P-440: Attenuated renal sympathetic nerve responses to stimulation of melanocortin system in absence of leptin receptors

Kamal Rahmouni; William G Haynes; Donald A Morgan; Allyn L Mark

doi:10.1016/S0895-7061(02)02791-7

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P-440: Attenuated renal sympathetic nerve responses to stimulation of melanocortin system in absence of leptin receptors

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P-440: Attenuated renal sympathetic nerve responses to stimulation of melanocortin system in absence of leptin receptors

Kamal Rahmouni, William G Haynes, Donald A Morgan and Allyn L Mark

American journal of hypertension, Vol.15(S3), pp.191A-191A

04/2002

DOI: 10.1016/S0895-7061(02)02791-7

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Abstract

We have previously shown the importance of melanocortin-4 receptors in the control of renal sympathetic nerve outflow by leptin. The sympathoexcitatory effect of leptin was absent in melanocortin-4 receptor knockout mice. Here we examine whether absence of leptin receptors (in db/db mice) alters sympathetic response to melanocortin-4 receptor stimulation. Each mouse received an intracerebroventricular (icv) cannula one week before the study. Arterial pressure, heart rate and renal sympathetic nerve activity (RSNA) were recorded under anesthesia (Xylaxine/Ketamine) at baseline and during 4 hours after icv injection. The effects of icv administration of leptin and melanocortin-4 receptor agonist (MTII) were compared in leptin deficient (db/db) mice and their wild-type controls (C57BL/KsJ). At baseline, mean arterial pressure and RSNA were higher (P=0.0005 and P<0.0001, respectively) in the db/db mice (91+/-1 mmHg and 1.8+/-0.1 volts*sec/min, n=48) as compared to their littermate controls (84+/-1, 1.3+/-0.03, n=49). As expected, icv administration of leptin (2 mcg) increased RSNA by 297+/-97% (n=7, P<0.01) in wild-type mice, but leptin did not affect RSNA in the db/db mice (n=5). ICV injection of melanocortin-4 receptor agonist MTII (2 mcg) increased RSNA in the wild-type mice by 291+/-67% (n=7, P<0.001) but not in the db/db mice. A ten fold higher dose (20 mcg) of MTII was required to increase RSNA (170+/-40%, n=7, P+/-0.01) in db/db mice. In contrast, the rise in RSNA induced by icv insulin (20 mcU) was of the same magnitude in the wild-type controls (157+/-39%, n=6, P<0.01) and db/db mice (142+/-15%, n=6, P<0.01). Our data demonstrate that in absence of leptin receptors the sympathoexcitatory effects of melanocortin-4 receptor stimulation are attenuated. These findings confirm an important physiologic interaction of leptin and melanocortin system in regulation of sympathetic nerve activity.

Melanocortin System

Leptin

Sympathetic Nerve Activity

Details

Title: Subtitle: P-440: Attenuated renal sympathetic nerve responses to stimulation of melanocortin system in absence of leptin receptors
Creators: Kamal Rahmouni - Hypertension Genetics SCOR and Internal Medicine, University of Iowa and VAMC, Iowa City, IA, United States
William G Haynes - Hypertension Genetics SCOR and Internal Medicine, University of Iowa and VAMC, Iowa City, IA, United States
Donald A Morgan - Hypertension Genetics SCOR and Internal Medicine, University of Iowa and VAMC, Iowa City, IA, United States
Allyn L Mark - Hypertension Genetics SCOR and Internal Medicine, University of Iowa and VAMC, Iowa City, IA, United States
Resource Type: Journal article
Publication Details: American journal of hypertension, Vol.15(S3), pp.191A-191A
DOI: 10.1016/S0895-7061(02)02791-7
ISSN: 0895-7061
eISSN: 1879-1905
Publisher: Oxford University Press
Language: English
Date published: 04/2002
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984072095802771

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