Grantham J A, Borgeson D D, Burnett J C
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA.
Am J Physiol. 1997 Apr;272(4 Pt 2):R1077-83. doi: 10.1152/ajpregu.1997.272.4.R1077.
Controversy persists regarding the acute responsiveness of atrial (ANP) and brain (BNP) natriuretic peptides in pathophysiological conditions such as acute heart failure (AHF). This study was designed to test the hypothesis that AHF is characterized by selective activation of ANP, but not BNP. We also hypothesized that BNP replacement in AHF would reduce cardiac filling pressures, increase sodium excretion, and inhibit circulating renin. Two groups of anesthetized dogs underwent rapid left ventricular pacing to induce AHF. Group 1 (n = 7) served as control and group 2 (n = 7) received canine BNP (10 ng x kg(-1) x min(-1)). Cardiorenal parameters, circulating natriuretic peptides, 3',5'-cyclic guanosine monophosphate (cGMP), and plasma renin activity (PRA) were determined at baseline and during AHF in both groups. AHF was characterized by reductions in cardiac output (2.3 +/- 0.2 vs. 3.7 +/- 0.3 l/min, P < 0.05), pulmonary capillary wedge pressure (PCWP; 11.7 +/- 0.8 vs. 5.1 +/- 0.3 mmHg, P < 0.05), and selective activation of ANP (250 +/- 51 vs. 39 +/- 13 pg/ml, P < 0.05), with no increase in circulating BNP (49 +/- 15 vs. 60 +/- 16 pg/ml, P = not significant). Compared with control, exogenous supplemental BNP in AHF resulted in marked increases in circulating cGMP (65 +/- 6 vs. 18 +/- 5 pg/ml, P < 0.05), with reductions in PCWP (9.1 +/- 0.9 vs. 12.9 +/- 1.1 mmHg, P < 0.05) and increased urinary sodium excretion (120 +/- 36.8 vs. 24 +/- 6.3 microeq/min, P < 0.05) via reductions in distal tubular sodium reabsorption (94.3 +/- 1.8 vs. 98.0 +/- 0.4%, P < 0.05). Exogenous BNP prevented the increase in PRA that occurred in the control group. We conclude that AHF is characterized by a failure to increase circulating BNP underscoring differential physiological and pathophysiological roles for ANP and BNP in states of immediate cardiac overload. These studies also support a potential role for BNP in the therapeutics of AHF.
对于心房钠尿肽（ANP）和脑钠尿肽（BNP）在急性心力衰竭（AHF）等病理生理状况下的急性反应性，目前仍存在争议。本研究旨在验证以下假设：AHF的特征是ANP选择性激活，而非BNP。我们还假设，在AHF中补充BNP将降低心脏充盈压、增加钠排泄并抑制循环肾素。两组麻醉犬接受快速左心室起搏以诱导AHF。第1组（n = 7）作为对照组，第2组（n = 7）接受犬BNP（10 ng·kg⁻¹·min⁻¹）。在两组的基线期和AHF期间，测定心肾参数、循环钠尿肽、3',5'-环磷酸鸟苷（cGMP）和血浆肾素活性（PRA）。AHF的特征为心输出量降低（2.3±0.2 vs. 3.7±0.3 l/min，P<0.05）、肺毛细血管楔压（PCWP；11.7±0.8 vs. 5.1±0.3 mmHg，P<0.05）以及ANP选择性激活（250±51 vs. 39±13 pg/ml，P<0.05），而循环BNP未增加（49±15 vs. 60±16 pg/ml，P无统计学意义）。与对照组相比，AHF中外源性补充BNP导致循环cGMP显著增加（65±6 vs. 18±5 pg/ml，P<0.05），PCWP降低（9.1±0.9 vs. 12.9±1.1 mmHg，P<0.05），尿钠排泄增加（120±36.8 vs. 24±6.3 μeq/min，P<0.05），这是通过降低远端肾小管钠重吸收实现的（94.3±1.8 vs. 98.0±0.4%，P<0.05）。外源性BNP阻止了对照组中出现的PRA升高。我们得出结论，AHF的特征是循环BNP未能增加，这突出了ANP和BNP在即刻心脏超负荷状态下不同的生理和病理生理作用。这些研究还支持BNP在AHF治疗中的潜在作用。
