Secretin as an important modulator in cardiopulmonary system through renin-angiotensin-aldosterone system

Abstract

The dysregulation of the Renin-Angiotensin-Aldosterone system (RAAS) is related to idiopathic pulmonary arterial hypertension, essential systemic hypertension and myocardial apoptosis and fibrosis. Secretin (SCT) exhibits short-term stimulatory effects on the cardiovascular system, pulmonary system and central action of angiotensin II. We investigated the effect of SCT deficiency on the cardiopulmonary system, in relation to RAAS dysregulation. We demonstrated that pulmonary and systemic arterial pressures were significantly elevated in SCT-/- mice compared with the age-matched control C57BL/6N mice. Arterial wall thickening, perivascular fibrosis and edema formation and bronchiolar epithelium disruption were also observed in the lungs of SCT-/- mice. SCT-/- mice also exhibited cardiac fibrosis and increased in vivo apoptotic activity in the heart. Echocardiographic measurements correlated with high pressure in the pulmonary circulation and cardiac pathology. In accordance with high blood pressure in both the pulmonary and systemic circulation, as well as heart and lungs pathologies, increased plasma level of aldosterone and plasma aldosterone to renin ratio were observed in SCT-/- mice compared with C57BL/6N mice. Interestingly, serum nitric oxide (NO) level is significantly reduced in SCT-/- mice. After 3 months of continuous SCT infusion, pathological features in the heart and lungs were significantly attenuated in 3-6-month-old and moderately relieved in 6-9-month-old SCT-/- mice. Interestingly intraperitoneal SCT injection was also found to reduce blood pressure, and the a-week-long SCT replacement was also able to reduce the plasma aldosterone concentration in the blood and revert the aldosterone to renin ratio similar to control C57BL/6N mice levels. This study shows that SCT deficiency causes pulmonary and systemic arterial hypertension. This deficiency also contributes to pulmonary arterial wall thickening, perivascular edema and fibrosis, in the lungs, as well as apoptosis and fibrosis in the heart. These pathophysiological changes are related to the dysregulated renin angiotensin aldosterone system and are correctable after secretin replacement.