Apc. Davel et al., Effects of ouabain on the presser response to phenylephrine and on the sodium pump activity in diabetic rats, EUR J PHARM, 406(3), 2000, pp. 419-427
The diabetes mellitus insulin-dependent is usually associated with cardiova
scular disorders and with changes in the activity of the Na+,K+-ATPase. The
effects of ouabain, a Na+,K+-ATPase inhibitor, on the presser response of
7-day streptozotocin-induced diabetes were investigated in anesthetized rat
s and on the vascular reactivity of the perfused rat tail vascular bed. Dia
betes was characterized by hyperglycemia (86 +/- 7.8 vs. 471 +/- 18.5 mg/dl
) without changes in arterial blood pressure. Blood pressure increased afte
r the treatment with 18 mug/kg ouabain in controls bur not in diabetic rats
; acute hyperglycemia, in non-treated rats, did not change these effects. C
ontrol tail vascular beds showed increased maximal response to phenylephrin
e after treatment with 10 nM ouabain for 1 h; this response was abolished i
n streptozotocin-treated rats. These rats showed an increased sensitivity t
o phenylephrine without changing the maximal vasoconstrictor response when
compared to control rats. The relaxation induced by acetylcholine was reduc
ed in diabetic rats. The functional activity of the Na+,K+-ATPase was inhib
ited in vascular beds from diabetic rats, when compared to control rats, an
d the inhibition of the Na+,K+-ATPase with 10 nM ouabain was not effective
in these rats. Results suggested that in 7-day diabetic rats, the increase
of arterial blood pressure or the sensitization of the vascular bed produce
d by ouabain is lost as a consequence of the reduction of the functional ac
tivity of the Na+,K+-ATPase probably as a result of insulin lack and a defi
cient endothelial nitric oxide activity. (C) 2000 Elsevier Science B.V. All
rights reserved.