DISCREPANCY BETWEEN PLASMA AND AORTIC-WALL CYCLIC GUANOSINE-MONOPHOSPHATE IN AN EXPERIMENTAL-MODEL OF CONGESTIVE-HEART-FAILURE

被引:9
作者
ARNAL, JF [1 ]
HOFMANN, F [1 ]
MICHEL, JB [1 ]
机构
[1] TECH UNIV MUNICH,INST PHARMACOL & TOXICOL,W-8000 MUNICH 40,GERMANY
关键词
ATRIAL NATRIURETIC PEPTIDE; ENDOTHELIUM DERIVED RELAXING FACTOR; CYCLIC GUANOSINE MONOPHOSPHATE; CONGESTIVE HEART FAILURE;
D O I
10.1093/cvr/27.6.1094
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives: The state of the vasodilator systems in congestive heart failure is poorly defined. Plasma atrial natriuretic peptide is increased, whereas endothelium derived relaxing factor activity can be decreased. Atrial natriuretic peptide and endothelium derived relaxing factor both cause vascular relaxation by generating cyclic guanosine monophosphate (cGMP), by activating the particulate and the soluble guanylate cyclase, respectively. This study examines the biological effects of atrial natriuretic peptide and endothelium derived relaxing factor in experimental heart failure by assessing the plasma, urinary, and tissue concentrations of their common second messenger cGMP. Methods: Myocardial infarctions (n=31) were induced and sham operations (n=25) were performed on Wistar rats, and the rats were monitored for three months. Aortic and pulmonary cGMP contents were measured, as the aorta is mainly matrix and smooth muscle cells, and the lung is particularly rich in capillaries, hence in endothelial cells. The concentrations of the other second messenger cyclic adenosine monophosphate (cAMP) was also determined, as were those of cGMP dependent protein kinase in the arteries. Results: 17 of the 31 rats with myocardial infarction had oedema. The total heart weight to body weight ratio and the ratio of the myocardium haemodynamically upstream from the infarcted left ventricle to body weight were increased in proportion to the infarct size. Plasma atrial natriuretic peptide and plasma and urinary cGMP concentrations were increased in proportion to the degree of heart failure (p<0.0001). The pulmonary cGMP concentration was significantly higher in the rats with myocardial infarction than in the control group (p<0.0001). Pulmonary cGMP concentrations were correlated with the plasma concentrations of atrial natriuretic peptide and cGMP (r 2=0 .59 and 0.66 respectively, p<0.0001). The cGMP, cAMP, and cGMP, and cGMP dependent kinase concentrations in the aortic wall of rats with myocardial infarctions were the same as in control rats. Conclusions: The increase in plasma, urinary, and pulmonary cGMP in rats with myocardial infarctions were highly correlated with the increase in circulating atrial natriuretic peptide. By contrast, the aortic cGMP concentration was unchanged in these rats, despite high plasma atrial natriuretic peptide. In congestive heart failure, a discrepancy seems to exist between pulmonary (mainly endothelium) and aortic wall (mainly smooth muscle cells) cGMP.
引用
收藏
页码:1094 / 1100
页数:7
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