Effects of ouabain on the pressor response to phenylephrine and on the sodium pump activity in diabetic rats.
The diabetes mellitus insulin-dependent is usually associated with cardiovascular disorders and with changes in the activity of the Na(+),K(+)-ATPase. The effects of ouabain, a Na(+),K(+)-ATPase inhibitor, on the pressor response of 7-day streptozotocin-induced diabetes were investigated in anesthetized rats and on the vascular reactivity of the perfused rat tail vascular bed. Diabetes was characterized by hyperglycemia (86+/-7.8 vs. 471+/-18.5 mg/dl) without changes in arterial blood pressure. Blood pressure increased after the treatment with 18 microg/kg ouabain in controls but not in diabetic rats; acute hyperglycemia, in non-treated rats, did not change these effects. Control tail vascular beds showed increased maximal response to phenylephrine after treatment with 10 nM ouabain for 1 h; this response was abolished in streptozotocin-treated rats. These rats showed an increased sensitivity to phenylephrine without changing the maximal vasoconstrictor response when compared to control rats. The relaxation induced by acetylcholine was reduced in diabetic rats. The functional activity of the Na(+),K(+)-ATPase was inhibited in vascular beds from diabetic rats, when compared to control rats, and 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 produced by ouabain is lost as a consequence of the reduction of the functional activity of the Na(+), K(+)-ATPase probably as a result of insulin lack and a deficient endothelial nitric oxide activity.
Davel
A P
AP
Department of Physiological Sciences, Federal University of Espirito Santo, Av. Marechal Campos 1468, 29040-095, ES, Vitoria, Brazil. daltonv2@interlink.com.br
Rossoni
L V
LV
Vassallo
D V
DV
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000502:physiology; D013311:Streptozocin
D004791:Enzyme Inhibitors; D010656:Phenylephrine; D009569:Nitric Oxide; D010042:Ouabain; D013311:Streptozocin; D000254:Sodium-Potassium-Exchanging ATPase