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Effects of angiotensin II and aldosterone on diastolic function in vivo in normal man
P B Clarkson1, N M Wheeldon, C MacLeod
1University Department of Clinical Pharmacology, Ninewells Hospital, Dundee, Scotland, U.K.
Abstract:
1. Doppler echocardiographic indices of diastolic function and systemic haemodynamics were studied in response to infusions of angiotensin II (1, 2, 5 and 10 ng min-1 kg-1), D-aldosterone (2, 4, 10 and 20 ng min-1 kg-1) and placebo [0.9% (w/v) NaCl] in ten normal male subjects. 2. Dose-related increases in systolic and diastolic blood pressure were observed with angiotensin II infusion at rates of 2 ng min-1 kg-1 and above, whereas no changes in blood pressure occurred with D-aldosterone. No changes in aortic stroke distance or heart rate were seen with either angiotensin II or aldosterone infusion. 3. Compared with placebo, angiotensin II infusion produced a dose-related prolongation of the isovolumic relaxation time [mean and 95% confidence intervals 12.0 (8.2-15.8) ms, P < 0.001] at 10 ng min-1 kg-1, and a significant reduction in the ratio between early and late transmitral flow velocity integrals at 2 ng min-1 kg-1, [-0.84 (-1.63 to -0.05), P < 0.05] and 5 ng min-1 kg-1 [-0.76 (-1.47 to -0.05), P < 0.05]. No changes in Doppler echocardiographic indices of diastolic function were observed with D-aldosterone infusion. 4. These data suggest that angiotensin II, even at a sub-pressor concentration, produces an impairment of left ventricular diastolic filling, which occurs independently of its effect on aldosterone release.