4.7 Article

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

Journal

HYPERTENSION
Volume 79, Issue 4, Pages 750-760

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.121.18837

Keywords

aldosterone; blood pressure; cyclic GMP; furosemide; heart failure; natriuretic peptides

Funding

  1. National Institutes of Health [RO1 HL136340]
  2. Mayo Foundation

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In this study, the researchers investigated the cardiorenal and neurohumoral actions of MANP in a genetic model of hypertension in rats. They found that MANP potentiated the blood pressure-lowering effects of furosemide, inhibited the renin-angiotensin-aldosterone system, and preserved renal function. These findings are highly relevant to the clinical treatment of hypertension and heart failure.
Background: 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. Methods: 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. Results: BP was reduced in MANP300 (300 pmol/[kg center dot min]) and MANP600 (600 pmol/[kg center dot min]) groups (P<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 (P<0.05) with no significant differences between furosemide and furosemide+MANP. In vitro, MANP increased cyclic guanosine monophosphate level in human vascular cells. Conclusions: 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.

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