Expression of opioid receptors during heart ontogeny in normotensive and hypertensive rats

Reuven Zimlichman, Dov Gefel, Heskel Eliahou, Zipora Matas, Boaz Rosen, Svetlana Gass, Catherine Ela, Yael Eilam, Zvi Vogel, Jacob Barg

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The opioidergic systems are involved in modulating nociceptive stimuli. In addition, recent results suggest that endogenous and exogenous opioids could play a role in the modulation of blood pressure and cardiac functions. However, little is known regarding the expression and role of opioid-binding sites in the heart. The decreased sensitivity to noxious stimuli in hypertensive rats raises the possibility of different developmental pattern expression of opioid-binding sites in normotensive versus hypertensive rats. Methods and Results: Opioid receptor expression in hearts from hypertensive and normotensive rats was studied during heart development by binding assays. From P1 and P90, the development of the heart in the two rat strains was accompanied by a gradual increase in the density of κ-opioid receptors. Hearts from hypertensive rats expressed significantly higher levels of κ receptors compared with those of normotensive rats. At ages older than P7, μ-opioid receptors could not be detected in hearts of both strains, whereas δ-opioid-binding sites gradually increased until reaching adult levels. Seven-day-old cardiomyocyte cultures of both rat strains expressed similar densities of δ or κ receptors to those observed in hearts from 7-day-old neonates. The μ-binding sites were not detected in cardiomyocyte cultures. Similar to the in vivo state, cultured myocytes from hypertensive rats had significantly higher levels of κ-binding sites (1.5- fold) compared with those of normotensive rats. The κ sites are pertussis toxin sensitive, and the state of coupling of the receptor to G protein is similar for the two rat strains. Conclusions: The role of opioid-binding sites in the heart is not completely clear. Hypertensive rats are known to be less sensitive to noxious stimuli compared with normotensive rats. It is controversial whether the site of application of noxious stimuli plays an important role in the sensitivity to pain in hypertensive rats. We suggest that the opioidergic system could play a role in the modulation of blood pressure in addition to its known effect on nociception.

Original languageEnglish
Pages (from-to)1020-1025
Number of pages6
JournalCirculation
Volume93
Issue number5
DOIs
StatePublished - 1 Mar 1996

Keywords

  • cardiomyocytes, cultured
  • hypertension
  • receptors opioid

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