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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

Dual localization of leptin receptors (ObRb; red) and pseudo rabies virus infected cells (PRV; green) resulting from renal PRV injection. (A) Is a low power montage of the complete ventral half of the medulla at the level of the RVLM. (B–D) Are high magnification of cell cluster in left RVLM shown in (A) demonstrating PRV positive RVLM neurons (B), ObRb expressing RVLM neurons (C), and double labeled RVLM neurons (D). Scale bar = 100 microns.
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Figure 2: Dual localization of leptin receptors (ObRb; red) and pseudo rabies virus infected cells (PRV; green) resulting from renal PRV injection. (A) Is a low power montage of the complete ventral half of the medulla at the level of the RVLM. (B–D) Are high magnification of cell cluster in left RVLM shown in (A) demonstrating PRV positive RVLM neurons (B), ObRb expressing RVLM neurons (C), and double labeled RVLM neurons (D). Scale bar = 100 microns.

Mentions: Cells in the ventral hindbrain that were positive for ObRb staining (i.e., expressed leptin receptors) were localized in one of four regions: the C1/A1 cell column, ventromedial medulla (VMM), caudal raphe, and A5 cell group. The ObRb staining in the C1/A1, caudal raphe, and A5 was quite distinct and easily assigned to these medullary nuclei based on Paxinos and Watson (2007) (Figure 1). In contrast, the staining in the VMM was diffuse and often overlapped adjacent nuclei such as the paragigantocellular nuclear subdivisions, the reticular nucleus subdivisions, and the inferior olive (Figure 2A). ObRb positive cells (ObRb+) were defined as those cells which displayed extensive cytoplasmic ObRb staining (see insets of Figures 1, 2C), as opposed to cells which merely displayed isolated ObRb punctate staining. An average of 420 ± 87 ObRb+ cells were observed in C1/A1, 146 ± 32 ObRb+ cells were observed in VMM, 107 ± 87 ObRb+ cells were observed in A5, and 26 ± 14 ObRb+ cells were observed in the caudal raphe (Table 1).


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

Barnes MJ, McDougal DH - Front Neurosci (2014)

Dual localization of leptin receptors (ObRb; red) and pseudo rabies virus infected cells (PRV; green) resulting from renal PRV injection. (A) Is a low power montage of the complete ventral half of the medulla at the level of the RVLM. (B–D) Are high magnification of cell cluster in left RVLM shown in (A) demonstrating PRV positive RVLM neurons (B), ObRb expressing RVLM neurons (C), and double labeled RVLM neurons (D). Scale bar = 100 microns.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Dual localization of leptin receptors (ObRb; red) and pseudo rabies virus infected cells (PRV; green) resulting from renal PRV injection. (A) Is a low power montage of the complete ventral half of the medulla at the level of the RVLM. (B–D) Are high magnification of cell cluster in left RVLM shown in (A) demonstrating PRV positive RVLM neurons (B), ObRb expressing RVLM neurons (C), and double labeled RVLM neurons (D). Scale bar = 100 microns.
Mentions: Cells in the ventral hindbrain that were positive for ObRb staining (i.e., expressed leptin receptors) were localized in one of four regions: the C1/A1 cell column, ventromedial medulla (VMM), caudal raphe, and A5 cell group. The ObRb staining in the C1/A1, caudal raphe, and A5 was quite distinct and easily assigned to these medullary nuclei based on Paxinos and Watson (2007) (Figure 1). In contrast, the staining in the VMM was diffuse and often overlapped adjacent nuclei such as the paragigantocellular nuclear subdivisions, the reticular nucleus subdivisions, and the inferior olive (Figure 2A). ObRb positive cells (ObRb+) were defined as those cells which displayed extensive cytoplasmic ObRb staining (see insets of Figures 1, 2C), as opposed to cells which merely displayed isolated ObRb punctate staining. An average of 420 ± 87 ObRb+ cells were observed in C1/A1, 146 ± 32 ObRb+ cells were observed in VMM, 107 ± 87 ObRb+ cells were observed in A5, and 26 ± 14 ObRb+ cells were observed in the caudal raphe (Table 1).

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