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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

Nano-injection of rat superactive leptin antagonist (SLAN-4) attenuated the leptin-induced increase in MAP and RSNA and decreased basal RSNA. Time course response of MAP after administering leptin and SLAN-4 into the RVLM is presented in (A). 12 min following the second injection, MAP was increased following saline + leptin relative to saline + saline controls, while saline + SLAN-4 and SLAN-4 + leptin treatment did not significantly alter MAP relative to saline + saline treatment (B). In contrast, saline + leptin treatment caused a significant increase in RNSA, while saline + SLAN-4 and SLAN-4 + leptin treatment caused a significant decrease in RNSA relative to saline + saline controls. (C) (Bonferroni t-tests; *p < 0.05).
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Figure 5: Nano-injection of rat superactive leptin antagonist (SLAN-4) attenuated the leptin-induced increase in MAP and RSNA and decreased basal RSNA. Time course response of MAP after administering leptin and SLAN-4 into the RVLM is presented in (A). 12 min following the second injection, MAP was increased following saline + leptin relative to saline + saline controls, while saline + SLAN-4 and SLAN-4 + leptin treatment did not significantly alter MAP relative to saline + saline treatment (B). In contrast, saline + leptin treatment caused a significant increase in RNSA, while saline + SLAN-4 and SLAN-4 + leptin treatment caused a significant decrease in RNSA relative to saline + saline controls. (C) (Bonferroni t-tests; *p < 0.05).

Mentions: The role of leptin receptors within the RVLM as it relates to cardiovascular parameters was assessed using the rat superactive leptin antagonist, SLAN-4. The time course response of MAP after administering leptin and SLAN-4 into the RVLM is presented in Figure 5A. A One-Way ANOVA of peak responses measured at 12 min following the second injection demonstrated a statistically significant effect of treatment [F(3, 16) = 16.64; p < 0.05]. Leptin (3 μg) administration resulted in a 7.6 ± 2.1% increase in MAP while SLAN-4 alone resulted in a 3.6 ± 0.8% decrease at the same time point. When SLAN-4 was administered into the RVLM prior to leptin (3 μg), leptin administration failed to produce an increase in MAP, and a decrease of 3.2 ± 0.6% was observed. 12 min following the second injection, the MAP responses to leptin (3 μg) alone was significantly different from the response to saline, SLAN-4, and SLAN-4 plus leptin (3 μg). The MAP response to SLAN-4 alone and SLAN-4 plus leptin (3 μg) were not significantly different from saline (Bonferroni post-hoc t-tests; p < 0.05) (Figure 5B). A One-Way ANOVA of percent change in RNSA across treatment was statistically significant [F(3, 19) = 8.288; p < 0.05]. Following saline injection, leptin (3 μg) administration resulted in a 34% increase in RNSA while SLAN-4 resulted in a 20% decrease. When SLAN-4 was administered into the RVLM prior to leptin (3 μg), a 13% decrease in RNSA was observed. The change in RNSA in response to leptin (3 μg), SLAN-4, and SLAN-4 plus leptin (3 μg), were all significantly different from saline control injections (Bonferroni post-hoc t-tests; p < 0.05) (Figure 5C).


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

Barnes MJ, McDougal DH - Front Neurosci (2014)

Nano-injection of rat superactive leptin antagonist (SLAN-4) attenuated the leptin-induced increase in MAP and RSNA and decreased basal RSNA. Time course response of MAP after administering leptin and SLAN-4 into the RVLM is presented in (A). 12 min following the second injection, MAP was increased following saline + leptin relative to saline + saline controls, while saline + SLAN-4 and SLAN-4 + leptin treatment did not significantly alter MAP relative to saline + saline treatment (B). In contrast, saline + leptin treatment caused a significant increase in RNSA, while saline + SLAN-4 and SLAN-4 + leptin treatment caused a significant decrease in RNSA relative to saline + saline controls. (C) (Bonferroni t-tests; *p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Nano-injection of rat superactive leptin antagonist (SLAN-4) attenuated the leptin-induced increase in MAP and RSNA and decreased basal RSNA. Time course response of MAP after administering leptin and SLAN-4 into the RVLM is presented in (A). 12 min following the second injection, MAP was increased following saline + leptin relative to saline + saline controls, while saline + SLAN-4 and SLAN-4 + leptin treatment did not significantly alter MAP relative to saline + saline treatment (B). In contrast, saline + leptin treatment caused a significant increase in RNSA, while saline + SLAN-4 and SLAN-4 + leptin treatment caused a significant decrease in RNSA relative to saline + saline controls. (C) (Bonferroni t-tests; *p < 0.05).
Mentions: The role of leptin receptors within the RVLM as it relates to cardiovascular parameters was assessed using the rat superactive leptin antagonist, SLAN-4. The time course response of MAP after administering leptin and SLAN-4 into the RVLM is presented in Figure 5A. A One-Way ANOVA of peak responses measured at 12 min following the second injection demonstrated a statistically significant effect of treatment [F(3, 16) = 16.64; p < 0.05]. Leptin (3 μg) administration resulted in a 7.6 ± 2.1% increase in MAP while SLAN-4 alone resulted in a 3.6 ± 0.8% decrease at the same time point. When SLAN-4 was administered into the RVLM prior to leptin (3 μg), leptin administration failed to produce an increase in MAP, and a decrease of 3.2 ± 0.6% was observed. 12 min following the second injection, the MAP responses to leptin (3 μg) alone was significantly different from the response to saline, SLAN-4, and SLAN-4 plus leptin (3 μg). The MAP response to SLAN-4 alone and SLAN-4 plus leptin (3 μg) were not significantly different from saline (Bonferroni post-hoc t-tests; p < 0.05) (Figure 5B). A One-Way ANOVA of percent change in RNSA across treatment was statistically significant [F(3, 19) = 8.288; p < 0.05]. Following saline injection, leptin (3 μg) administration resulted in a 34% increase in RNSA while SLAN-4 resulted in a 20% decrease. When SLAN-4 was administered into the RVLM prior to leptin (3 μg), a 13% decrease in RNSA was observed. The change in RNSA in response to leptin (3 μg), SLAN-4, and SLAN-4 plus leptin (3 μg), were all significantly different from saline control injections (Bonferroni post-hoc t-tests; p < 0.05) (Figure 5C).

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