Vol. 284, Issue 2, H704-H710, February 2003
The novel serine protease PreR-Co promotes endothelium-independent vasorelaxation in rabbit aortic rings
María
Peral de
Bruno1,
Paula A.
Vincent2,
Liliana
Romano1,
D. Cecilia
Guardia2,
Alfredo
Coviello2, and
Eduardo
De
Vito2
1 Departamento Biomédico, Facultad de
Medicina, and 2 Instituto Superior de
Investigaciones Biológicas, Consejo Nacional de Investigaciones
Científicas y Técnicas, Universidad Nacional de
Tucumán, San Miguel de Tucumán 4000, Argentina
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), PGF2
, high KCl
concentration, and 2) in rings pretreated with enalaprilat, losartan, PD-123319,
N
-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.
renin activators; vasorelaxant activity; rabbit aorta
