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December 1, 1996Circulation68 citations

Equipotent Antihypertensive Agents Variously Affect Pulsatile Hemodynamics and Regression of Cardiac Hypertrophy in Spontaneously Hypertensive Rats

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GMGary F. MitchellMPMarc A. PfefferPFPeter Finn

Key Result

Zofenopril reduced the ratio of left ventricular weight to body weight more effectively than hydralazine (2.4 vs 3.3 g/kg, P<0.005) in spontaneously hypertensive rats.

Structured PICO

Does zofenopril or hydralazine improve pulsatile hemodynamics and regress left ventricular hypertrophy in spontaneously hypertensive rats?

P
Population
18-month-old male spontaneously hypertensive rats (SHR)
I
Intervention
Zofenopril or hydralazine for 6 months
C
Comparator
Water for 6 months
O
Outcome
Pulsatile hemodynamics and regression of left ventricular hypertrophy (ratio of left ventricular weight to body weight)surrogate

In spontaneously hypertensive rats, zofenopril is more effective than hydralazine at regressing left ventricular hypertrophy due to a greater reduction in total left ventricular load and pulsatile load.

Main Result

Absolute Event Rate: 2.4% vs 3.9%

p-value: p=<.005

Abstract

BACKGROUND: Converting enzyme inhibitors are more effective than arteriolar vasodilators at regressing left ventricular hypertrophy in spontaneously hypertensive rats (SHR), possibly because of nonhemodynamic factors. However, the pulsatile component of hemodynamic load has not been evaluated in this model. METHODS AND RESULTS: We measured pulsatile hemodynamics in 18-month-old male SHR after 6 months of therapy with either zofenopril (Z), hydralazine (H), or water (W). Hydralazine and zofenopril reduced mean arterial pressure comparably (W, 106 +/- 23 versus H, 81 +/- 12 versus Z, 84 +/- 18 mm Hg, P = .002) yet had a differential effect on the ratio of left ventricular weight to body weight (W, 3.9 +/- 0.5 versus H, 3.3 +/- 0.4 versus Z, 2.4 +/- 0.2 g/kg, P < .005). Hydralazine-treated SHR had increased characteristic impedance (P = .0011) and a persistently low ratio of the reflected-wave transit time to left ventricular ejection time (P < .001), which contributed to early and late systolic loading, respectively, of the left ventricle. Consequently, only zofenopril-treated SHR had a significant reduction in left ventricular systolic force-time integral (P = .02), a measure of total ventricular load. There were no differences in systolic stress-time integral, suggesting that mass was appropriate to load when all elements of steady-flow and pulsatile load were considered. CONCLUSIONS: A blunted reduction in total left ventricular load, due to increased pulsatile load in SHR treated with hydralazine, provided a hemodynamic basis for the differential regression of hypertrophy in this model of genetic hypertension.

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Cite This Study

Mitchell et al. (1996) studied Hypertension (Spontaneously Hypertensive Rats). Zofenopril or Hydralazine vs. Water was evaluated on Ratio of left ventricular weight to body weight (p=<.005). Zofenopril reduced the ratio of left ventricular weight to body weight more effectively than hydralazine (2.4 vs 3.3 g/kg, P<0.005) in spontaneously hypertensive rats.

synapsesocial.com/papers/6a07b4da44ff8ad339f69c4ahttps://doi.org/10.1161/01.cir.94.11.2923
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