Pulmonary Vasoconstriction and Vascular Remodeling Play Role in Reactive Pulmonary Hypertension in Rats

Abstract

IntroductionThe majority of clinical cases of pulmonary hypertension (PH) are caused by left heart failure. Some patients with venous PH induced by left heart pressure overload develop increase in resistance in the arterial part of the pulmonary circulation (reactive PH). We developed a new animal model of reactive PH caused by left heart pressure overload. We tested hypothesis that pulmonary arterial vasoconstriction and/or pulmonary vascular remodeling play role in our rodent model of reactive PH.MethodsLeft heart pressure overload was induced in adult male Wistar rats by partial intravascular obstruction of the ascending aorta. Three weeks later the experimental rats (group E, n=6) were compared to controls (group C, n=7). In isolated lungs perfused with salt solution with albumin we studied hemodynamic changes in pulmonary circulation by analysis of perfusion pressure increments induced by increasing perfusion flow (P/Q relationship). The P/Q relationship measurement was repeated after adding sodium nitroprusside into perfusate to reveal presence of pulmonary arterial vasoconstriction. In lung histology we counted remodeled peripheral pulmonary vessels in the group E compared to controls.ResultsThe slope of the P/Q relationship was significantly increased in the group E compared to controls (0.112±0.003 mmHg.mL−1.min−1 vs. 0.0046±0.002 mmHg.mL−1.min−1; p<0.0001). Sodium nitroprusside did not alter the slope in controls (0.043±0.002 mmHg.mL−1.min−1). In the group E, sodium nitroprusside reduced the slope to a value not different from that in controls (0.044±0.001 mmHg.mL−1.min−1). In lung histology, 74 % of the small pulmonary vessels had muscularized media in the group E, compared to only 24 % in controls (p<0.01).ConclusionPulmonary vasoconstriction and pulmonary vascular remodeling are involved in the new model of reactive pulmonary hypertension in rats.Support or Funding InformationGrants: GAUK 210216 and GACR 17‐11223SThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.