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Horm Metab Res 2015; 47(02): 125-132
DOI: 10.1055/s-0034-1375689
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Cerebral Klotho Protein as a Humoral Factor for Maintenance of Baroreflex

L.-J. Chen   *
1   Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
,
M.-F. Cheng   *
2   Division of Nephrology, Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
,
P.-M. Ku
3   Department of Cardiology, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan
,
J.-T. Cheng
1   Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
4   Institute of Medical Sciences, Chang Jung Christian University, Guiren, Tainan City, Taiwan
› Author Affiliations
Further Information

Publication History

received 21 December 2013

accepted 24 April 2014

Publication Date:
27 May 2014 (online)

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Abstract

The klotho protein produced by the choroid plexus is known as a humoral factor in central nervous system. Many hormones affecting the baroreflex sensitivity have been introduced in the brain. However, role of klotho in the baroreflex sensitivity is still unknown. Recently, mutations in the klotho gene have been linked to cardiovascular diseases in both animals and human subjects. Also, silencing of brain klotho has been reported to enhance cold-induced elevation of blood pressure. Thus, we investigated the role of klotho in maintenance of central cardiovascular reflex sensitivity. Male Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were used. Either klotho shRNA or scramble shRNA was also ICV-infused into the brains of WKY rats to investigate the role of klotho in brain. Recombinant klotho or rat IgG was infused into the cerebral paraventricle (ICV) of SHRs for further understanding the role of klotho in hypertension. The baroreflex sensitivity was detected using the challenge with a depressor dose of sodium nitroprusside (SNP, 50 μg/kg) or with a pressor dose of phenylephrine (PE, 8 μg/kg). We found that silencing of klotho expression in the brain decreased the baroreflex sensitivity in WKY rats. Also, modulation of the blood pressure for one week altered the cardiovascular homeostasis and resulted in an increased expression of klotho in medulla oblongata. Moreover, the baroreflex sensitivity was restored in SHRs that received recombinant klotho through ICV brain. Thus, klotho is involved in the maintenance of baroreflex sensitivity in the brain.

Key words

klotho - baroreflex sensitivity - klotho shRNA - SHR - ICV injection

* Contributed equally to this study.


 

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