Tsutamoto T, Kanamori T, Wada A, Kinoshita M
First Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.
J Am Coll Cardiol. 1992 Sep;20(3):541-6. doi: 10.1016/0735-1097(92)90005-8.
This study was designed to evaluate the role of endogenous atrial natriuretic peptide in the pulmonary circulation in patients with chronic heart failure.
Plasma atrial natriuretic peptide concentrations in patients with heart failure have been reported to be higher than those in normal subjects and to increase as the severity of heart failure progresses. Although endogenous atrial natriuretic peptide is thought to improve the condition of patients with heart failure by reducing preload and afterload, recent findings have indicated that a high plasma atrial natriuretic peptide level is a prognostic predictor in patients with heart failure.
To evaluate the pathophysiologic role of endogenous atrial natriuretic peptide in the pulmonary circulation, plasma atrial natriuretic peptide and cyclic guanosine monophosphate (cGMP) levels were determined in the main pulmonary artery and pulmonary capillary wedge region in 80 patients with chronic congestive heart failure (New York Heart Association functional classes II to IV).
The plasma atrial natriuretic peptide level decreased significantly from the main pulmonary artery to the pulmonary capillary wedge region, whereas the plasma cGMP level increased significantly from the main pulmonary artery to the pulmonary capillary wedge region. In patients with mild chronic heart failure (n = 50), the plasma atrial natriuretic peptide level correlated with the cGMP level in the main pulmonary artery (gamma = 0.71, p less than 0.001). The atrial natriuretic peptide extraction level, calculated as (Atrial natriuretic peptide in the main pulmonary artery--Atrial natriuretic peptide in the pulmonary capillary wedge region) x Cardiac output x (1-hematocrit/100) (ng/min), also correlated with the cyclic guanosine monophosphate production level, calculated as (cGMP in the pulmonary capillary wedge region--cGMP in the main pulmonary artery) x Cardiac output x (1-hematocrit/100) (nmol/min) (gamma = 0.78, p less than 0.001). In contrast, such correlations were not found in patients with severe chronic heart failure (n = 30). In these patients, the atrial natriuretic peptide extraction level was significantly higher but there was no significant difference in the cGMP production level between the two groups (mild and severe chronic heart failure). Therefore, the molar ratio of cGMP production to atrial natriuretic peptide extraction in the pulmonary circulation was significantly lower in patients with severe chronic heart failure (88 +/- 16 vs. 480 +/- 41, p less than 0.001).
These results indicate that down-regulation of atrial natriuretic peptide receptors coupled to guanylate cyclase may occur in the pulmonary vascular beds of patients with severe chronic heart failure.
本研究旨在评估内源性心房利钠肽在慢性心力衰竭患者肺循环中的作用。
据报道，心力衰竭患者的血浆心房利钠肽浓度高于正常受试者，且随着心力衰竭严重程度的进展而升高。尽管内源性心房利钠肽被认为可通过降低前负荷和后负荷来改善心力衰竭患者的病情，但最近的研究结果表明，高血浆心房利钠肽水平是心力衰竭患者的预后预测指标。
为评估内源性心房利钠肽在肺循环中的病理生理作用，测定了80例慢性充血性心力衰竭（纽约心脏协会心功能分级II至IV级）患者主肺动脉和肺毛细血管楔压区域的血浆心房利钠肽和环磷酸鸟苷（cGMP）水平。
从主肺动脉到肺毛细血管楔压区域，血浆心房利钠肽水平显著降低，而血浆cGMP水平则显著升高。在轻度慢性心力衰竭患者（n = 50）中，血浆心房利钠肽水平与主肺动脉中的cGMP水平相关（γ = 0.71，p < 0.001）。心房利钠肽提取水平计算为（主肺动脉中的心房利钠肽 - 肺毛细血管楔压区域中的心房利钠肽）×心输出量×（1 - 血细胞比容/100）（ng/min），也与环磷酸鸟苷生成水平相关，计算为（肺毛细血管楔压区域中的cGMP - 主肺动脉中的cGMP）×心输出量×（1 - 血细胞比容/100）（nmol/min）（γ = 0.78，p < 0.001）。相比之下，在重度慢性心力衰竭患者（n = 30）中未发现此类相关性。在这些患者中，心房利钠肽提取水平显著更高，但两组（轻度和重度慢性心力衰竭）之间的cGMP生成水平无显著差异。因此，重度慢性心力衰竭患者肺循环中环磷酸鸟苷生成与心房利钠肽提取的摩尔比显著更低（88 ± 16 vs. 480 ± 41，p < 0.001）。
这些结果表明，在重度慢性心力衰竭患者的肺血管床中，可能发生与鸟苷酸环化酶偶联的心房利钠肽受体下调。
