Cardiovascular effects of (-)-11-OH-delta 8-tetrahydrocannabinol-dimethylheptyl in rats

J Cardiovasc Pharmacol. 1996 Aug;28(2):332-6. doi: 10.1097/00005344-199608000-00022.

Abstract

The effects of the stereochemically pure psychoactive cannabinoid (-)-11-OH-delta 8-tetrahydrocannabinol-dimethylheptyl (HU-210) on blood pressure (BP) and heart rate (HR) were determined in rats. In pentobarbital-anesthetized animals, the compound produced dose-related, long-lasting hypotension and bradycardia at doses between 10 and 1,000 micrograms/kg. BP began to decrease immediately after drug administration, and in no case was an initial pressor response observed. Previous vagotomy (VX) or pretreatment with 6-hydroxydopamine (6-OHDA) did not affect hypotension. Bradycardia was inhibited by VX, but only 60 min after administration of HU-210; it was enhanced by 6-OHDA. The cannabinoid blocked reflex bradycardia induced by phenylephrine (PE). HU-210 also decreased BP and HR in conscious rats. Hypotension lasted 2 h, whereas bradycardia was still present 8 h after drug administration. HU-210 thus shares with delta 9-tetrahydrocannabinol (THC) the ability to decrease BP and HR, but is 5-10 times more potent than the natural compound. Its lack of an initial pressor effect, such as that described for THC, could be related to its specificity for the type-1 cannabinoid (CB1) receptor. Hypotension and bradycardia after HU-210 administration are not due to sympathetic withdrawal. Enhanced parasympathetic tone is involved in bradycardia only at a late stage of the response.

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / pharmacology
  • Baroreflex / drug effects
  • Blood Pressure / drug effects
  • Cardiovascular Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Dronabinol / analogs & derivatives*
  • Dronabinol / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Male
  • Oxidopamine / pharmacology
  • Rats
  • Rats, Wistar
  • Sympatholytics / pharmacology
  • Vagotomy

Substances

  • Anti-Arrhythmia Agents
  • Cardiovascular Agents
  • Excitatory Amino Acid Antagonists
  • Sympatholytics
  • Dronabinol
  • Oxidopamine
  • HU 211