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Neural mechanisms and transmitters

Nerve Growth Factor Enhances Calcitonin Gene-Related Peptide Expression in the Spontaneously Hypertensive Rat

M Huawei Zhao, M Scott C Supowit, M Donald J DiPette
https://doi.org/10.1161/01.HYP.36.Suppl_1.701-a
Hypertension. 2000;36:701
M Huawei Zhao
Michigan State Univ, East Lansing, MI
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M Scott C Supowit
Michigan State Univ, East Lansing, MI
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M Donald J DiPette
Michigan State Univ, East Lansing, MI
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Abstract

P45

We previously reported that there is a marked decrease in neuronal (dorsal root ganglia [DRG] sensory neurons) CGRP expression in the SHR compared to WKY controls. This reduction in such a potent vasodilator could contribute to the elevated BP. We hypothesize that administration of NGF, a potent in vivo stimulator of CGRP expression, to SHR would decrease the BP. NGF (10 nM/kg/day, i.p.) was given to 12 week SHR (n=8-11/group) once a day for 1, 3, and 7 days. Control SHR received vehicle only. All rats were instrumented for CGRP receptor antagonist (CGRP8-37) administration (i.v.) and continuous MAP (arterial) recording and were studied in a concious and unrestrained state. Both the 1 and 3 day NGF treatments lowered the MAP (147±5 and 147±3 mmHg; respectively, p<0.05) compared to the controls (166±3 mmHg). However, by day 7 the MAP had returned to control levels (169±5 mmHg). To determine whether CGRP was involved in the BP lowering response to NGF, saline or CGRP8-37 (bolus dose of 200 μg) were administered i.v. to all rats. Saline was without effect in any of the groups studied. In contrast, CGRP8-37administration produced a significant increase in MAP in both the 1 (13±1 mmHg) and 3 (10±1 mmHg) day NGF treatment groups. Surprisingly, in the 7 day treatment group, CGRP8-37 also increased the MAP (13±2 mmHg) despite the baseline BP being back up to control levels. Quantification of CGRP mRNA and peptide levels in DRG revealed a significant (p<0.05) 1.5-fold increase on days 1 and 3 and a 1.75-fold increase on day 7. These data demonstrate that NGF treatment of SHR can significantly increase neuronal CGRP expression. At days 1 and 3, NGF produces a marked depressor response that is primarily due to CGRP as evidenced by the pressor effect of CGRP8-37. In the day 7 group, CGRP also plays a counterregulatory role even though the MAP has returned to control levels. This may result from an NGF-mediated upregulation of a pressor system that counteracts the hypotensive actions of CGRP. These results, therefore, suggest that the decreased production of CGRP in the SHR could contribute to the elevated BP observed in this hypertensive model.

  • Gene expression, Hypertension
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October 2000, Volume 36, Issue Suppl 1
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    Nerve Growth Factor Enhances Calcitonin Gene-Related Peptide Expression in the Spontaneously Hypertensive Rat
    M Huawei Zhao, M Scott C Supowit and M Donald J DiPette
    Hypertension. 2000;36:701, originally published October 1, 2000
    https://doi.org/10.1161/01.HYP.36.Suppl_1.701-a

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    Nerve Growth Factor Enhances Calcitonin Gene-Related Peptide Expression in the Spontaneously Hypertensive Rat
    M Huawei Zhao, M Scott C Supowit and M Donald J DiPette
    Hypertension. 2000;36:701, originally published October 1, 2000
    https://doi.org/10.1161/01.HYP.36.Suppl_1.701-a
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