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.
Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans 70119, USA. lbarke@lsumc.edu
L A
LA
Barker
L V
LV
Rossoni
D V
DV
Vassallo
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