Increased plasma levels of adrenomedullin in patients with pulmonary hypertension

Abstract

Adrenomedullin, a potent hypotensive peptide, reduces blood pressure and pulmonary vascular resistance, and increases pulmonary blood flow. The mRNA for adrenomedullin and its receptor is highly expressed in the lung, suggesting a regulatory role for adrenomedullin in the pulmonary circulation. To investigate the clinical significance of adrenomedullin in patients with pulmonary hypertension, we studied the relationship between plasma levels of adrenomedullin and pulmonary haemodynamics. Venous, arterial and pulmonary arterial blood samples were obtained during cardiac catheterization and plasma levels of adrenomedullin were measured by specific radioimmunoassay in 33 consecutive patients with severe pulmonary hypertension (12 cases of primary pulmonary hypertension, 21 with chronic thromboembolic pulmonary hypertension; age 49+/-16 years, mean pulmonary arterial pressure 50+/-15mmHg). In addition, plasma levels of adrenomedullin were measured before and after acute nitric oxide inhalation. The changes in plasma adrenomedullin during the follow-up period of 10.3+/-4.3 months were also evaluated (n=5). Sixty-two healthy subjects served as the control group. Adrenomedullin was measured in an antecubital vein in the controls. Plasma levels of adrenomedullin were significantly higher in the patients with pulmonary hypertension than in the control subjects (10.1+/-8.7 versus 4.9+/-1.1pmol/l, P<0.01). Plasma levels of adrenomedullin, expressed as their natural logarithm, were significantly correlated with mean right atrial pressure (r=0.71, P<0.01), stroke volume (r=-0.63, P<0.01), total pulmonary resistance (r=0.60, P<0.01), mean pulmonary arterial pressure (r=0.37, P<0.05), and the natural logarithm of plasma atrial natriuretic peptide (r=0. 63, P<0.01). Plasma levels of adrenomedullin did not change significantly after nitric oxide inhalation, but significantly increased in association with the elevation of the total pulmonary resistance during the long-term follow-up period. These results suggest that plasma levels of adrenomedullin increase in proportion to the extent of pulmonary hypertension.

Novel Regulation of Cardiac Metabolism and Homeostasis by the Adrenomedullin-Receptor Activity-Modifying Protein 2 System

“…2 AM functions as a local autocrine/paracrine mediator, 3 as well as a circulating hormone, 4 exerting natriuretic, 5 antioxidative, 6,7 and other effects. AM levels in the blood are increased in hypertension, 4,8 heart failure, 9 and myocardial infarction, 10 which suggests its involvement in cardiovascular disease. Homozygotic AM knockout (AM −/− ) mice were dead in utero because of abnormal cardiovascular development.…”

Treating pulmonary arterial hypertension: current treatments and future prospects

“…Owji and colleagues reported that there are specific receptors for adrenomedullin in the lungs [Owji et al 1995]. It has been shown that the plasma adrenomedullin concentration increases in proportion to the severity of pulmonary hypertension, and that circulating adrenomedullin is partially metabolized in the lungs [Kakishita et al 1999]. These findings suggest that adrenomedullin plays an important role in the regulation of pulmonary vascular tone.…”

Advances in the Management of Pediatric Pulmonary Hypertension

“…216,217 Nagaya and colleagues examined the acute effects of inhaled adrenomedullin in 11 adult patients with idiopathic PH, 218 and adrenomedullin was associated with an acute decrease in PAP and PVR and increase in peak oxygen consumption during exercise.…”