# Evaluation of Plasma Nitric Oxide and Serum Endothelial Nitric Oxide Synthase in Pulmonary Hypertensive Dogs: A Clinical and Echocardiography Investigation

## TL;DR

This study investigates nitric oxide and endothelial nitric oxide synthase levels in dogs with pulmonary hypertension, finding higher levels that may reflect compensatory mechanisms.

## Contribution

The study is the first to evaluate NO/eNOS in dogs with PH, revealing correlations with cardiovascular changes.

## Key findings

- Dogs with PH had significantly higher plasma NO and serum eNOS levels compared to healthy dogs.
- Plasma NO was positively correlated with left ventricular hemodynamics and pulmonary distensibility but negatively with pulmonary vascular resistance.
- Dogs with PH and ascites had lower plasma NO levels and a decreasing eNOS trend.

## Abstract

Pulmonary hypertension (PH) is characterized by high pulmonary arterial pressure. Its clinical signs include collapse, weakness, and difficulty breathing. Severe PH can lead to the development of syncope and ascites associated with right-sided congestive heart failure. Nitric oxide (NO)/endothelial nitric oxide synthase (eNOS) are elemental factors in NO/cGMP signaling that regulate vascular smooth muscle tone. To date, there are no studies on NO/eNOS in dogs with PH. Thus, the present study aims to assess alterations in NO/eNOS in dogs with PH, and their correlations with cardiovascular modifications. The results show significant increases in NO/eNOS levels in the blood of dogs with PH compared with healthy dogs, suggesting compensatory responses to cardiovascular changes.

Nitric oxide (NO), an endogenous vasodilator, has been proposed as a biomarker for pulmonary hypertension (PH) in humans. NO is synthesized by endothelial nitric oxide synthase (eNOS). Alterations in NO/eNOS have not been studied in dogs with PH. We assessed alterations in NO and eNOS in the blood of dogs with PH (n = 17) and healthy dogs (n = 10) and analyzed their correlations with echocardiographic parameters. The results showed significantly higher plasma NO and serum eNOS levels in dogs with PH compared with healthy dogs. Dogs with PH and ascites (n = 11) had significantly lower plasma NO levels than those without ascites (n = 6) and presented a decreasing eNOS trend. In dogs with PH, plasma NO was positively correlated with left ventricular hemodynamics, right ventricular compliance, and pulmonary distensibility, but was negatively correlated with pulmonary vascular resistance and right cardiac remodeling. Serum eNOS was positively correlated with the main pulmonary artery diameter. Increments in NO/eNOS reflected compensatory responses to cardiovascular changes in PH. These compensations were downward in the advanced stages. Other factors may also impact NO/eNOS compensation. Although the role of NO/eNOS as biomarkers for PH in dogs remains equivocal, they may indicate compensatory consequences of cardiovascular alterations.