A. Cadene et al., CHARACTERIZATION OF VANADYL SULFATE EFFECT ON VASCULAR CONTRACTION - ROLES OF CALCIUM AND TYROSINE PHOSPHORYLATION, The Journal of pharmacology and experimental therapeutics, 281(1), 1997, pp. 491-498
In order to explore the mechanism of action of vanadyl sulfate (VOSO4)
, previously described as an antidiabetic and antihypertensive agent,
we have investigated the role of calcium and tyrosine phosphorylation
in the contractile responses of rat aorta or skinned rabbit mesenteric
artery rings. VOSO4 induced a concentration-dependent contraction of
aorta (pD(2) = 3.2), which was potentiated by endothelium removal (pD(
2) = 4.2). After a first exposure to VOSO4, no change in responsivenes
s was observed even though high vanadium concentrations had accumulate
d in the aortic tissue (approximate to 4 x 10(-3) M). VOSO4 induced, i
n calcium-free medium, a significant response that, relative to contra
ctions measured in Krebs-Henseleit buffer, was higher (36%) than norep
inephrine (16%)-, arginine-vasopressin (8%)- or KCl (5%)-induced respo
nses. 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride
(TMB-8), an intracellular calcium release inhibitor, did not modify V
OSO4-induced response either in the presence or in the absence of ambi
ent calcium. On skinned preparations, VOSO4 antagonized Ca++-induced c
ontraction. The tyrosine kinase inhibitors tyrphostin 23 (T-23) and ty
rphostin 47 (T-47) potentiated by 4- and 14-fold, respectively, the ac
tivity of VOSO4, in contrast to the lack of effect of T-47 on pervanad
ate-induced contraction. When phosphotyrosine content was revealed by
Western blotting, VOSO4 had no effect alone, but in the presence of T-
47, it dramatically increased the phosphotyrosine content. This result
contrasts again with PV-induced tyrosine phosphorylation, which was b
locked by T-47. These data suggest that the signaling events involved
in vascular effects of VOSO4, although they depend little on calcium m
obilization, are related to tyrosine phosphorylation, likewise through
a pathway different from that of pervanadate.