Abstract
Following binding to receptors in the arcuate nucleus (ArcN), insulin increases sympathetic nerve activity (SNA) and baroreflex control of SNA via a pathway that includes the paraventricular nucleus of the hypothalamus (PVN). Previous studies in males indicate that the sympathoexcitatory response is mediated by α-melanocyte stimulating hormone (α -MSH), which binds to PVN melanocortin type 3/4 receptors (MC3/4R). The present study was conducted in α-chloralose-anesthetized female rats to test the hypothesis that suppression of inhibitory neuropeptide Y (NPY) inputs to the PVN is also involved. In support of this, blockade of PVN NPY Y1 receptors with BIBO 3304 (NPY1x), ArcN insulin nanoinjections, and PVN NPY1x followed by ArcN insulin each increased lumbar SNA (LSNA) and its baroreflex regulation similarly. Moreover, prior PVN injections of NPY blocked the sympathoexcitatory effects of ArcN insulin. Finally, PVN nanoinjections of the MC3/4R inhibitor SHU9119 prevented both the acute (15 min) and longer, more slowly developing (60 min), increases in LSNA in response to ArcN insulin. In conclusion, in females, ArcN insulin increases LSNA, in part, by suppressing tonic PVN NPY inhibition, which unmasks excitatory α-MSH drive of LSNA. Moreover, the steadily increasing rise in LSNA induced by ArcN insulin is also dependent on PVN MC3/4R.
| Original language | English (US) |
|---|---|
| Pages (from-to) | R97-R103 |
| Journal | American Journal of Physiology - Regulatory Integrative and Comparative Physiology |
| Volume | 311 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 1 2016 |
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Keywords
- Arcuate nucleus
- NPY
- PVN
- SNA
- α-MSH
ASJC Scopus subject areas
- Physiology
- Medicine(all)
- Physiology (medical)
Cite this
Insulin increases sympathetic nerve activity in part by suppression of tonic inhibitory neuropeptide y inputs into the paraventricular nucleus in female rats. / Cassaglia, Priscila A.; Shi, Zhigang; Brooks, Virginia.
In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 311, No. 1, 01.07.2016, p. R97-R103.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Insulin increases sympathetic nerve activity in part by suppression of tonic inhibitory neuropeptide y inputs into the paraventricular nucleus in female rats
AU - Cassaglia, Priscila A.
AU - Shi, Zhigang
AU - Brooks, Virginia
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Following binding to receptors in the arcuate nucleus (ArcN), insulin increases sympathetic nerve activity (SNA) and baroreflex control of SNA via a pathway that includes the paraventricular nucleus of the hypothalamus (PVN). Previous studies in males indicate that the sympathoexcitatory response is mediated by α-melanocyte stimulating hormone (α -MSH), which binds to PVN melanocortin type 3/4 receptors (MC3/4R). The present study was conducted in α-chloralose-anesthetized female rats to test the hypothesis that suppression of inhibitory neuropeptide Y (NPY) inputs to the PVN is also involved. In support of this, blockade of PVN NPY Y1 receptors with BIBO 3304 (NPY1x), ArcN insulin nanoinjections, and PVN NPY1x followed by ArcN insulin each increased lumbar SNA (LSNA) and its baroreflex regulation similarly. Moreover, prior PVN injections of NPY blocked the sympathoexcitatory effects of ArcN insulin. Finally, PVN nanoinjections of the MC3/4R inhibitor SHU9119 prevented both the acute (15 min) and longer, more slowly developing (60 min), increases in LSNA in response to ArcN insulin. In conclusion, in females, ArcN insulin increases LSNA, in part, by suppressing tonic PVN NPY inhibition, which unmasks excitatory α-MSH drive of LSNA. Moreover, the steadily increasing rise in LSNA induced by ArcN insulin is also dependent on PVN MC3/4R.
AB - Following binding to receptors in the arcuate nucleus (ArcN), insulin increases sympathetic nerve activity (SNA) and baroreflex control of SNA via a pathway that includes the paraventricular nucleus of the hypothalamus (PVN). Previous studies in males indicate that the sympathoexcitatory response is mediated by α-melanocyte stimulating hormone (α -MSH), which binds to PVN melanocortin type 3/4 receptors (MC3/4R). The present study was conducted in α-chloralose-anesthetized female rats to test the hypothesis that suppression of inhibitory neuropeptide Y (NPY) inputs to the PVN is also involved. In support of this, blockade of PVN NPY Y1 receptors with BIBO 3304 (NPY1x), ArcN insulin nanoinjections, and PVN NPY1x followed by ArcN insulin each increased lumbar SNA (LSNA) and its baroreflex regulation similarly. Moreover, prior PVN injections of NPY blocked the sympathoexcitatory effects of ArcN insulin. Finally, PVN nanoinjections of the MC3/4R inhibitor SHU9119 prevented both the acute (15 min) and longer, more slowly developing (60 min), increases in LSNA in response to ArcN insulin. In conclusion, in females, ArcN insulin increases LSNA, in part, by suppressing tonic PVN NPY inhibition, which unmasks excitatory α-MSH drive of LSNA. Moreover, the steadily increasing rise in LSNA induced by ArcN insulin is also dependent on PVN MC3/4R.
KW - Arcuate nucleus
KW - NPY
KW - PVN
KW - SNA
KW - α-MSH
UR - http://www.scopus.com/inward/record.url?scp=84984595869&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84984595869&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00054.2016.
DO - 10.1152/ajpregu.00054.2016.
M3 - Article
VL - 311
SP - R97-R103
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 1
ER -