Acute presser actions of ouabain do not enhance the actions of phenylephrine or norepinephrine in anesthetized rats

The inhibition of high-affinity isoforms of the Na+,K+-ATPase by nanomolar levels of ouabain has been proposed to enhance the actions of vasoconstrict or agents that act via a Ca+2-dependent mechanism. The present study tested this hypothesis by evaluating the effects of ouabain (6 and 18 mug/kg, i.v .) on the vasopressor actions of phenylephrine and norepinephrine in anesth etized, reflex-blocked rats. In separate groups of animals, dose-response c urves for increases in diastolic pressure produced by phenylephrine were ge nerated after the administration of saline (control), ouabain (18 mug/kg), L-omega-N-nitro arginine methyl ester (L-NAME, 3 mu mol/kg) and angiotensin II (15 ng/kg per min). Treatment with ouabain (18 mug/kg) produced an incr ease in diastolic pressure of 19 +/- 3 mm Hg but did not significantly alte r the potency or maximal response produced by phenylephrine. In contrast. t reatment with angiotensin II and L-NAME, agents known to enhance the action s of alpha -adrenoceptor agonists, increased the potency of phenylephrine. In animals in which the presser actions of norepinephrine were evaluated be fore and after the administration of ouabain (6 mug/kg), ouabain did not al ter the presser response to norepinephrine. Blockade of alpha -adrenoceptor s with phentolamine was found to attenuate as well as partially reverse the increase in diastolic pressure produced by ouabain. These observations sug gest that ouabain produces a presser response by actions on sympathetic ner ve endings as well as on vascular smooth muscle and that these actions do n ot alter the sensitivity to phenylephrine or norepinephrine.