Hemodynamic stresses induce endothelial dysfunction and remodeling of pulmonary artery in experimental compensated heart failure

Background-We hypothesized that, in compensated heart failure (HF), hemodyn amic perturbations and their consequences exist in pulmonary artery (PA) de spite the absence of any perturbation in thoracic aorta (TA). Methods and Results-The left coronary artery was ligated in 20 male Wistar rats with compensated HF. Four months after ligation, these rats were compa red with 20 sham-operated control rats. Blood pressure, velocity, viscosity , luminal diameter, and wall tensile and shear stresses were determined in PA and TA. Arterial rings were mounted in a myograph for ex vivo study. End othelial nitric oxide synthase (eNOS) mRNA expression was determined in lun g and aorta. Sections of PA and TA were used for histomorphometric study. I n PA from rats with compensated HF, (1) blood pressure and wall tensile str ess increased, whereas blood velocity and wall shear stress decreased; (2) contractions to KCl were not altered, but maximal contraction to phenylephr ine and EC50 decreased; (3) endothelium-dependent relaxation to acetylcholi ne and basal NO activity were blunted, whereas endothelium-independent nt r elaxation was preserved; (4) eNOS mRNA levels and eNOS transcription in lun g nuclei decreased; and (5) medial cross-sectional area, thickness, smooth muscle cell number, elastin, and collagen contents increased. Conversely, n o such changes were found in TA from rats with compensated HF. Conclusions-In compensated HF induced by small myocardial infarction, hemod ynamics, vascular wall function, and structure are altered in PA but preser ved in TA. These results indicate that the pulmonary vascular bed is an ear ly target of regional circulatory alterations in HF.