Limits...
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

Mean arterial pressure and heart rate 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 decrease in arterial pressure, *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3569609&req=5

Figure 4: Mean arterial pressure and heart rate 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 decrease in arterial pressure, *p < 0.05.

Mentions: Leptin treatment elicited a progressive decrease in MAP over the 120 min following the initiation of leptin administration. At 120 min, MAP had decreased 10 ± 1.3 mmHg from a control of 79 ± 4.1 mmHg (Figures 1, 4; p < 0.05). Both systolic and diastolic pressures exhibited similar decreases. There was no significant change in MAP of control animals; compared to an initial value of 86 ± 4.3 mmHg, MAP was 84 ± 4.9 mmHg at 90 min, (n = 4) and in the two rats measured at 120 min it was 87 ± 1.0 mmHg (Figures 1, 4). Despite the decrease in MAP in leptin treated rats, there was no change in heart rate over the course of the experiment in either the leptin or control group of animals (Figures 1, 4).


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)

Mean arterial pressure and heart rate 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 decrease in arterial pressure, *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Mean arterial pressure and heart rate 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 decrease in arterial pressure, *p < 0.05.
Mentions: Leptin treatment elicited a progressive decrease in MAP over the 120 min following the initiation of leptin administration. At 120 min, MAP had decreased 10 ± 1.3 mmHg from a control of 79 ± 4.1 mmHg (Figures 1, 4; p < 0.05). Both systolic and diastolic pressures exhibited similar decreases. There was no significant change in MAP of control animals; compared to an initial value of 86 ± 4.3 mmHg, MAP was 84 ± 4.9 mmHg at 90 min, (n = 4) and in the two rats measured at 120 min it was 87 ± 1.0 mmHg (Figures 1, 4). Despite the decrease in MAP in leptin treated rats, there was no change in heart rate over the course of the experiment in either the leptin or control group of animals (Figures 1, 4).

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