Increased systolic performance with diastolic dysfunction in adult spontaneously hypertensive rats

Abstract

Hypertensive heart disease is characterized by early development of hypertrophy and fibrosis that leads to heart failure (HF). HF develops in spontaneously hypertensive rats (SHR) after 18 months; however, it is not clear whether hypertrophy leads to altered cardiac performance at an earlier age in these rats. We studied cardiac performance in 10- to 11-month-old SHR and age-matched Wistar-Kyoto rats (WKY), using presssure-volume (PV) conductance catheter system to evaluate systolic and diastolic function in vivo at different preloads, including preload recruitable stroke work (PRSW), +dP/dt, and its relation to end-diastolic volume (+dP/dt-EDV) and preload-adjusted maximal power (PWRmax-EDV2) as well as the time constant of left ventricular pressure decay, tau (τ), as an index of relaxation. The slope of the end-diastolic pressure-volume relation (EDPVR) and the ex vivo PV relation, both indexes of stiffness, were also calculated for each heart, and the Doppler E/A ratio was determined. In addition, plasma samples were obtained to assess B-type natriuretic peptide levels (BNP). We found that PRSW was higher in SHR than in WKY (174.5±15.6 versus 92.6±18.9 mm Hg; P<0.01). +dP/dt and +dP/dt-EDV were also enhanced in SHR versus WKY (9125±662 versus 6633±392 mm Hg/sec, P<0.01, and 28.14±4.35 versus 12.7±2.8 mm Hg/s per μL, P<0.02). In addition, PWR-EDV2 was elevated in SHR (7.3±1.5 versus 3.1±0.6 mW/μL2). τ was prolonged in SHR (14.5±1 ms versus 10.8±0.8 for WKY, P<0.02) and EDPVR was significantly greater in SHR than in WKY (0.01±0.005 versus 0.004±0.001, P<0.05). The ex vivo pressure-volume relation was also steeper for SHR and the E/A ratio was 2.53±0.15 for SHR versus 1.67±0.08 for WKY (P<0.02). BNP was 45±2.5 pg/mL for SHR and 33.3±1.8 pg/mL for WKY (P<0.02). Taken together, these data suggest that at 10 to 11 months of age, before HF develops, SHR have increased systolic performance accompanied by delayed relaxation and increased diastolic stiffness.