Article ID Journal Published Year Pages File Type
2574867 Vascular Pharmacology 2007 11 Pages PDF
Abstract

The endothelin (ET) peptides are more potent in contracting veins than arteries. The precursor big ET-1 is metabolized by endothelin converting enzyme [ECE; to ET-1 (1–21)], matrix metalloproteases [MMPs; to ET-1 (1–32)] and chymase [to ET-1(1–31)]. We hypothesized that arteries and veins were differently dependent in conversion of big ET-1 to vasoconstrictors. Immunohistochemical, western, zymographic and isometric contractile assays in rat aorta and vena cava were used. Big ET-1 contracted aorta [60 ± 17% phenylephrine contraction] but was more efficacious in vena cava [478 ± 61% norepinephrine contraction]. ECE and its product ET-1(1–21) were detected in aorta and vena cava, and the ECE inhibitors phosphoramidon and CGS-26393 reduced big ET-1-induced contraction. ET-1 (1–32) contracted aorta and vena cava but inhibition of MMPs with minocycline or GM6001 did not reduce big ET-1-induced contraction; zymography confirmed active tissue MMPs. Aorta and vena cava contracted to the product of chymase, ET-1 (1–31). Chymase was detected in aorta and only weakly in vena cava. Inhibition of chymase (chymostatin, 100 μM) reduced arterial (19% control) but not venous constriction to big ET-1. These results suggest at least one potential significant difference — the role of chymase — in in vitro enzymatic processing of big ET-1 in arteries and veins.

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