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Selective autonomic modulation by mu- and kappa-opioid receptors in the hindbrain
1Department of Physiology, West Virginia School of Osteopathic Medicine, Lewisburg 24901.
Abstract:
In the Nucleus Ambiguus (NA) mu-receptors increased mean arterial pressure (MAP) and heart rate (HR) and kappa-receptors decreased MAP without altering HR. Mu-receptors in the Dorsal Motor Nucleus of the Vagus (DMV) increased MAP without changing HR whereas kappa-receptors in the DMV decreased HR without changing MAP. The pathways which mediate these responses were studied in anesthetized, artificially ventilated rats. Transection of the spinal cord at the C1 segment blocked the pressor response and tachycardia elicited following microinjection of a mu-agonist into the NA. The depressor response elicited by a kappa-agonist was not changed. Complete attenuation of the kappa response was produced by combining spinal transection with bilateral vagotomy. The pressor response produced following microinjection of a mu-agonist into the DMV was attenuated by pretreatment with the sympathetic blocking drug guanethidine. Atropine methyl nitrate pretreatment blocked the bradycardia elicited by a kappa-agonist and revealed an underlying tachycardic response to the mu-agonist. These data show that mu- and kappa-receptors in the NA and DMV modulate cardiovascular activity by selective modulation of sympathetic and parasympathetic pathways.
Insights
Opioid receptors in the brainstem
Area of Science:
- Neuroscience
- Cardiovascular Physiology
- Pharmacology
Background:
- The Nucleus Ambiguus (NA) and Dorsal Motor Nucleus of the Vagus (DMV) are key autonomic control centers.
- Opioid receptors (mu and kappa) are known to influence cardiovascular function.
- Understanding the specific pathways modulated by these receptors is crucial for cardiovascular regulation.
Purpose of the Study:
- To investigate the distinct roles of mu- and kappa-opioid receptors in the NA and DMV.
- To elucidate the neural pathways mediating the cardiovascular effects of these receptors.
- To determine the involvement of sympathetic and parasympathetic systems in these responses.
Main Methods:
- Microinjections of opioid agonists into the NA and DMV of anesthetized rats.
- Spinal cord transection at C1 to assess descending pathways.
- Bilateral vagotomy to evaluate vagal nerve involvement.
- Administration of sympathetic blocking agents (guanethidine) and parasympathetic blockers (atropine methyl nitrate).
- Monitoring of mean arterial pressure (MAP) and heart rate (HR).
Main Results:
- NA mu-receptors increased MAP and HR; kappa-receptors decreased MAP.
- DMV mu-receptors increased MAP; kappa-receptors decreased HR.
- Spinal transection blocked NA mu-receptor-mediated pressor response and tachycardia.
- Vagotomy combined with spinal transection abolished kappa-receptor mediated depressor response from NA.
- Guanethidine attenuated DMV mu-receptor-mediated pressor response.
- Atropine methyl nitrate blocked bradycardia and unmasked tachycardia from DMV kappa-agonists.
Conclusions:
- Mu- and kappa-opioid receptors in the NA and DMV differentially regulate cardiovascular parameters.
- These receptors modulate cardiovascular activity via selective activation of sympathetic and parasympathetic pathways.
- The findings highlight specific neuroanatomical targets for influencing autonomic cardiovascular control.