Hypertensive left ventricular hypertrophy(LVH) is associated with altered left ventricular (LV) filling; this may persist despite regression of LVH with treatment. Collagen occupies about 3% of the LV mass and contributes to myocardial stiffness. Collagen content may be assessed experimentally by assay of hydroxyproline, an amino acid virtually unique to collagen. The effects of lisinopril treatment on LV hydroxyproline content were studied in 15 week old spontaneously hypertensive rats (SHR) and 15 week old normotensive Wistar Kyoto rats (WKY). Rats were treated with lisinopril (LIS) in water (5mg/kg/day) for 8 weeks. Control rats were given plain tap water. LV hydroxyproline content was assayed by a spectrophotometric method after sacrifice. LIS lowered blood pressure (BP) in SHR significantly; BP in WKY was unaltered. LV mass was significantly greater in SHR controls than WKY controls (1062±40mg vs 896±9.4mg, p<0.01). LV mass regressed with LIS in both SHR (1062±40 vs 786±18.3mg, p<0.001) and WKY (896±9.4 vs 760±33.1mg, p<0.01). Hydroxyproline levels were significantly higher in treated SHR than controls: no difference was seen between treated and control WKYLV hydroxyproline (mean ± SEM)μg/g tissueμg/mg DNAμg/mg proteinSHR (control)413.0±32.0143.1±48.32.13±0.17SHR + LIS525.6±32.1*183.6±10.8*2.72±0.17*WKY (control)452.1±31.9164.4±7.22.40±0.14WKY + LIS517.8±26.9176.2±8.32.70±0.13*p<0.05 vs appropriate controlRegression of LVH in SHR with Iisinopril treatment was associated with significantly increased hydroxyproline per unit weight of tissue, protein and DNA. Selective regression of cardiac proteins with lisinopril may have important function implications