Mechanism of the hypertensive response to central injection of nicotine in conscious rats.
The purpose of this study was to examine the effects of nicotine administered directly into the CNS on mean arterial pressure (MAP) and heart rate to avoid the direct peripheral action of the drug. Also, because nicotine has been reported to enhance the release of endogenous brain acetylcholine, we sought to determine the role of this mechanism in mediating the cardiovascular response. Normotensive Wistar rats were previously implanted with indwelling intracerebroventricular (ICV) cannula guides and an arterial line (iliac artery) for central injection of drugs and measurement of MAP and heart rate, respectively. Rats received a series of increasing doses of nicotine (or saline vehicle) from 2-100 micrograms (in a 10 microliter volume) with each dose separated by at least 1 day. MAP increased immediately following all doses of nicotine; however, the maximal response was obtained following the 50 micrograms dose (higher doses actually produced lower responses). In general, the hypertensive response began immediately after injection, peaked within 2-3 min and returned to baseline within about 20 min. Heart rate changes were often not dramatic and highly variable. In order to examine the dependence of the pressor response to nicotine on brain acetylcholine, rats were pretreated with 20 micrograms (ICV) of hemicholinium-3 (HC-3) 1 h prior to nicotine to deplete endogenous acetylcholine. HC-3 pretreatment resulted in a significant reduction in the magnitude and duration of the pressor response to nicotine. Likewise, pretreatment with atropine inhibited the pressor response to subsequent injection of nicotine. Nicotine enhanced the release of [3H]acetylcholine from brain slices in vitro at concentrations likely achieved in the in vivo studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Buccafusco
J J
JJ
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30921-2300.
Yang
X
X
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects*; D006426:Hemicholinium 3 / Q000008:administration & dosage / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D006426:Hemicholinium 3; D009538:Nicotine; D001285:Atropine; D000109:Acetylcholine