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Effect of intracarotid administration of ouabain in dogs
J A Lopez1, A D Timmis, H Garan
1Cardiac Unit, Massachusetts General Hospital, Boston 02114.
Abstract:
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.
Insights
Cardiac glycoside ouabain exhibits dose-dependent effects on blood vessels. Low doses cause vasodilation via the carotid bifurcation, while high doses induce central vasoconstriction.
Area of Science:
- Cardiovascular Physiology
- Neuropharmacology
Background:
- Cardiac glycosides like ouabain can elicit complex neurogenic responses, including vasoconstriction and sympathetic withdrawal.
- Previous studies have documented conflicting vascular effects of cardiac glycosides, suggesting potential underlying mechanisms requiring further investigation.
Purpose of the Study:
- To investigate the dose-dependent relationship between ouabain infusion and neurogenic vascular responses.
- To elucidate the specific mechanisms mediating vasoconstriction and vasodilation induced by ouabain.
Main Methods:
- Ouabain was infused at varying doses (5, 10, 20 micrograms) into the carotid artery of anesthetized dogs.
- Vascular resistance in the gracilis muscle was measured to assess neurogenic effects.
- Studies were conducted with intact and denervated carotid bifurcations to differentiate neural pathways.
Main Results:
- A low dose (5 micrograms) of ouabain induced prolonged vasodilation, mediated by the carotid bifurcation.
- A high dose (20 micrograms) of ouabain caused transient vasoconstriction, independent of the carotid bifurcation.
- An intermediate dose (10 micrograms) had no significant effect on vascular resistance.
Conclusions:
- Ouabain elicits distinct, dose-dependent neurogenic vascular effects.
- Low ouabain doses promote vasodilation through carotid bifurcation pathways.
- High ouabain doses result in central vasoconstriction, overriding other mechanisms.