MANP (M-Atrial Natriuretic Peptide) Reduces Blood Pressure and Furosemide-Induced Increase in Aldosterone in Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 79; no. 4; pp. 750 - 760
• Main Authors: Dzhoyashvili, Nina A., Iyer, Seethalakshmi R., Chen, Horng H., Burnett, John C.
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins 01.04.2022
• Subjects: Aldosterone; Animals; Atrial Natriuretic Factor - pharmacology; Blood Pressure; Cyclic GMP; Furosemide - adverse effects; Guanosine Monophosphate - adverse effects; Hypertension - chemically induced; Hypertension - drug therapy; Natriuresis; Rats; furosemide; blood pressure; heart failure; natriuretic peptides; aldosterone; cyclic GMP
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.121.18837

cGMP MANP (M-atrial natriuretic peptide) is a best-in-class activator of the pGC-A (particulate guanylyl cyclase A) receptor. Furosemide increases the effectiveness of antihypertensive agents, but activates renin-angiotensin-aldosterone system. We aimed to investigate for the first time cardiorenal and neurohumoral actions of MANP in a genetic model of hypertension in spontaneously hypertensive rats. We also assessed how MANP would potentiate the blood pressure (BP)-lowering actions of furosemide while reducing the production of aldosterone. Spontaneously hypertensive rats (N=60) were randomized in vehicle, MANP, furosemide, or MANP+furosemide groups. Furosemide (1, 5, 10 mg/kg) was given as a single bolus which in MANP+furosemide groups was followed by a 60-minute infusion of MANP. BP was reduced in MANP300 (300 pmol/[kg·min]) and MANP600 (600 pmol/[kg·min]) groups ( <0.05) and was accompanied by significant increase in plasma cyclic guanosine monophosphate. Furosemide alone reduced BP but less compared with MANP with no change in plasma cyclic guanosine monophosphate. MANP+furosemide resulted in the greatest BP reduction and significant increase in plasma cyclic guanosine monophosphate in Fs5+MANP300, Fs10+MANP300, and Fs10+MANP600. Plasma aldosterone increased in furosemide groups, which was significantly attenuated in MANP+furosemide groups. Natriuresis and diuresis increased in all treated groups ( <0.05) with no significant differences between furosemide and furosemide+MANP. In vitro, MANP increased cyclic guanosine monophosphate level in human vascular cells. We provide novel evidence that MANP potentiates the BP-lowering actions of furosemide, suppresses the activation of renin-angiotensin-aldosterone system, and preserves renal function. These data are highly relevant to clinical needs in the treatment of hypertension and heart failure.