Key result
MANP plus furosemide maximizes blood pressure reduction and blunts aldosterone increases in hypertensive rats.
Why the study?
Furosemide enhances antihypertensive effectiveness but activates the renin-angiotensin-aldosterone system; whether the pGC-A activator MANP exerts cardiorenal actions, potentiates furosemide BP-lowering, and reduces aldosterone production was unknown.
Does MANP combined with furosemide reduce blood pressure and prevent furosemide-induced aldosterone increases in spontaneously hypertensive rats?
RCT (n=60)
randomized
Does MANP combined with furosemide reduce blood pressure and prevent furosemide-induced aldosterone increases in spontaneously hypertensive rats?
p-value: p=<0.05
In a hypertensive rat model, MANP potentiated the blood pressure-lowering effects of furosemide while suppressing its adverse activation of the renin-angiotensin-aldosterone system.
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·min]) and MANP600 (600 pmol/[kg·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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A 2022 study conducted an RCT in Hypertension (n=60). MANP + furosemide vs. Vehicle, MANP alone, or furosemide alone was evaluated on Blood pressure and plasma aldosterone (p=<0.05). MANP combined with furosemide produced the greatest blood pressure reduction and significantly attenuated furosemide-induced increases in plasma aldosterone in hypertensive rats (P<0.05).
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