Changes in nociception, arterial blood pressure and heart rate produced by intravenous morphine in the conscious rat

Thurston, C.L.; Starnes, Austin C.; Randich, Alan

doi:10.1016/0006-8993(93)91645-9

Cited by 17 publications

(5 citation statements)

References 13 publications

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“…This study also confirms the findings of Grinnell et al (2014) that morphine elicits a substantial decrease in tissue oxygenation saturation (SpO 2 ) in rats. The administration of the 10 mg/kg dose of morphine elicited relatively minor reductions in DBP, SBP and MAP in our freely-moving rats with the available literature reporting minimal to substantial reductions in these parameters in nonanesthetized rats (Della Puppa et al, 1989;Thornhill et al, 1989;Thurston et al, 1993). Consistent with published literature, morphine also elicited robust and sustained decreases in heart rate, which have been reported to mainly involve an increase in vagal drive to the heart (Della Puppa et al, 1989;Thornhill et al, 1989;Thurston et al, 1993).…”

Section: Discussionsupporting

confidence: 89%

“…The administration of the 10 mg/kg dose of morphine elicited relatively minor reductions in DBP, SBP and MAP in our freely-moving rats with the available literature reporting minimal to substantial reductions in these parameters in non-anesthetized rats ( Della Puppa et al, 1989 ; Thornhill et al, 1989 ; Thurston et al, 1993 ). Consistent with published literature, morphine also elicited robust and sustained decreases in heart rate, which have been reported to mainly involve an increase in vagal drive to the heart ( Della Puppa et al, 1989 ; Thornhill et al, 1989 ; Thurston et al, 1993 ). The ratio of heart rate/MAP can be taken as an index of baroreceptor reflex activity ( Lewis et al, 1999 ; Salman et al, 2020 ), and our data provide evidence that morphine decreased this ratio and therefore potentially decreased the activity of the baroreflex in our rats.…”

Section: Discussionsupporting

confidence: 69%

“…Rather remarkably, the injection of Tempol (either 60 or 100 mg/kg) caused a pronounced and sustained increase in heart rate by mechanisms that we are currently exploring. We can only conjecture that Tempol somehow inhibits the signaling central signaling pathways by which morphine diminishes heart rate, including the activation of vagal drive (Della Puppa et al, 1989;Thornhill et al, 1989;Thurston et al, 1993). It is also important to consider the possibility that the increase in ventilation and improvements in gas-exchange within the lungs and therefore ABG chemistry following Tempol administration in morphinetreated rats, may be a result of the large reduction in blood pressure elicited by Tempol.…”

Section: Discussionmentioning

confidence: 99%

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Tempol Reverses the Negative Effects of Morphine on Arterial Blood-Gas Chemistry and Tissue Oxygen Saturation in Freely-Moving Rats

Baby¹,

Discala²,

Gruber³

et al. 2021

Front. Pharmacol.

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We have reported that pretreatment with the clinically approved superoxide dismutase mimetic, Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), blunts the cardiorespiratory depressant responses elicited by a subsequent injection of fentanyl, in halothane-anesthetized rats. The objective of the present study was to determine whether Tempol is able to reverse the effects of morphine on arterial blood-gas (ABG) chemistry in freely-moving Sprague Dawley rats. The intravenous injection of morphine (10 mg/kg) elicited substantial decreases in pH, pO2 and sO2 that were accompanied by substantial increases in pCO2 and Alveolar-arterial gradient, which results in diminished gas-exchange within the lungs. Intravenous injection of a 60 mg/kg dose of Tempol 15 min after the injection of morphine caused minor improvements in pO2 and pCO2 but not in other ABG parameters. In contrast, the 100 mg/kg dose of Tempol caused an immediate and sustained reversal of the negative effects of morphine on arterial blood pH, pCO2, pO2, sO2 and Alveolar-arterial gradient. In other rats, we used pulse oximetry to determine that the 100 mg/kg dose of Tempol, but not the 60 mg/kg dose elicited a rapid and sustained reversal of the negative effects of morphine (10 mg/kg, IV) on tissue O2 saturation (SpO2). The injection of morphine caused a relatively minor fall in mean arterial blood pressure that was somewhat exacerbated by Tempol. These findings demonstrate that Tempol can reverse the negative effects of morphine on ABG chemistry in freely-moving rats paving the way of structure-activity and mechanisms of action studies with the host of Tempol analogues that are commercially available.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

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Tempol Reverses the Negative Effects of Morphine on Arterial Blood-Gas Chemistry and Tissue Oxygen Saturation in Freely-Moving Rats

Baby¹,

Discala²,

Gruber³

et al. 2021

Front. Pharmacol.

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“…Endogenous and exogenous opioids regulate the performance of BRS throughout infl uencing central opioids receptors, including Mu and Kappa (48).…”

Section: Discussionmentioning

confidence: 99%

Morphine and nicotine addiction and withdrawal influence baroreflex sensitivity and blood pressure in two-kidney one clip hypertensive (2K1C) rats

Zeinivand¹,

Shamsizadeh²,

Pourshanazari³

et al. 2014

BLL

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Abstract:Objective: This study aimed to investigate the effects of addiction to morphine and nicotine as well as their withdrawal on both barorefl ex sensitivity and blood pressure in hypertensive rats. Methods: In this experimental study 40 male rats were divided into two main groups as follows: in group I, hypertensive rats received saline for 8 weeks; in group II, hypertensive rats were treated with morphine and nicotine for 8 weeks. At the end of 8 weeks group II rats were divided into four sub-groups including, 3 sub-groups of those were put on drug withdrawal protocol. At the end of experiment, blood pressure, heart rate, plasma renin activity (PRA), serum NO concentration and barorefl ex sensitivity (BRS) were measured. Results: Results demonstrated that BP and BRS were signifi cantly lower in addicted to morphine and nicotine hypertensive rats compared to control (p < 0.05). Addiction withdrawal (in morphine and nicotine withdrawal rats) completely reversed BP and BRS to the pre-addiction levels (p < 0.05). Withdrawal in the only nicotine treated group lowered BP and BRS compared to group that had received morphine and nicotine together (p < 0.05). Conclusion: Results of current study may propose simultaneous morphine and nicotine withdrawal can prevent cardiovascular complications raised due to withdrawal (Fig. 5, Ref. 58). Text in PDF www.elis.sk.

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“…Opioids can indirectly alter cardiac function via inhibitory actions on the autonomic nervous system or CNS. 4,5 Furthermore, opioids may directly alter cardiac contractility…”

mentioning

confidence: 99%

Cardiovascular effects of fentanyl and propofol on hemodynamic function in rabbits

Baumgartner¹,

Koenighaus²,

Ebner³

et al. 2009

ajvr

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Changes in nociception, arterial blood pressure and heart rate produced by intravenous morphine in the conscious rat

Cited by 17 publications

References 13 publications

Tempol Reverses the Negative Effects of Morphine on Arterial Blood-Gas Chemistry and Tissue Oxygen Saturation in Freely-Moving Rats

Tempol Reverses the Negative Effects of Morphine on Arterial Blood-Gas Chemistry and Tissue Oxygen Saturation in Freely-Moving Rats

Morphine and nicotine addiction and withdrawal influence baroreflex sensitivity and blood pressure in two-kidney one clip hypertensive (2K1C) rats

Cardiovascular effects of fentanyl and propofol on hemodynamic function in rabbits

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