MANP (M-Atrial Natriuretic Peptide) Reduces Blood Pressure and Furosemide-Induced Increase in Aldosterone in Hypertension.
MANP (M-Atrial Natriuretic Peptide) Reduces Blood Pressure and Furosemide-Induced Increase in Aldosterone in Hypertension.
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DOI：
10.1161/hypertensionaha.121.18837
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Burnett JC Jr
中科院分区：
文献类型：
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作者：
Dzhoyashvili NA;Iyer SR;Chen HH;Burnett JC Jr
M-心房钠尿肽（MANP）是一类最好的颗粒鸟苷酸环化酶A（pGC-A）受体激活剂。呋塞米（Fs）可增强降压药的疗效，但可激活肾素-血管紧张素-醛固酮系统（RAAS）。我们的目的是调查的第一次心肾和神经体液作用的Manp在遗传性高血压模型在自发性高血压大鼠（SHR）。我们还评估了MANP如何增强FS的降压作用，同时减少醛固酮的产生。SHR（N=60）随机分为溶媒组、Manp组、Fs组和Manp+Fs组。Fs（1、5、10 mg/kg）单次静脉推注，MANP+Fs组在此基础上持续静脉输注MANP 60 min。MANP 300（300 pmol/kg/min）和MANP 600（600 pmol/kg/min）组血压降低（p<0.05），血浆环磷酸鸟苷（cGMP）显著升高。单用FS降低血压，但低于MANP，血浆cGMP无变化。在Fs 5 + MANP 300、Fs 10 + MANP 300和Fs 10 + MANP 600中，MANP+Fs导致最大的血压下降和血浆cGMP的显著增加。Fs组血浆醛固酮升高，MANP+Fs组明显降低。所有治疗组的尿钠和利尿均增加（p<0.05），Fs和Fs+Manp之间无显著差异。在体外，Manp增加人血管细胞cGMP水平。我们提供了新的证据表明，MANP增强FS的降压作用，抑制RAAS的激活，并保留肾功能。这些数据与高血压和心力衰竭治疗的临床需求高度相关。
M-atrial natriuretic peptide (MANP) is a best-in-class activator of the particulate guanylyl cyclase A (pGC-A) receptor. Furosemide (Fs) increases the effectiveness of antihypertensive agents, but activates renin-angiotensin-aldosterone system (RAAS). We aimed to investigate for the first time cardiorenal and neurohumoral actions of MANP in a genetic model of hypertension in spontaneously hypertensive rats (SHR). We also assessed how MANP would potentiate the blood pressure (BP)– lowering actions of Fs while reducing the production of aldosterone. SHR (N=60) were randomized in vehicle, MANP, Fs or MANP+Fs groups. Fs (1, 5, 10 mg/kg) was given as a single bolus which in MANP+Fs 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 (p<0.05) and was accompanied by significant increase in plasma cyclic guanosine monophosphate (cGMP). Fs alone reduced BP but less compared with MANP with no change in plasma cGMP. MANP+Fs resulted in the greatest BP reduction and significant increase in plasma cGMP in Fs5+MANP300, Fs10+MANP300 and Fs10+MANP600. Plasma aldosterone increased in Fs groups, which was significantly attenuated in MANP+Fs groups. Natriuresis and diuresis increased in all treated groups (p<0.05) with no significant differences between Fs and Fs+MANP. In vitro, MANP increased cGMP level in human vascular cells. We provide novel evidence that MANP potentiates the BP lowering actions of Fs, suppresses the activation of RAAS and preserves renal function. These data are highly relevant to clinical needs in the treatment of hypertension and heart failure.