Submitted on March 13, 2003
Accepted on July 30, 2003
ANGIOTENSIN-CONVERTING ENZYME ACTIVITY IN OVINE BRONCHIAL VASCULATURE
Aigul Moldobaeva1 and Elizabeth M Wagner1*
1 Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
* To whom correspondence should be addressed. E-mail: wagnerem{at}jhmi.edu.
Angiotensin-converting enzyme (ACE) plays a major role in the metabolism of bradykinin, angiotensin, and neuropeptides, all of which are implicated in inflammatory airways diseases. The activity of ACE, which is localized on the luminal surface of endothelial cells (EC), has been well documented in pulmonary EC, however little data exists regarding the relative activity of ACE in the airway vasculature. Therefore, we measured ACE activity in cultured EC from the sheep bronchial artery (ba), and bronchial mucosa (microvascular) and compared it to pulmonary artery (pa) EC. The baseline level of total ACE activity (cellular plus secreted) was significantly greater in bronchial microvascular EC (1.24± 0.24 mUnits/106cells) compared to bronchial artery EC (0.59± 0.15 mUnits/106cells; p<0.05) and comparable to pulmonary artery EC (1.12±0.14 mUnits/106cells; p>0.05). Measured ACE activity secreted into culture medium for each cell type was 64-74% of total activity and did not differ among the three endothelial cell types (p=0.17). Hydrocortisone (10 mg/ml; 48-72 hrs) treatment resulted in a significant increase in ACE activity in bronchial endothelial cells. Likewise, TNF-
(0.1 ng/ml) treatment markedly increased ACE activity in all cell lysates (p<0.05). We confirmed the importance of ACE activity in vivo by measuring bradykinin-induced bronchial vascular resistance before and after ACE inhibition with captopril. At the highest dose of bradykinin studied ( 10-8 M), bronchial artery pressure at constant flow showed a significantly greater bradykinin-induced dilation after captopril treatment (36% vs 60% decrease; p=0.05). Overall these results demonstrate the high level of ACE activity in the bronchial microvasculature relative to pulmonary vessels that are known to express high ACE activity, and suggest the ability of the airway vasculature to regulate ACE activity when exposed to an inflammatory cytokine. Our observations suggest an important regulatory role for ACE in the metabolism of kinin peptides known to contribute to airway pathology.
