T. Kubo et al., EVIDENCE THAT ANGIOTENSIN-II, ENDOTHELINS AND NITRIC-OXIDE REGULATE MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVITY IN RAT AORTA, European journal of pharmacology, 347(2-3), 1998, pp. 337-346
We measured the activity of mitogen-activated protein (MAP) kinases, e
nzymes believed to be involved in the pathway for cell proliferation,
in rat aortic strips with or without endothelium, and examined effects
of angiotensin receptor antagonists, endothelin receptor antagonists
and nitric oxide (NO)-related agents. Endothelium removal produced an
activation of MAP kinase activity in the strips, whereas the enzyme ac
tivity was not affected in the adventitia. The MAP kinase activation w
as inhibited by either the angiotensin AT(1) receptor antagonist losar
tan or the endothelin ETA receptor antagonist BQ 123. The combination
of both antagonists caused an additive inhibition. The angiotensin AT(
2) receptor antagonist PD 123,319 and the endothelin ETB receptor anta
gonist BQ 788 did not affect the MAP kinase activation. The NO synthas
e inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) caused an activ
ation of MAP kinase in the endothelium-intact aorta and the MAP kinase
activation was inhibited by losartan or BQ123. The NO releaser nitrop
russide inhibited the MAP kinase activation induced by endothelium rem
oval or angiotensin II. These results suggest that even in isolated ar
teries, NO of endothelial origin tonically exert MAP kinase-inhibiting
effects and endogenous angiotensin II and endothelins in the media ar
e tonically released to cause MAP kinase-stimulating effects in medial
smooth muscle. (C) 1998 Elsevier Science B.V.