Effect of intracarotid administration of ouabain in dogs.
Recent work has documented both centrally mediated vasoconstriction and, paradoxically, a withdrawal of sympathetic activity in response to cardiac glycosides. In the present study the possibility that these different neurogenic responses might be dose related was investigated by infusing ouabain (5, 10, and 20 micrograms) for 5 min into the right common carotid artery of 51 anesthetized mongrel dogs. Effects on vascular resistance in the isolated, separately perfused but innervated gracilis muscle were measured. A 5-microgram infusion of ouabain (n = 6) produced a prolonged decrease in gracilis vascular resistance (GVR) of 19.4 +/- 5.4% (SE) from 43.4 +/- 6.7 (SE) to 33.7 +/- 4.2 mmHg.ml-1.100 g muscle.min (resistance units, RU). This vasodilatory response was not present in nine additional dogs following denervation of the carotid bifurcation. A 10-microgram infusion had no significant effect on GVR (n = 5), but the 20-microgram infusion of ouabain (n = 8) caused a rapid increase in GVR from 42.1 +/- 5.0 to 47.6 +/- 5.7 RU, an increase of 14.4 +/- 5.6%, which was not influenced by denervation of the carotid bifurcation (n = 8). This vasoconstriction was transient returning toward the control levels by 20 min following the infusion. These data indicate important dose-related differences in vascular responses to ouabain that are directionally opposite and mediated by separate neurogenic mechanisms. At high doses a centrally mediated vasoconstriction dominates, whereas at low doses carotid bifurcation mediated vascular dilatation occurs.
Lopez
J A
JA
Cardiac Unit, Massachusetts General Hospital, Boston 02114.
Timmis
A D
AD
Garan
H
H
Homcy
C J
CJ
Powell
W J
WJ
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000294:innervation; D002346:Carotid Sinus / Q000502:physiology; D003714:Denervation; D004285:Dogs; D005260:Female; D007261:Infusions, Intra-Arterial; D008297:Male; D009132:Muscles / Q000098:blood supply; D010042:Ouabain / Q000008:administration & dosage* / Q000494:pharmacology; D014655:Vascular Resistance; D014661:Vasoconstriction
D010042:Ouabain