EXPRESSION OF OPIOID RECEPTORS DURING HEART ONTOGENY IN NORMOTENSIVE AND HYPERTENSIVE RATS

Background The opioidergic systems are involved in modulating nocicept ive stimuli. In addition, recent results suggest that endogenous and e xogenous opioids could play a role in the modulation of blood pressure and cardiac functions. However, little is known regarding the express ion and role of opioid-binding sites in the heart. The decreased sensi tivity 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 r eceptor expression in hearts from hypertensive and normotensive rats w as studied during heart development by binding assays. From P1 until P 90, the development of the heart in the two rat strains was accompanie d by a gradual increase in the density of kappa-opioid receptors. Hear ts from hypertensive rats expressed significantly higher levels of kap pa receptors compared with those of normotensive rats. At ages older t han P7, mu-opioid receptors could not be detected in hearts of both st rains, whereas delta-opioid-binding sites gradually increased until re aching adult levels. Seven-day-old cardiomyocyte cultures of both rat strains expressed similar densities of delta or kappa receptors to tho se observed in hearts from 7-day-old neonates. The mu-binding sites we re not detected in cardiomyocyte cultures. Similar to the in vivo stat e, cultured myocytes from hypertensive rats had significantly higher l evels of kappa-binding sites (1.5-fold) compared with those of normote nsive rats. The kappa sites are pertussis toxin sensitive, and the sta te 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 sensitiv e to noxious stimuli compared with normotensive rats. It is controvers ial whether the site of application of noxious stimuli plays an import ant role in the sensitivity to pain in hypertensive rats. We suggest t hat the opioidergic system could play a role in the modulation of bloo d pressure in addition to its known effect on nociception.