Altered pulmonary microvascular reactivity to norepinephrine in canine pacing-induced heart failure.
Pulmonary hypertension in congestive heart failure causes medial hypertrophy in pulmonary vessels and thickening of the endothelial basement membrane. In this study, the functional consequences of such pulmonary vascular adaptations were evaluated. Heart failure was induced in dogs by rapid ventricular pacing (240 beats per minute) for 28 days, at which time left ventricular shortening fraction was decreased by 57% compared with that at baseline. Lung lobes from paced (n = 56) and control dogs (n = 68) were isolated and perfused with autologous blood. Total, arterial (Ra), and venous (Rv) vascular resistances were significantly increased and vascular capacitance decreased in lobes from paced animals compared with controls. Increments in Ra and Rv after intra-arterial boluses of norepinephrine were measured before and after sequential addition of the alpha 1- and alpha 2-receptor antagonists prazosin (16 mumol/L) and yohimbine (0.1 mumol/L) in the presence or absence of propranolol (5 mumol/L). Norepinephrine (1 to 40 micrograms) had little effect on Ra in the absence of propranolol, a pattern that persisted in control lobes after propranolol. However, when lobes from paced animals were pretreated with propranolol, norepinephrine increased Ra, Rv was increased after norepinephrine in control lobes, an effect that was enhanced in the paced group. In both groups, the increment in Rv was greater after propranolol. Irrespective of propranolol pretreatment, prazosin significantly attenuated, if not abolished, the response to norepinephrine. The enhancement in venous vascular reactivity in lobes from paced animals remained when venous pressure was elevated to 20 cm H2O. In control lobes under conditions of elevated tone or when endothelium-dependent relaxing factor was blocked, responses to norepinephrine did not mimic those observed in the paced group. Microvascular permeability, as measured by the capillary filtration coefficient, was not altered in the paced group. We conclude that the pulmonary adaptations to 4 weeks of rapid ventricular pacing include functional changes in pulmonary hemodynamics and vascular reactivity but not in microvascular permeability.
Townsley
M I
MI
Department of Physiology and Pediatrics, University of South Alabama, Mobile 36688.
Pitts
V H
VH
Ardell
J L
JL
Zhao
Z
Z
Johnson
W H
WH
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D006333:Heart Failure / Q000209:etiology* / Q000503:physiopathology*; D006439:Hemodynamics; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D009638:Norepinephrine / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D013565:Sympatholytics / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D013565:Sympatholytics; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine