Effects of ouabain on the presser response to phenylephrine and on the sodium pump activity in diabetic rats

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.