Assessment of the angiotensin II-forming pathway in human atria

A cardiac angiotensin II-generating system is thought to be involved in cardiac fibrosis. Both angiotensin-converting enzyme (ACE) and human chymase can convert angiotensin I to angiotensin II. However, the relative contributions of these two enzymatic pathways to angiotensin II generation in vivo remain to be clarified. In 31 patients with heart diseases, we assessed the expression levels of mRNAs for collagen type I-alpha, ACE, and chymase in right atrial appendages by competitive reverse transcriptional polymerase chain reaction and Northern blot analyses. The expression level of the ACE mRNA was about 100 times higher than that of the chymase mRNA. The collagen type I-alpha mRNA concentration was significantly and positively correlated with both the mean pulmonary arterial pressure (r = 0.414; P = 0.020) and the ACE mRNA concentration (r = 0.548; P = 0.0014). However, the chymase mRNA concentration was not correlated with the collagen type I-alpha mRNA concentration. Multivariate regression analysis revealed that the collagen type I-alpha mRNA concentration was related to the ACE mRNA concentration (P = 0.0028) and to the mean pulmonary arterial pressure (P = 0.0386) [r = 0.633, P < 0.0008]. The present results suggest that ACE may affect tissue angiotensin II levels in human atria. However, we obtained no evidence that chymase is important in determining tissue angiotensin II level.