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Systemic leptin produces a long-lasting increase in respiratory motor output in rats.

Chang Z, Ballou E, Jiao W, McKenna KE, Morrison SF, McCrimmon DR - Front Physiol (2013)

Bottom Line: The increase peaked at 90 min at 58.3 ± 5.7% above baseline.There was an associated increase in the slope of the phrenic response to increasing inspired CO(2).There was also a moderate and sustained decrease in arterial pressure 9 ± 1.3 mmHg at 120 min, with no associated change in heart rate.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University Chicago, IL, USA.

ABSTRACT
Leptin decreases food intake and increases energy expenditure. Leptin administration into the CNS of mice or rats increases alveolar ventilation and dysfunction in leptin signaling has been implicated in the hypoventilation that can accompany obesity. An increase in CO(2) chemosensitivity has been implicated in this response but it is unclear whether ventilation is augmented when PCO(2) is maintained constant. We examined the effects of intravenous leptin to test the hypothesis that systemic leptin administration in isoflurane anesthetized, mechanically ventilated and vagotomized rats would lead to a sustained increase in respiratory motor output that was independent of changes in end-tidal PCO(2), body temperature or lung inflation pressure (an indicator of overall lung and chest wall compliance). In anesthetized Sprague-Dawley rats with end-tidal PCO(2), lung compliance and rectal temperature maintained constant, injection of a bolus of leptin (0.25 mg, 0.5 mg/ml, i.v.), followed over the next 1 h by the intravenous infusion of an additional 0.25 mg, elicited a progressive increase in the peak amplitude of integrated phrenic nerve discharge lasting at least 1 h beyond the end of the infusion. The increase peaked at 90 min at 58.3 ± 5.7% above baseline. There was an associated increase in the slope of the phrenic response to increasing inspired CO(2). There was also a moderate and sustained decrease in arterial pressure 9 ± 1.3 mmHg at 120 min, with no associated change in heart rate. These data indicate that leptin elicits a sustained increase in respiratory motor output that outlasts the administration leptin via a mechanism that does not require alterations in arterial PCO(2), body temperature, or systemic afferent feedback via the vagus nerves. This stimulation may help to prevent obesity-related hypoventilation.

No MeSH data available.


Related in: MedlinePlus

Integrated phrenic nerve amplitude (∫Phr normalized to baseline) and burst frequency (Resp Freq) at baseline (0 min) and at 15 min intervals for the experiment in Figure 1 (leptin; n = 6 except as indicated on graph; control, lactated Ringer's; n = 4 except as indicated). Note the selective increase in ∫Phrenic in leptin treated rats, *p < 0.05.
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Figure 2: Integrated phrenic nerve amplitude (∫Phr normalized to baseline) and burst frequency (Resp Freq) at baseline (0 min) and at 15 min intervals for the experiment in Figure 1 (leptin; n = 6 except as indicated on graph; control, lactated Ringer's; n = 4 except as indicated). Note the selective increase in ∫Phrenic in leptin treated rats, *p < 0.05.

Mentions: Injection of a bolus of leptin (250 μg, i.v.), followed over the next hour by the intravenous infusion of an additional 250 μg, elicited a progressive increase in phrenic nerve discharge (Figures 1A, 2; n = 5 − 6; p < 0.05) lasting at least 1 h beyond the end of the infusion. In contrast, intravenous injection of the vehicle (lactated Ringer's containing phosphate buffered saline; Figures 1B, 2; n = 2 − 4) elicited no significant change in respiratory motor output.


Systemic leptin produces a long-lasting increase in respiratory motor output in rats.

Chang Z, Ballou E, Jiao W, McKenna KE, Morrison SF, McCrimmon DR - Front Physiol (2013)

Integrated phrenic nerve amplitude (∫Phr normalized to baseline) and burst frequency (Resp Freq) at baseline (0 min) and at 15 min intervals for the experiment in Figure 1 (leptin; n = 6 except as indicated on graph; control, lactated Ringer's; n = 4 except as indicated). Note the selective increase in ∫Phrenic in leptin treated rats, *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569609&req=5

Figure 2: Integrated phrenic nerve amplitude (∫Phr normalized to baseline) and burst frequency (Resp Freq) at baseline (0 min) and at 15 min intervals for the experiment in Figure 1 (leptin; n = 6 except as indicated on graph; control, lactated Ringer's; n = 4 except as indicated). Note the selective increase in ∫Phrenic in leptin treated rats, *p < 0.05.
Mentions: Injection of a bolus of leptin (250 μg, i.v.), followed over the next hour by the intravenous infusion of an additional 250 μg, elicited a progressive increase in phrenic nerve discharge (Figures 1A, 2; n = 5 − 6; p < 0.05) lasting at least 1 h beyond the end of the infusion. In contrast, intravenous injection of the vehicle (lactated Ringer's containing phosphate buffered saline; Figures 1B, 2; n = 2 − 4) elicited no significant change in respiratory motor output.

Bottom Line: The increase peaked at 90 min at 58.3 ± 5.7% above baseline.There was an associated increase in the slope of the phrenic response to increasing inspired CO(2).There was also a moderate and sustained decrease in arterial pressure 9 ± 1.3 mmHg at 120 min, with no associated change in heart rate.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University Chicago, IL, USA.

ABSTRACT
Leptin decreases food intake and increases energy expenditure. Leptin administration into the CNS of mice or rats increases alveolar ventilation and dysfunction in leptin signaling has been implicated in the hypoventilation that can accompany obesity. An increase in CO(2) chemosensitivity has been implicated in this response but it is unclear whether ventilation is augmented when PCO(2) is maintained constant. We examined the effects of intravenous leptin to test the hypothesis that systemic leptin administration in isoflurane anesthetized, mechanically ventilated and vagotomized rats would lead to a sustained increase in respiratory motor output that was independent of changes in end-tidal PCO(2), body temperature or lung inflation pressure (an indicator of overall lung and chest wall compliance). In anesthetized Sprague-Dawley rats with end-tidal PCO(2), lung compliance and rectal temperature maintained constant, injection of a bolus of leptin (0.25 mg, 0.5 mg/ml, i.v.), followed over the next 1 h by the intravenous infusion of an additional 0.25 mg, elicited a progressive increase in the peak amplitude of integrated phrenic nerve discharge lasting at least 1 h beyond the end of the infusion. The increase peaked at 90 min at 58.3 ± 5.7% above baseline. There was an associated increase in the slope of the phrenic response to increasing inspired CO(2). There was also a moderate and sustained decrease in arterial pressure 9 ± 1.3 mmHg at 120 min, with no associated change in heart rate. These data indicate that leptin elicits a sustained increase in respiratory motor output that outlasts the administration leptin via a mechanism that does not require alterations in arterial PCO(2), body temperature, or systemic afferent feedback via the vagus nerves. This stimulation may help to prevent obesity-related hypoventilation.

No MeSH data available.


Related in: MedlinePlus