Heart Hormone Seen to Control Lung Blood Pressure, Impacting PAH, via Endothelial Cells

The cardiac hormone known as atrial natriuretic peptide (ANP) controls blood pressure both throughout the body and in the lungs. Researchers previously believed that ANP’s hypotensive effect in the lungs was mediated by changes in the smooth muscle that lines pulmonary blood vessels. But scientists now report that the hormone facilitates low blood pressure via the endothelial cells lining the blood vessels.

The study, “Endothelial actions of atrial natriuretic peptide prevent pulmonary hypertension in mice,“ was recently published in the journal Basic Research in Cardiology.

Researchers at Julius Maximilian University of Würzburg, Germany, investigated the effect of ANP by deleting the hormone’s receptor only in lung endothelial cells of mice. These mice developed pulmonary hypertension without being exposed to any other stimuli, triggering high blood pressure. The animals also had more smooth muscle around their blood vessels — a hallmark of pulmonary hypertension. The team also observed that inflammatory cells had moved into the vessel wall from the bloodstream.

When the researchers placed the mutant mice in a low oxygen environment for three weeks, they found that lung hypertension worsened. (Exposing lab animals to low oxygen is a common approach for creating live models of pulmonary hypertension.)

In studying human and mice endothelial cells in culture, the team also found expression of the ANP receptor reduced in cells exposed to hypoxia, confirming that the hypertension was likely mediated by changes in ANP signaling in these cells.

The researchers then attempted to determine the mechanism behind these changes. The ANP signaling pathway involves downstream effects on endothelin-1 and angiotensin II. These hormones are believed to contribute to the development of pulmonary hypertension, and endothelin-1 levels are known to be high in pulmonary hypertension patients. In this study, however, researchers did not see any impact on endothelin levels.

In contrast, they noted that angiotensin II levels were high. The team treated the mice with a drug that blocked angiotensin II, and found it could prevent the changes induced by low oxygen exposure.

Study results showed that endothelial cells are likely the main cell type expressing ANP receptors in the lung, and that angiotensin signaling contributes to changes in lung blood vessels that promote hypertension.