Role of Elastase-2 as an Angiotensin II-Forming Enzyme in Rat Carotid Artery

Authors:
  • DSDisney O Sivieri
    Disney O Sivieri
  • MMMilene K Moysés
    Milene K Moysés
  • EOEduardo B Oliveira
    Eduardo B Oliveira
  • MSMaria Cristina O Salgado
    Maria Cristina O Salgado
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Abstract
We have described the biochemical, enzymatic, and structural properties of a chymostatin-sensitive angiotensin (Ang) I-converting elastase-2 found in the rat mesenteric arterial bed perfusate. We determined the mRNA for elastase-2 and its relative role in generating Ang II in the rat isolated aorta and carotid artery rings. In carotid rings, the Ang I-induced vasoconstrictor effect was only partially inhibited by captopril or chymostatin, whereas that of tetradecapeptide renin substrate (TDP) was greatly inhibited by chymostatin but unaffected by captopril; however, Ang I- and TDP-induced effects were abolished by the combination of both inhibitors. Effects of [Pro11-D-Ala12]-Ang I (PDA), an Ang I-converting enzyme (ACE)-resistant biologically inactive precursor of Ang II were blocked by chymostatin or N-acetyl-Ala-Ala-Pro-Leu-chloromethylketone (elastase-2 inhibitor) in carotid artery. PDA failed to induce an effect in aortic rings, and Ang I-induced contractions were completely inhibited by captopril. The mRNA for rat elastase-2 was detected in aorta, carotid, and mesenteric arteries, although its expression was found to be less important in aorta. These findings indicate the presence of a functional alternative pathway to ACE for Ang II generation in rat carotid artery and represent strong evidence of a physiological role for elastase-2; however, its functional contribution to Ang II formation in aorta appears to be negligible.
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