Differential Role of Nitric Oxide in the Modulation of Systemic and Pulmonary Pressure

Abstract

The importance of endogenous NO in the modulation of systemic circulation is well established, but its role in the pulmonary circulation remains unclear. The present study was to investigate the effects of both acute and chronic L‐NAME inhibition of NO production on aortic and pulmonary vasoreactivity. An acute bolus injection of 10 mg/kg L‐NAME resulted in a sustained increase in rat systemic pressure, while the pulmonary pressure remained unaffected. After a bolus injection of 2 μg/kg phenylephrine (PE), a marked transient increase was noted in the systemic, but not pulmonary, arterial pressure. However, in the presence of L‐NAME, similar PE challenge resulted in a marked increase in pulmonary arterial pressure, suggesting that NO release was important counteracting PE‐induced pulmonary constriction. 3 weeks chronic treatment with L‐NAME led to significant systemic hypertension without any effect on pulmonary. But with L‐NAME pretreatment, the development of monocrotaline‐induced pulmonary hypertension was significantly accelerated as compared to control group. These findings demonstrated the differential role of NO in the modulation of systemic and pulmonary circulation. In particular, NO release plays a major role maintaining the basal vascular tone in aortic but not pulmonary arteries. However, its release is obligatory in opposing pulmonary constriction and preventing pulmonary hypertension.