ASSESSMENT OF THE ANGIOTENSIN II-FORMING PATHWAY IN HUMAN ATRIA

A cardiac angiotensin II-generating system is thought to be involved i n cardiac fibrosis. Both angiotensin-converting enzyme (ACE) and human chymase can convert angiotensin I to angiotensin II. However, the rel ative contributions of these two enzymatic pathways to angiotensin II generation in vivo remain to be clarified. In 31 patients with heart d iseases, we assessed the expression levels of mRNAs for collagen type I-alpha, ACE, and chymase in right atrial appendages by competitive re verse transcriptional polymerase chain reaction and Northern blot anal yses. The expression level of the ACE mRNA was about 100 times higher than that of the chymase mRNA. The collagen type I-alpha mRNA concentr ation was significantly and positively correlated with both the mean p ulmonary arterial pressure (r = 0.414; P = 0.020) and the ACE mRNA con centration (r = 0.548; P = 0.0014). However, the chymase mRNA concentr ation was not correlated with the collagen type I-alpha mRNA concentra tion. Mutivariate 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 affec t tissue angiotensin II levels in human atria. However, we obtained no evidence that chymase is important in determining tissue angiotensin II level.