Respiratory and cardiovascular effects of the μ‐opioid receptor agonist [Lys<sup>7</sup>]dermorphin in awake rats

Negri, Lucia; Lattanzi, Roberta; Tabacco, Fabio; Melchiorri, Pietro

doi:10.1038/sj.bjp.0701823

Cited by 19 publications

(3 citation statements)

References 42 publications

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“…The MAP-lowering activity of loperamide likely occurs through the activation of opioid receptors in peripheral tissues because loperamide does not cross the blood-brain barrier [9] . Furthermore, 1 -opioid receptors probably play only a minor role in this process because loperamide's effects were minimally affected by naloxonazine pretreatment; this view is consistent with a previous report [25] .…”

Section: Discussionsupporting

confidence: 81%

Activation of Peripheral Opioid µ-Receptors in Blood Vessel May Lower Blood Pressure in Spontaneously Hypertensive Rats

Chen

Shieh²,

Chung

et al. 2011

Pharmacology

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Background/Aims: The role of opioid receptors in the regulation of vascular function remains unclear. In the current study, we evaluated the ability of loperamide, a peripheral opioid receptor agonist, to regulate blood pressure in spontaneously hypertensive rats (SHRs) and examined the mechanism(s) by which loperamide exerts its effects. Methods: In male SHRs, mean arterial pressure (MAP) was measured and hemodynamic analysis was recorded. Additionally, the isometric tension of aortic rings isolated from SHRs was determined. Results: Loperamide dose-dependently decreased MAP in SHRs but not in the normal group of Wistar-Kyoto rats. This reduction of MAP in conscious SHRs was abolished by the selective opioid µ-receptor antagonist cyprodime, but not by naloxonazine, the µ₁-opioid receptor antagonist. However, cardiac output was not altered by loperamide in anesthetized SHRs. Moreover, loperamide-induced relaxation in isolated aortic rings precontracted with phenylephrine or vasopressin. This relaxation was abolished by cyprodime, but not by naloxonazine. Loperamide-induced relaxation was also attenuated by glibenclamide, an ATP-sensitive potassium (K_ATP) channel blocker. Additionally, vasodilatation by loperamide was reduced by an inhibitor of protein kinase A (PKA) and enhanced by an inhibitor of phosphodiesterases. Conclusion: We suggest that loperamide can lower MAP in SHRs via µ₂-opioid receptor-dependent cAMP-PKA pathway that induces vascular relaxation by opening K_ATP channels.

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Section: Discussionsupporting

confidence: 81%

Activation of Peripheral Opioid µ-Receptors in Blood Vessel May Lower Blood Pressure in Spontaneously Hypertensive Rats

Chen

Shieh²,

Chung

et al. 2011

Pharmacology

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“…In these studies, the increased tidal volume was unable to fully compensate for the frequency decrease, and thus minute volume was generally depressed after opioid treatment, as reported for most opioid studies on respiration (Isom et al, 1969;van den Hoogen and Colpaert, 1986). Several other studies have, however, observed either no effect or an increase in minute volume with the administration of various doses of opioid agonists, emphasising that some respiratory effects of opioids remain unresolved (Czapla et al, 2000;Kokka et al, 1965;Negri et al, 1998). These effects, however, may be methadone specific due to its ability to act on both opioid and non-opioid (NMDA receptor) sites (Gorman et al, 1997).…”

Section: Discussionmentioning

confidence: 93%

Reversal of morphine, methadone and heroin induced effects in mice by naloxone methiodide

2006

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“…This increase of ventilation, after inhibiting central opioid receptors, observed at 2, 5, and 10 minutes of hypoxia seems to be attenuated by decreased breathing frequency at 20 minutes of hypoxia. A recent study shows that analgesic doses of [Lys7] dermorphin stimulate respiration (as opposed to ventilatory depression) by activating central μ opioid receptors, and this respiratory stimulation involves activation of a forebrain serotoninergic excitatory pathway during both room air and hypoxic exposures (27). This important observation indicates that different brain locations, neurointeractions, and different types of opioid receptors may result in different effects on respiratory neuron and respiratory effector responses.…”

Section: Discussionmentioning

confidence: 99%

Opioidergic Modulation of Ventilatory Response to Sustained Hypoxia in Obese Zucker Rats

et al. 2001

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) and eight obese (225 Ϯ 12 g) Zucker rats were studied at 6 weeks of age. Pulmonary ventilation (V E ), tidal volume (V T ), and breathing frequency (f) at rest and in response to sustained (30 minutes) hypoxic (10% O 2 ) challenges were measured on three separate occasions by the barometric method after the randomized, blinded administration of equal volumes of saline (control), naloxone methiodide (N M ; 5 mg/kg, peripheral opioid antagonist), or naloxone hydrochloride (N HCl ; 5 mg/kg, peripheral and central opioid antagonist). Results: Administration of N M and N HCl in lean animals had no effect on V E either at rest or during 30 minutes of sustained exposure to hypoxia. Similarly, N M failed to alter V E in obese rats. In contrast, N HCl significantly (p Ͻ 0.05) increased V E and V T both at rest and during 2 to 10 minutes of hypoxic exposure in obese rats. After 20 to 30 minutes of hypoxic exposure, V T remained elevated with N HCl , but the earlier elevation of V E seemed to be attenuated due to a decrease in f at 20 minutes of exposure to hypoxia. Discussion: Thus, endogenous opioids modulate both resting V E and the ventilatory response to sustained hypoxia in obese, but not in lean, Zucker rats by acting specifically on opioid receptors located within the central nervous system.

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Respiratory and cardiovascular effects of the μ‐opioid receptor agonist [Lys⁷]dermorphin in awake rats

Abstract: 1 Changes in respiratory variables, arterial blood pressure and heart rate were studied in awake rats after injection of the opioid peptide [Lys 7 ]dermorphin and its main metabolites, [1][2][3][4][5]

Cited by 19 publications

References 42 publications

Activation of Peripheral Opioid µ-Receptors in Blood Vessel May Lower Blood Pressure in Spontaneously Hypertensive Rats

Activation of Peripheral Opioid µ-Receptors in Blood Vessel May Lower Blood Pressure in Spontaneously Hypertensive Rats

Reversal of morphine, methadone and heroin induced effects in mice by naloxone methiodide

Opioidergic Modulation of Ventilatory Response to Sustained Hypoxia in Obese Zucker Rats

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Respiratory and cardiovascular effects of the μ‐opioid receptor agonist [Lys7]dermorphin in awake rats

Abstract: 1 Changes in respiratory variables, arterial blood pressure and heart rate were studied in awake rats after injection of the opioid peptide [Lys 7 ]dermorphin and its main metabolites, [1][2][3][4][5]

Cited by 19 publications

References 42 publications

Activation of Peripheral Opioid µ-Receptors in Blood Vessel May Lower Blood Pressure in Spontaneously Hypertensive Rats

Activation of Peripheral Opioid µ-Receptors in Blood Vessel May Lower Blood Pressure in Spontaneously Hypertensive Rats

Reversal of morphine, methadone and heroin induced effects in mice by naloxone methiodide

Opioidergic Modulation of Ventilatory Response to Sustained Hypoxia in Obese Zucker Rats

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Respiratory and cardiovascular effects of the μ‐opioid receptor agonist [Lys⁷]dermorphin in awake rats