(Circulation. 1996;93:1020-1025.)
© 1996 American Heart Association, Inc.
Articles |
Expression of Opioid Receptors During Heart Ontogeny in Normotensive and Hypertensive Rats
From the Department of Internal Medicine (R.Z., D.G., B.R.), Hypertension Clinic (H.E.), Clinical Chemistry Laboratory (Z.M.), and Cardiovascular and Hypertension Research Laboratory (S.G., J.B.), Wolfson Medical Center, Tel Aviv University Sackler School of Medicine, Holon, Israel; Department of Bacteriology (C.E., Y.E.), Hebrew University-Hadassah Medical School, Jerusalem, Israel; Department of Neurobiology (Z.V., J.B.), Weizmann Institute of Science, Rehovot, Israel; and Therapeutic Community (J.B.), Ramot Yehuda, Zoharim, Israel.
Correspondence to Jacob Barg, MD, Cardiovascular and Hypertension Research Laboratory, Wolfson Medical Center, Box 5, 58100 Holon, Israel. E-mail bnbarg@weizmann.weizmann.ac.il.
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 until P90, the development of
the heart in the two rat strains was accompanied by a gradual increase
in the density of 
-opioid receptors. Hearts from hypertensive
rats expressed significantly higher levels of 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
-opioid–binding sites gradually increased until reaching
adult levels. Seven-day-old cardiomyocyte cultures
of both rat strains expressed similar densities of or 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 -binding
sites (1.5-fold) compared with those of normotensive rats. The
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.
Key Words: receptors, opioid • cardiomyocytes, cultured • hypertension
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