Vasopressin induced myocardial depression in neurally mediated and not due to impaired coronary blood flow.
The mechanism of the cardiodepressant effect of vasopressin was studied by measuring simultaneously myocardial contractile force and coronary blood flow (with tracer microspheres) in anaesthetized open-chest rabbits. Lysine-vasopressin administered at two dose levels (10 and 100 mu kg-1 infused in 2 min with a maintenance dose of 2 mu kg-1 min-1 between these two loading doses) to a group of 6 rabbits caused dose-dependent myocardial depression and also severely decreased coronary blood flow in a dose-dependent manner. Blood pressure remained almost unchanged but heart rate, cardiac output and total peripheral conductance were also decreased dose-dependently. In another group of 6 rabbits treated in the same way with lysine-vasopressin, darodipine (PY 108-068, 30 and 100 micrograms kg-1) was infused intravenously. It reversed the vasopressin-induced coronary constriction and cardiodepression. The high dose of vasopressin brought back cardiac depression but did not reduce coronary blood flow below baseline values. Myocardial depression could therefore not be adequately explained by the changes in coronary blood flow. In a further group of rabbits which had been subjected to cervical vagotomy and beta-adrenoceptor blockade (propranolol 1 mg kg-1 i.v.) before the experiment, vasopressin still caused coronary constriction which was reversed by darodipine, but had no effect on myocardial contractile force and heart rate. The cardiodepressant effect of vasopressin can thus be explained fully by effects on the autonomic nervous system which are reversed by lowering blood pressure, whereas the severe reduction of coronary flow did not contribute to the vasopressin-induced myocardial depression.
D000818:Animals; D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008236:Lypressin / Q000494:pharmacology*; D008863:Microspheres; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D012018:Reflex / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D008236:Lypressin; D009543:Nifedipine; C034600:darodipine