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Leptin into the rostral ventral lateral medulla (RVLM) augments renal sympathetic nerve activity and blood pressure.

Barnes MJ, McDougal DH - Front Neurosci (2014)

Bottom Line: While this hormone normally acts to reduce feeding behavior and increase energy expenditure, in obesity, resistance to these effects occurs even though the hormone is released in large amounts.Sympathetic control of blood pressure is maintained principally by autonomic reflex control circuits in the caudal brainstem.The rostral ventral-lateral medulla (RVLM) is the primary regulator of the sympathetic nervous system, sending excitatory fibers to sympathetic preganglionic neurons to regulate sympathetic control over resistance vessels and blood pressure.

View Article: PubMed Central - PubMed

Affiliation: Nutrition and Neural Signaling Laboratory, Pennington Biomedical Research Center Baton Rouge, LA, USA.

ABSTRACT
Leptin is a hormone released from adipose tissue. While this hormone normally acts to reduce feeding behavior and increase energy expenditure, in obesity, resistance to these effects occurs even though the hormone is released in large amounts. Although leptin no longer works to suppress feeding in the obese, leptin retains its potent effects on other autonomic functions such as blood pressure regulation. Leptin has been associated with hypertension and increased sympathetic autonomic activity. Therefore, leptin is emerging as a major contributor to the hypertensive state observed in obesity. Sympathetic control of blood pressure is maintained principally by autonomic reflex control circuits in the caudal brainstem. The rostral ventral-lateral medulla (RVLM) is the primary regulator of the sympathetic nervous system, sending excitatory fibers to sympathetic preganglionic neurons to regulate sympathetic control over resistance vessels and blood pressure. Previous studies from our laboratory have shown that neurons in the ventral lateral medulla express leptin receptors (ObRb). Our present study using pseudo-rabies multi-synaptic retrograde tract tracing and immunohistochemical methods revealed that neurons within the RVLM that send sympathetic projections to the kidney express leptin receptors. Acute microinjection of leptin (1 and 3 μg; 40 nL) into the RVLM evoked a significant increase in Mean Arterial Pressure (MAP) and renal sympathetic nerve activity (RSNA). When the 3 μg dose of leptin was preceded with a leptin antagonist, (SLAN-4; 1 ng), it attenuated the cardiovascular response of leptin. Taken together, these data suggest that leptin's actions within the RVLM may influence blood pressure and renal sympathetic nerve activity.

No MeSH data available.


Related in: MedlinePlus

Histological and physiological verification of RVLM injection site. A subset of animals received Chicago Blue injection at the end of the glutamate identification procedure to verify histological placement of pipette. Coronal sections through the hindbrain were used to identify the injection site at the level of the RVLM (A). Scale bar = 500 microns. Microinjection of glutamate (10 mM; 40 nL) into the RVLM evoked transient increase in MAP (B) and renal sympathetic nerve activity (C) within 30 s of injection. These parameters returned to baseline levels within 15 min of the injection.
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Figure 3: Histological and physiological verification of RVLM injection site. A subset of animals received Chicago Blue injection at the end of the glutamate identification procedure to verify histological placement of pipette. Coronal sections through the hindbrain were used to identify the injection site at the level of the RVLM (A). Scale bar = 500 microns. Microinjection of glutamate (10 mM; 40 nL) into the RVLM evoked transient increase in MAP (B) and renal sympathetic nerve activity (C) within 30 s of injection. These parameters returned to baseline levels within 15 min of the injection.

Mentions: RVLM neurons were identified by nano-injection of glutamate which elicited a minimum increase of 15 mmHg in blood pressure within 15 s (Figure 3) and an increase in RSNA which preceded the change in blood pressure (Figures 3B,C). The effect of glutamate on blood pressure and RSNA had a short duration; all parameters returned to baseline within 15 min. At the conclusion of the experiments, a subset of animals was injected with Chicago Blue to further verify the location of the injection site (Figure 3A).


