betadex and Bradycardia

Farnesol (FAR) is a sesquiterpene alcohol with a range of reported biological effects including cardioprotective, antioxidant and antiarrhythmic properties. However, due to its volatility, the use of drug incorporation systems, such as cyclodextrins, have been proposed to improve its pharmacological properties. Thus, the aim of this study was to evaluate and characterize the cardiovascular effects of FAR alone, and to investigate the antihypertensive effects of FAR complexed with β-cyclodextrin (βCD) in rats. Mean arterial pressure (MAP) and heart rate (HR) were measured before and after intravenous administration of FAR (0,5; 2,5; 5 and 7,5 mg/kg) in normotensive rats, and after oral acute administration (200 mg/kg) of FAR and FAR/βCD complex in NG-nitro-L-arginine-methyl-ester (L-NAME) hypertensive rats. In normotensive animals, FAR induced dose-dependent hypotension associated with bradycardia. These effects were not affected by pre-treatment with L-NAME or indomethacin (INDO), but were partially attenuated by atropine. Pre-treatment with hexamethonium (HEXA) only affected hypotension. In the hypertensive rats, FAR/βCD potentialized the antihypertensive effect when compared to FAR alone. Molecular docking experiments demonstrated for the first time that FAR has affinity to bind to the M

Topics: Animals; Arterial Pressure; beta-Cyclodextrins; Blood Pressure; Bradycardia; Cardiovascular Agents; Dose-Response Relationship, Drug; Enzyme Inhibitors; Farnesol; Heart Rate; Hypertension; Male; Molecular Docking Simulation; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Rats; Rats, Wistar

We studied the aqueous solution of propofol dissolved in hydroxypropyl-beta-cyclodextrin (HP beta CD) 20% to determine whether the cardiovascular profile differed from that measured for propofol prepared in Intralipid 10% (Diprivan). Conscious male rats were given an intravenous bolus of propofol, 5.0 mg/kg, the minimum dose that induces a loss of righting. Immediately severe bradycardia occurred which was the result of a combination of sinus arrest and atrioventricular block; a significant decrease of blood pressure resulted. A bolus of HP beta CD produced no significant changes in heart rate rhythm. The severe bradycardia produced by propofol in HP beta CD was blocked by both atropine and bilateral cervical vagotomy. Therefore, the effects of propofol in HP beta CD are cholinergic and neurally mediated. These results are consistent with the hypothesis that propofol reduces sympathetic tone prior to reduction in vagal tone, and thereby produces a period of time during which vagal tone is dominant.

Topics: Anesthetics, Intravenous; Animals; Arrhythmia, Sinus; Atropine; beta-Cyclodextrins; Bradycardia; Cholinergic Agents; Cyclodextrins; Drug Interactions; Fat Emulsions, Intravenous; Heart; Heart Arrest; Heart Block; Heart Rate; Injections, Intravenous; Male; Pharmaceutical Vehicles; Propofol; Rats; Rats, Sprague-Dawley; Vagotomy; Vagus Nerve