The cardiovascular responses to mu opioid agonist and antagonist in conscious normal and obese rats

Peptides. 2006 Jun;27(6):1520-6. doi: 10.1016/j.peptides.2005.10.012. Epub 2005 Nov 15.

Abstract

Beta-endorphin decreases blood pressure in normal rats but increases blood pressure in obese rats. Since beta-endorphins can bind both mu opioid and kappa-opioid receptors we investigated the effect of a mu specific receptor agonist, D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and a mu specific antagonist, D-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) on cardiovascular responses in conscious control and obese rats. Rats were also implanted with telemetry transmitters and intracerebroventricular (ICV) cannulas for recording and peptide administration. The mu agonist, DAMGO, increased blood pressure (BP) in control rats. DAMGO also increased BP in obese rats but only at high concentrations. The heart rate responses paralleled the MAP responses. CTAP, the mu antagonist, paradoxically increased the MAP in both control and obese rats. The responsiveness to the mu agonist and antagonist was greater in controls. In other animals the brains were excised and the ventral medial hypothalamic area removed and mu receptor expression determined using PCR. The expression of mu opioid receptors was increased in obese rats. We conclude that the mu opioids can stimulate cardiovascular responses, but the excitatory responsiveness was not increased in conscious obese rats.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Animals
  • Blood Pressure
  • Cardiovascular System / metabolism*
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Male
  • Narcotic Antagonists / pharmacology
  • Obesity / genetics
  • Obesity / metabolism
  • Peptide Fragments
  • Peptides / chemistry
  • Peptides / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Opioid, mu / agonists*
  • Receptors, Opioid, mu / antagonists & inhibitors*
  • Somatostatin
  • Telemetry

Substances

  • Analgesics, Opioid
  • CTAP octapeptide
  • Narcotic Antagonists
  • Peptide Fragments
  • Peptides
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Somatostatin