Contribution of baroreflex sensitivity and vascular reactivity to variable haemodynamic responses to cocaine in conscious rats.
1. Baroreflex function is critical for short-term arterial pressure regulation and decreased baroreflex responsivity may predict a predisposition to hypertension and sudden cardiac death. In the present study, we assessed whether baroreflex sensitivity (BRS) and/or vascular reactivity covary with haemodynamic responsiveness to cocaine in vascular and mixed responders. 2. We assessed the heart rate index of BRS in resting animals. We examined dose-response relationships to pressor and depressor agents to determine cardiovascular reactivity. Subsequently, rats were given cocaine (5 mg/kg, i.v.) to classify them as vascular or mixed responders. Vascular responders (n=16) were defined as those rats with a substantial (>8%) decrease in cardiac output in response to cocaine owing to a larger increase in systemic vascular resistance. The remaining rats (n=8) were mixed responders because they had smaller increases in vascular resistance and little change or an increase in cardiac output. 3. The BRS determined with angiotensin (Ang) II, but not with phenylephrine, was impaired in mixed responders compared with vascular responders. At equipressor doses, there were significantly greater reductions in cardiac output in vascular responders compared with mixed responders in response to phenylephrine or AngII. Methacholine produced greater decreases in heart rate in vascular responders, suggesting greater muscarinic responsivity. 4. We conclude that differences in vascular reactivity to AngII may contribute to differences in haemodynamic response profiles to cocaine in individual rats. More importantly, the differences in vascular responsivity and BRS do not appear to be primary determinants of haemodynamic response variability.
Traub
Michael
M
Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, St Louis, Missouri 63104, USA.
Aochi
Tamiko
T
Kawada
Toru
T
Shishido
Toshiaki
T
Sunagawa
Kenji
K
Knuepfer
Mark M
MM
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D018765:Dopamine Uptake Inhibitors; D018721:Muscarinic Agonists; D014662:Vasoconstrictor Agents; D016210:Methacholine Chloride; D000804:Angiotensin II; D010656:Phenylephrine; D003042:Cocaine