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

by Aung Moe Zaw

Institution: University of Hong Kong
Year: 2017
Keywords: Renin-angiotensin system; Secretin; Cardiopulmonary system
Posted: 02/01/2018
Record ID: 2155136
Full text PDF: http://hdl.handle.net/10722/239938


The dysregulation of theRenin-Angiotensin-Aldosterone system (RAAS) is related toidiopathic pulmonary arterial hypertension, essential systemichypertension and myocardial apoptosis and fibrosis. Secretin (SCT)exhibits short-term stimulatory effects on the cardiovascularsystem, pulmonary system and central action of angiotensin II. Weinvestigated the effect of SCT deficiency on the cardiopulmonarysystem, in relation to RAAS dysregulation. We demonstrated thatpulmonary and systemic arterial pressures were significantlyelevated in SCT-/- mice compared with the age-matched controlC57BL/6N mice. Arterial wall thickening, perivascular fibrosis andedema formation and bronchiolar epithelium disruption were alsoobserved in the lungs of SCT-/- mice. SCT-/- mice also exhibitedcardiac fibrosis and increased in vivo apoptotic activity in theheart. Echocardiographic measurements correlated with high pressurein the pulmonary circulation and cardiac pathology. In accordancewith high blood pressure in both the pulmonary and systemiccirculation, as well as heart and lungs pathologies, increasedplasma level of aldosterone and plasma aldosterone to renin ratiowere observed in SCT-/- mice compared with C57BL/6N mice.Interestingly, serum nitric oxide (NO) level is significantlyreduced in SCT-/- mice. After 3 months of continuous SCT infusion,pathological features in the heart and lungs were significantlyattenuated in 3-6-month-old and moderately relieved in6-9-month-old SCT-/- mice. Interestingly intraperitoneal SCTinjection was also found to reduce blood pressure, and thea-week-long SCT replacement was also able to reduce the plasmaaldosterone concentration in the blood and revert the aldosteroneto renin ratio similar to control C57BL/6N mice levels. This studyshows that SCT deficiency causes pulmonary and systemic arterialhypertension. This deficiency also contributes to pulmonaryarterial wall thickening, perivascular edema and fibrosis, in thelungs, as well as apoptosis and fibrosis in the heart. Thesepathophysiological changes are related to the dysregulated reninangiotensin aldosterone system and are correctable after secretinreplacement. published_or_final_version Biological Sciences Doctoral Doctor of Philosophy