A CNS serotonergic mechanism in acute central hypovolemia in conscious rabbits?
We tested whether a brainstem serotonergic mechanism influences the hemodynamic response to acute central hypovolemia. An inferior vena caval cuff was gradually inflated so that mean cardiac index (MCI) fell at a constant rate (approximately 8%/min). Under control conditions, mean systemic vascular conductance index (MSVCI) fell progressively until MCI had fallen by approximately 50% (compensatory phase), at which point MSVCI rose abruptly and arterial pressure fell to approximately 40 mm Hg (decompensatory phase). Intravenous methysergide delayed the decompensatory phase and at a critical dose (300-3,000 nmol) abolished it. Methysergide had similar effects when injected into the fourth ventricle, pontomedullary cistern, or lateral ventricle in doses that were 7-10% of the critical i.v. dose, but had no effect when injected into the spinal subarachnoid space. LY53857 was equipotent to methysergide. None of these treatments attenuated the vasoconstriction of the first, compensatory, phase. Partial depletion of neuronal serotonin (after p-chlorophenylalanine or 5,7-dihydroxytryptamine treatment) had no effect on either phase. We conclude that a serotonergic mechanism, probably located in the brainstem, may be involved in the decompensatory phase of acute central hypovolemia.
Evans
R G
RG
Cardiovascular Research Laboratory, University of Melbourne Department of Surgery, Parkville, Victoria, Australia.
Kapoor
V
V
Ludbrook
J
J
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000503:physiopathology*; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008784:Methysergide / Q000008:administration & dosage / Q000494:pharmacology; D011817:Rabbits; D012083:Renin / Q000097:blood; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D012769:Shock / Q000503:physiopathology*
D004873:Ergolines; D012702:Serotonin Antagonists; D001127:Arginine Vasopressin; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D012083:Renin; C032663:LY 53857; D010134:Fenclonine; D008784:Methysergide