4 mm Hg to 34.0 + 0.5 mm Hg (p > .01) with C-D but only to 36.5 ± 0.5 mm Hg with H (NS). Left ventricular weight was significantly reduced by C-D (2.02 + 0.02 vs 2.63 + 0.05 mg/g, p > .01) but only to 2.44 ± 0.05 mg/g by H. Close correlations were found both before and after treatment, between perfusion pressure and left ventricular weight (y = 0.68, p > .01), but not between either of these two variables and arterial pressure. Thus, despite equal blood pressure control, wall thickness of resistance vessels regressed more with C-D than with H, suggesting that vascular hypertrophy, like left ventricular hypertrophy, is not determined by blood pressure levels alone. Moreover, thickening of resistance vessels and increased left ventricular mass, although changing in the same direction, were related to each other to a limited degree (y2 = 0.46) both during the development of hypertension and in its response to treatment.