Effects of ouabain and low sodium on contractility of human resistance arteries.
Earlier work with rat arteries has resulted in a widely held assumption that resistance artery smooth muscle will not contract on exposure to a reduced transplasmalemmal sodium gradient. In view of the well-recognized low sensitivity of rat tissue to cardiac glycosides, we have investigated the effects of altering the transplasmalemmal sodium gradient on vascular smooth muscle tone by using human resistance arteries. Incubation of arteries in low sodium or in ouabain to inhibit active sodium efflux for 1 hour increased the contractile response to caffeine stimulation; this finding indicated enhanced calcium buffering by the sarcoplasmic reticulum. Prolonged incubation in ouabain in the presence of phentolamine or diltiazem resulted in a concentration-dependent increase in the tone of resting human resistance arteries. Reduction of the transplasmalemmal sodium gradient by incubation in low sodium buffer effected an increase in tone similar to that obtained in the presence of ouabain. These results suggest that alteration of the transplasmalemmal sodium gradient may increase the vascular smooth muscle tone of human resistance arteries by altering intracellular calcium handling. This is a new finding in human resistance arteries and may involve inhibition and, indeed, reversal of sodium-dependent calcium efflux. A concentration-dependent potentiation of tone was found after the addition of ouabain to submaximally activated arteries. Sodium-calcium exchange may also play a pivotal role in this mechanism.
Woolfson
R G
RG
Department of Physiology, St Thomas' Hospital, London, UK.
Hilton
P J
PJ
Poston
L
L
D001158:Arteries / Q000187:drug effects / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects*; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014655:Vascular Resistance / Q000187:drug effects*
D002110:Caffeine; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D004110:Diltiazem; D002118:Calcium; D010646:Phentolamine