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Opiate receptors and cardiovascular control in conscious SHR and WKY rats
Abstract:
This study examined the cardiovascular, respiratory, and sympathetic effects of selective mu and delta opioid agonists microinjected into the hypothalamic nucleus preopticus medialis (POM) of conscious SHR and WKY rats. The mu receptor agonist D-Ala2-MePhe4-Gly5-ol-enkephalin (DAGO) at a dose of 0.6 or 6.0 nanomoles (Nmol) increased the blood pressure and heart rate in WKY rats. In SHR rats, the lower dose of DAGO similarly had a pressor effect whereas the higher dose was depressor; heart rat was increased only by the 6.0 nmol dose in these animals. In both SHR and WKY rats, this opioid caused respiratory acidosis and elevation of plasma norepinephrine (NE) and epinephrine (E); plasma vasopressin was reduced by the higher dose of DAGO. All of these effects of the mu agonist were reversed by the opiate receptor antagonist naloxone (0.5 mg/kg, i.a.). The delta opiate-receptor agonist D-Ala2-D-leu5-eukephalin at a dose of 6.0 or 20.0 nmol increased blood pressure and heart rate in both SHR and WKY rats without affecting respiratory variables. Plasma NE and EPI were elevated at the peak of the pressor period. These studies suggest that the anteroventral hypothalamic region may be an important site in central autonomic regulation by opioid peptides. The mu-receptor agonist was more potent than the delta agonist in eliciting cardiovascular and respiratory effects and associated sympatho-adrenomedullary activation.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Selective opioid agonists in the hypothalamus affect cardiovascular and respiratory functions. Mu-opioid agonists showed greater potency than delta-opioid agonists in altering autonomic responses and activating the sympatho-adrenomedullary system.
Area of Science:
- Neuroscience
- Cardiovascular Physiology
- Autonomic Nervous System
Background:
- The hypothalamus plays a crucial role in regulating cardiovascular and respiratory functions.
- Opioid peptides are known to influence autonomic outflow.
- Previous research has not fully elucidated the specific roles of mu and delta opioid receptors in the hypothalamic nucleus preopticus medialis (POM).
Purpose of the Study:
- To investigate the cardiovascular, respiratory, and sympathetic effects of selective mu and delta opioid agonists microinjected into the hypothalamic POM in conscious rats.
- To compare the potency of mu and delta opioid agonists in eliciting autonomic responses.
Main Methods:
- Microinjection of selective mu (DAGO) and delta (DALA) opioid agonists into the hypothalamic POM of conscious Spontaneously Hypertensive Rats (SHR) and Wistar-Kyoto (WKY) rats.
- Measurement of cardiovascular parameters (blood pressure, heart rate), respiratory variables, and plasma levels of norepinephrine (NE), epinephrine (E), and vasopressin.
- Administration of naloxone to assess the involvement of opioid receptors.
Main Results:
- Mu-opioid agonist (DAGO) administration caused dose-dependent pressor and heart rate effects in WKY rats, with varied responses in SHR rats.
- DAGO induced respiratory acidosis and elevated plasma NE and E in both rat strains, while reducing vasopressin at higher doses.
- Delta-opioid agonist (DALA) increased blood pressure and heart rate without affecting respiratory variables, but elevated plasma NE and E.
- All effects of DAGO were reversed by naloxone.
Conclusions:
- The anteroventral hypothalamic region, specifically the POM, is a significant site for central autonomic regulation by opioid peptides.
- Mu-opioid receptor agonists are more potent than delta-opioid receptor agonists in modulating cardiovascular and respiratory functions and activating the sympatho-adrenomedullary system.