Sodium pump stimulation by activation of two alpha adrenergic receptor subtypes in canine blood vessels.
The effects of alpha-1 and alpha-2 selective adrenergic agents on sodium pump activity were investigated in intact canine femoral artery and saphenous vein by measuring ouabain-sensitive uptake of 86Rb. In both vessels, the alpha-1-selective agonist, phenylephrine, stimulated 86Rb uptake in a dose-dependent manner. The uptake was blocked by prazosin and yohimbine with the order of potency: prazosin greater than yohimbine. The alpha-2-selective agonist, clonidine, also stimulated 86Rb uptake in the saphenous vein but not in the femoral artery. The stimulation was blocked by prazosin and yohimbine with the order of potency: yohimbine greater than prazosin. The potency of phenylephrine to contract saphenous vein or femoral artery was the same as that for stimulation of ouabain-sensitive 86Rb uptake. Clonidine was 10-fold more potent as a contractile agonist than as a Na+ pump stimulant. It caused only a weak contraction in the femoral artery. Reducing extracellular sodium abolished the stimulation of 86Rb uptake by both phenylephrine and clonidine in saphenous vein. Subsequently it was shown that both agonists increased intracellular sodium levels and these increases were blocked by the alpha receptor antagonists, prazosin and yohimbine, with the same selectivity as was observed in the 86Rb uptake experiments. Sodium pump stimulation produced by both phenylephrine and clonidine was blocked by amiloride. These observations suggest that the activity of the vascular sodium pump can be regulated by both alpha-1 and alpha-2 adrenergic receptors and that the mechanism involves an influx of sodium, most likely through a stimulation of Na+/H+ exchange.
Navran
S S
SS
Department of Medicine, Baylor College of Medicine, Houston.
Adair
S E
SE
Jemelka
S K
SK
Seidel
C L
CL
Allen
J C
JC
D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004285:Dogs; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012413:Rubidium / Q000378:metabolism; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D010042:Ouabain; D012964:Sodium; D012413:Rubidium; D003000:Clonidine