Alterations in the Medullary Endocannabinoid System Contribute to Age-related Impairment of Baroreflex Sensitivity

J Cardiovasc Pharmacol. 2015 May;65(5):473-9. doi: 10.1097/FJC.0000000000000216.

Abstract

As they age, Sprague-Dawley (SD) rats develop elevated systolic blood pressure associated with impaired baroreflex sensitivity (BRS) for control of heart rate. We previously demonstrated in young hypertensive (mRen2)27 rats that impaired BRS is restored by CB1 cannabinoid receptor blockade in the solitary tract nucleus (NTS), consistent with elevated content of the endocannabinoid 2-arachidonoylglycerol (2-AG) in dorsal medulla relative to normotensive SD rats. There is no effect of CB1 receptor blockade in young SD rats. We now report in older SD rats that dorsal medullary 2-AG levels are 2-fold higher at 70 versus 15 weeks of age (4.22 ± 0.61 vs. 1.93 ± 0.22 ng/mg tissue; P < 0.05). Furthermore, relative expression of CB1 receptor messenger RNA is significantly lower in aged rats, whereas CB2 receptor messenger RNA is significantly higher. In contrast to young adult SD rats, microinjection of the CB1 receptor antagonist SR141716A (36 pmole) into the NTS of older SD rats normalized BRS in animals exhibiting impaired baseline BRS (0.56 ± 0.06 baseline vs. 1.06 ± 0.05 ms/mm Hg after 60 minutes; P < 0.05). Therefore, this study provides evidence for alterations in the endocannabinoid system within the NTS of older SD rats that contribute to age-related impairment of BRS.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / genetics
  • Aging / metabolism*
  • Animals
  • Arachidonic Acids / metabolism
  • Baroreflex* / drug effects
  • Blood Pressure
  • Cannabinoid Receptor Antagonists / administration & dosage
  • Endocannabinoids / metabolism*
  • Gene Expression Regulation
  • Glycerides / metabolism
  • Heart Rate
  • Male
  • Mass Spectrometry
  • Microinjections
  • Piperidines / administration & dosage
  • Pyrazoles / administration & dosage
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / genetics
  • Receptor, Cannabinoid, CB2 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rimonabant
  • Solitary Nucleus / drug effects
  • Solitary Nucleus / metabolism*

Substances

  • Arachidonic Acids
  • Cannabinoid Receptor Antagonists
  • Cnr1 protein, rat
  • Cnr2 protein, rat
  • Endocannabinoids
  • Glycerides
  • Piperidines
  • Pyrazoles
  • RNA, Messenger
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • glyceryl 2-arachidonate
  • Rimonabant