The novel serine protease PreR-Co promotes endothelium-independent vasorelaxation in rabbit aortic rings.
The effect of a novel enzyme (PreR-Co) that activates renal prorenin was studied on rabbit aortas with and without endothelium. It was tested 1) in the basal tone of nonstimulated or ANG II-sensitized rings or rings precontracted with norepinephrine (NE), PGF(2alpha), high KCl concentration, and 2) in rings pretreated with enalaprilat, losartan, PD-123319, N(omega)-nitro-l-arginine methyl ester, HOE-140, indomethacin, or serine protease inhibitors (PMSF, aprotinin, or soybean trypsin inhibitor); kallilkrein and bradykinin were also tested in ANG II-sensitized rings. PreR-Co produced a vasorelaxant effect in the basal tone and in the precontracted rabbit aorta. The effect was endothelium independent, potentiated by endothelium removal or nitric oxide (NO) synthase inhibition, and abolished by boiling the enzyme. In addition, the effect improved when basal tone was increased in ANG II-sensitized aortic rings or in precontracted vessels. No activation of the ANG II, bradykinin, prostaglandin, or NO pathway mediating the PreR-Co response could be obtained, suggesting a direct action of the enzyme. This action seems to be dependent on esterasic activity because serine protease inhibitors like PMSF and aprotinin were able to block the vasorelaxant effect of PreR-Co.
Peral De Bruno
María
M
Departamento Biomédico, Facultad de Medicina, Universidad Nacional de Tucumán, San Miguel de Tucumán 4000, Argentina. mperal@tucbbs.com.ar
Vincent
Paula A
PA
Romano
Liliana
L
Guardia
D Cecilia
DC
Coviello
Alfredo
A
De Vito
Eduardo
E
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology*; D001920:Bradykinin / Q000378:metabolism; D010450:Endopeptidases / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007610:Kallikreins / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D004791:Enzyme Inhibitors; D015842:Serine Proteinase Inhibitors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019001:Nitric Oxide Synthase; D010450:Endopeptidases; D007610:Kallikreins; C453579:PreR-Co; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester