Ouabain-induced coronary vasoconstriction in cats is not neurally mediated.
1. Previous reports indirectly implicate a neural mechanism for coronary constriction to centrally administered digitalis. However, autoregulatory changes in coronary resistance due to changes in arterial pressure may have influenced the interpretation of these studies. 2. We tested directly the hypothesis that cardiac sympathetic innervation is responsible for coronary constriction to ouabain by examining the effects of ouabain (intravenous (i.v.) and intracerebroventricular (i.c.v.)) before and after bilateral stellate ganglionectomy. 3. Cats were anaesthetized and instrumented for the measurement of heart rate, blood pressure and coronary blood flow velocity using an epicardial-attached suction Doppler probe. Animals were treated with atenolol and the effects of either i.v. or i.c.v. injections of ouabain were examined. 4. In seven cats treated with atenolol, i.v. ouabain (0.11 mg/kg) produced maximal increases in arterial pressure and coronary vascular resistance index (CVRI) of 66 +/- 7 mmHg and 37 +/- 9%, respectively. Following bilateral stellate ganglionectomy (n = 7), ouabain produced similar increases in arterial pressure (70 +/- 9 mmHg) and CVRI (39 +/- 7%). A higher dose of i.v. ouabain (1.1 mg/kg) produced maximal increases in arterial pressure (115 +/- 4 mmHg) and coronary resistance (86 +/- 14%) in intact cats (n = 6) that were similar to responses seen in cats in which stellate ganglionectomy had been performed (n = 6; arterial pressure 104 +/- 13 mmHg; coronary resistance 114 +/- 6%). The increases in coronary resistance to ouabain at both doses were significantly greater than increases in coronary resistance to passive elevation of arterial pressure during aortic constriction. Thus, autoregulation does not explain fully the coronary constriction to ouabain. 5. To further examine a central mechanism, i.c.v. perfusion with 0.3 mmol/L ouabain was performed in six cats, resulting in increases in arterial pressure (122 +/- 7 mmHg) and coronary resistance (58 +/- 14%). Similar increases in arterial pressure (117 +/- 16%) and coronary resistance (84 +/- 20%) were seen in separate studies (n = 6) following stellate ganglionectomy. 6. These results indicate that coronary constriction to ouabain does not require intact cardiac sympathetic innervation, but probably involves a direct or humorally mediated effect.
Nair
B A
BA
VA Medical Center, University of Iowa College of Medicine, Iowa City, IA 53226, USA.
Murad
Y Z
YZ
Brody
M J
MJ
Gutterman
D D
DD
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002415:Cats; D003331:Coronary Vessels / Q000187:drug effects*; D015171:Ganglionectomy; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D010042:Ouabain / Q000008:administration & dosage / Q000494:pharmacology*; D013233:Stellate Ganglion; D013564:Sympathetic Nervous System; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D002316:Cardiotonic Agents; D010042:Ouabain