Leptin into the rostral ventral lateral medulla (RVLM) augments renal sympathetic nerve activity and blood pressure.

Barnes MJ, McDougal DH - Front Neurosci (2014)

Histological and physiological verification of RVLM injection site. A subset of animals received Chicago Blue injection at the end of the glutamate identification procedure to verify histological placement of pipette. Coronal sections through the hindbrain were used to identify the injection site at the level of the RVLM (A). Scale bar = 500 microns. Microinjection of glutamate (10 mM; 40 nL) into the RVLM evoked transient increase in MAP (B) and renal sympathetic nerve activity (C) within 30 s of injection. These parameters returned to baseline levels within 15 min of the injection.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125949&req=5

Figure 3: Histological and physiological verification of RVLM injection site. A subset of animals received Chicago Blue injection at the end of the glutamate identification procedure to verify histological placement of pipette. Coronal sections through the hindbrain were used to identify the injection site at the level of the RVLM (A). Scale bar = 500 microns. Microinjection of glutamate (10 mM; 40 nL) into the RVLM evoked transient increase in MAP (B) and renal sympathetic nerve activity (C) within 30 s of injection. These parameters returned to baseline levels within 15 min of the injection.
Mentions: RVLM neurons were identified by nano-injection of glutamate which elicited a minimum increase of 15 mmHg in blood pressure within 15 s (Figure 3) and an increase in RSNA which preceded the change in blood pressure (Figures 3B,C). The effect of glutamate on blood pressure and RSNA had a short duration; all parameters returned to baseline within 15 min. At the conclusion of the experiments, a subset of animals was injected with Chicago Blue to further verify the location of the injection site (Figure 3A).

Bottom Line: While this hormone normally acts to reduce feeding behavior and increase energy expenditure, in obesity, resistance to these effects occurs even though the hormone is released in large amounts.Sympathetic control of blood pressure is maintained principally by autonomic reflex control circuits in the caudal brainstem.The rostral ventral-lateral medulla (RVLM) is the primary regulator of the sympathetic nervous system, sending excitatory fibers to sympathetic preganglionic neurons to regulate sympathetic control over resistance vessels and blood pressure.

View Article: PubMed Central - PubMed

Affiliation: Nutrition and Neural Signaling Laboratory, Pennington Biomedical Research Center Baton Rouge, LA, USA.

ABSTRACT
Leptin is a hormone released from adipose tissue. While this hormone normally acts to reduce feeding behavior and increase energy expenditure, in obesity, resistance to these effects occurs even though the hormone is released in large amounts. Although leptin no longer works to suppress feeding in the obese, leptin retains its potent effects on other autonomic functions such as blood pressure regulation. Leptin has been associated with hypertension and increased sympathetic autonomic activity. Therefore, leptin is emerging as a major contributor to the hypertensive state observed in obesity. Sympathetic control of blood pressure is maintained principally by autonomic reflex control circuits in the caudal brainstem. The rostral ventral-lateral medulla (RVLM) is the primary regulator of the sympathetic nervous system, sending excitatory fibers to sympathetic preganglionic neurons to regulate sympathetic control over resistance vessels and blood pressure. Previous studies from our laboratory have shown that neurons in the ventral lateral medulla express leptin receptors (ObRb). Our present study using pseudo-rabies multi-synaptic retrograde tract tracing and immunohistochemical methods revealed that neurons within the RVLM that send sympathetic projections to the kidney express leptin receptors. Acute microinjection of leptin (1 and 3 μg; 40 nL) into the RVLM evoked a significant increase in Mean Arterial Pressure (MAP) and renal sympathetic nerve activity (RSNA). When the 3 μg dose of leptin was preceded with a leptin antagonist, (SLAN-4; 1 ng), it attenuated the cardiovascular response of leptin. Taken together, these data suggest that leptin's actions within the RVLM may influence blood pressure and renal sympathetic nerve activity.

No MeSH data available.


Related in: MedlinePlus