Ouabain amplifies contractile responses to phenylephrine in rat tail arteries in hypertension.
Ouabain, a cardiac glycoside, binds to the alpha-subunits of Na+, K(+)-ATPase and inhibits Na+ pump activity. It has been proposed that endogenous ouabain, by inhibiting vascular Na+, K(+)-ATPase, can increase vascular resistance and thus may contribute to hypertension. One of the consequences of inhibition of the membrane Na+ pump is enhanced responsiveness of vascular smooth muscle to vasopressor substances. The purpose of the present study was to determine whether ouabain can enhance the responsiveness of the vasculature in hypertension. In the present study 100 microM ouabain enhanced the contractile response elicited by phenylephrine in isolated, perfused tail arteries from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. The enhanced contractile response was more pronounced in the arteries of the SHR. We demonstrated that this concentration of ouabain inhibits the Na+ pump activity, measured as ouabain-sensitive 86Rb uptake, by about 65%, in isolated tail arteries. We conclude that ouabain can sensitize the vascular smooth muscle to the effects of vasopressor substances and this effect is more pronounced in genetically hypertensive rats. Endogenous ouabain may contribute to the pathophysiology of hypertension by enhancing vascular tone.
Songu-Mize
E
E
Department of Pharmacology and Experimental Therapeutics, LSU Medical Center, New Orleans 70112, USA.
Vassallo
D V
DV
Rashed
S M
SM
Varner
K J
KJ
D000818:Animals; D001158:Arteries / Q000187:drug effects*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase