Pulmonary microvascular dysfunction develops in rodent models of HFpEF

Abstract

Pulmonary complications are common in patients with diastolic heart failure, also known as heart failure with preserved ejection fraction (HFpEF). We tested the hypothesis that pulmonary microvascular dysfunction develops in HFpEF. We employed two different rodent models of HFpEF, uninephrectomized and DOCA (UNX‐DOCA) salt treated rats as well as uninephrectomized aldosterone (UNX‐Aldo) infused mice. Left ventricle (LV) diastolic function was assessed by transthoracic echocardiography (E/A ratio and deceleration time). Microvascular vasodilator function in rats was examined in isolated small pulmonary arteries (3rd or 4th order) using wire myography, whereas pulmonary vascular resistance (PVR) was measured in isolated perfused lungs in mice. Our results showed that LV diastolic dysfunction and increased pulmonary edema formation was accompanied by a reduced acetylcholine‐induced pulmonary artery relaxation and increased PVR in UNX‐DOCA rats and UNX‐Aldo mice, respectively, when compared to corresponding controls. Responses to the direct nitric oxide donor, sodium nitroprusside were maintained and found to be similar in the magnitude in the different groups. We also found that these functional changes were accompanied by a reduced artery lumen diameter and increased wall thickness in UNX‐DOCA rats and UNX‐Aldo mice. We concluded that both functional and morphological changes develop in the pulmonary microcirculation that could contribute to pulmonary complications, such as edema formation and pulmonary artery hypertension in HFpEF.Support or Funding Information1R01AG054651‐0117SDG33680024