Regional haemodynamic effects of mu-, delta-, and kappa-opioid agonists microinjected into the hypothalamic paraventricular nuclei of conscious, unrestrained rats

Br J Pharmacol. 1995 Jun;115(4):613-21. doi: 10.1111/j.1476-5381.1995.tb14976.x.

Abstract

1. The cardiovascular effects of bilateral injection into the hypothalamic paraventricular nuclei of selective mu-, delta-, and kappa-opioid receptor agonists were investigated in conscious, unrestrained Wistar Kyoto rats, chronically instrumented with pulsed Doppler flow probes for measurement of regional haemodynamics. 2. The selective mu-agonist [D-Ala2,MePhe4,Gly5ol]enkephalin (DAMGO), injected bilaterally into the hypothalamic paraventricular nuclei (0.01-1.0 nmol), caused increases in blood pressure, tachycardias, vasoconstriction in renal and superior mesenteric vascular beds and substantial vasodilatation in the hindquarter vascular bed. 3. The administration of increasing doses (0.01-5.0 nmol) of the selective delta-agonist [D-Phe2,5]enkephalin (DPDPE) or the selective kappa-agonist, U50488H into the paraventricular nuclei (PVN) had no significant effect on blood pressure, heart rate, or regional haemodynamics. 4. Together, the present results are further evidence of a role for opioid peptides, especially acting at mu-receptors in the PVN, in the central regulation of the cardiovascular system, whereas a role for opioid peptides, acting at delta- and kappa-receptors in the PVN, seems less obvious from the present results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Analgesics / administration & dosage
  • Analgesics / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology
  • Blood Pressure / drug effects
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalin, D-Penicillamine (2,5)-
  • Enkephalins / administration & dosage
  • Enkephalins / pharmacology
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Hindlimb / blood supply
  • Hindlimb / drug effects
  • Laser-Doppler Flowmetry
  • Male
  • Mesenteric Arteries / drug effects
  • Microinjections
  • Paraventricular Hypothalamic Nucleus / drug effects*
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Inbred WKY
  • Receptors, Opioid, delta / agonists*
  • Receptors, Opioid, kappa / agonists*
  • Receptors, Opioid, mu / agonists*
  • Renal Artery / drug effects
  • Tachycardia / chemically induced
  • Vasoconstriction / drug effects
  • Vasodilation / drug effects

Substances

  • Analgesics
  • Antihypertensive Agents
  • Enkephalins
  • Pyrrolidines
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Enkephalin, D-Penicillamine (2,5)-