AJP - Heart and Circulatory Physiology, Vol 271, Issue 1 222-H227, Copyright © 1996 by American Physiological Society

ARTICLES

Pulmonary vascular response to angiotensin II in canine pacing-induced heart failure

B. J. Roy, V. H. Pitts and M. I. Townsley
Department of Physiology, University of South Alabama, Mobile 36688, USA.

The effects of angiotensin II(ANG II) on pulmonary vascular resistance and microvascular permeability were studied in isolated, blood-perfused, ventilated canine lung lobes from control animals (n = 40) and animals with pacing-induced heart failure (n = 15). Conditioned dogs were paced (245 beats/min) for 30.6 +/- 0.9 (SE) days until left ventricular shortening fraction decreased by 56% (P < 0.05). Baseline pulmonary arterial resistance (Ra) (19.1 +/- 1.6 vs. 8.0 +/- 1.1 cmH2O.1(-1).min.100g) and venous resistance (Rv) (17.1 +/- 2.3 vs. 7.8 +/- 1.0 cmH2O.1(-1).min.100 g) were greater (P < 0.05) in the paced group compared with controls, respectively. Increments in Ra (delta Ra) and Rv(delta Rv) were measured after intra-arterial boluses of ANG II (1-10 micrograms). ANG II produced a dose-dependent response in delta Ra that was enhanced after pacing (P < 0.05). There was no effect on delta Rv in either group. At increased venous pressure (Pv = 20 cmH2O), the increments in delta Ra were significantly attenuated in both groups. In control lobes at low Pv, delta Ra and delta Rv both tended to decrease with increased lobar blood flow, suggesting that blood flow affects the pulmonary vascular response of ANG II. The baseline capillary filtration coefficient (Kf,c) was not different in the paced group compared with control, nor was there any effect of ANG II on Kf,c in the paced group. However, Kf,c did increase after ANG II in the control groups evaluated at either low or high Pv (P < 0.05). This difference in Kf,c was not seen if the experiment was done at increased Pv but without ANG II administration. We conclude that the pulmonary vasoconstrictor activity of ANG II is modestly enhanced in canine pacing-induced heart failure. Nonetheless, ANG II does not likely contribute to increased pulmonary vascular resistance in vivo in heart failure, since this effect was abolished at increased Pv. Finally, the absence of any effect of ANG II on pulmonary microvascular permeability in the paced group is suggestive of some adaptive remodeling of the capillary endothelial barrier.

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