Acute pressor 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 vasoconstrictor agents that act via a Ca+2-dependent mechanism. The present study tested this hypothesis by evaluating the effects of ouabain (6 and 18 microg/kg, i.v.) on the vasopressor actions of phenylephrine and norepinephrine in anesthetized, reflex-blocked rats. In separate groups of animals, dose-response curves for increases in diastolic pressure produced by phenylephrine were generated after the administration of saline (control), ouabain (18 microg/kg), L-omega-N-nitro arginine methyl ester (L-NAME, 3 micromol/kg) and angiotensin II (15 ng/kg per min). Treatment with ouabain (18 microg/kg) produced an increase in diastolic pressure of 19+/-3 mm Hg but did not significantly alter the potency or maximal response produced by phenylephrine. In contrast, treatment with angiotensin II and L-NAME, agents known to enhance the actions of alpha-adrenoceptor agonists, increased the potency of phenylephrine. In animals in which the pressor actions of norepinephrine were evaluated before and after the administration of ouabain (6 microg/kg), ouabain did not alter the pressor response to norepinephrine. Blockade of alpha-adrenoceptors with phentolamine was found to attenuate as well as partially reverse the increase in diastolic pressure produced by ouabain. These observations suggest that ouabain produces a pressor response by actions on sympathetic nerve endings as well as on vascular smooth muscle and that these actions do not alter the sensitivity to phenylephrine or norepinephrine.
Barker
L A
LA
Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans 70119, USA. lbarke@lsumc.edu
Rossoni
L V
LV
Vassallo
D V
DV
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D000804:Angiotensin II; D010656:Phenylephrine; D010042:Ouabain; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D010646:Phentolamine