Big ET-1 processing into vasoactive peptides in arteries and veins

The endothelin (ET) peptides are more potent in contracting veins than arteries. The precursor big ET-I 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. Inummohistochemical, western, zymographic and isometric contractile assays in rat aorta and vena cava were used. Big ET-I 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 NWPs with minocycline or GM6001 did not reduce big ET-1-induced contraction; zymography confirmed active tissue NIMPs. 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 mu M) 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. (c) 2007 Elsevier Inc. All fights reserved.