Specific inflammatory condition in nucleus tractus solitarii of the SHR: novel insight for neurogenic hypertension?
Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. Since the brainstem structure--the nucleus of the solitary tract (NTS)--is a pivotal region for regulating the set-point of arterial pressure, we proposed a role for it in the development of primary hypertension. Using microarray and real-time RT-PCR, we have recently identified that some pro-inflammatory molecules, such as junctional adhesion molecule-1 (JAM-1; a leukocyte/platelet adhesion molecule), were over expressed in endothelial cells in the NTS of an animal model of human essential hypertension--the spontaneously hypertensive rat (SHR) compared to normotensive Wistar Kyoto rats (WKY). Adenoviral mediated over expression of JAM-1 in NTS of WKY rats produced both hypertension and localized leukocyte adherence to the microvasculature. With a known effect of leukocyte adhesion causing cytokine release, we predicted differences in the level of gene expression of cytokines in the NTS of SHR relative to WKY. Gene expression of monocyte chemoattractant protein-1 (MCP-1) was higher in the NTS of SHR while inter-leukin-6 (IL-6) was lower in the NTS of SHR compared to the WKY. Because both inflammatory molecules are known to affect neural functions, our data suggest that the microvasculature of NTS of the SHR exhibits a specific inflammatory state. We propose a new hypothesis that as a consequence of enhanced expression of leukocyte adhesion molecules within the microvasculature of NTS there is a specific inflammatory response that leads to cardiovascular autonomic dysfunction contributing to neurogenic hypertension.
Waki
Hidefumi
H
Department of Physiology, Wakayama Medical University School of Medicine, 811-1, Kimiidera, Wakayama 641-8509, Japan. h-waki@wakayama-med.ac.jp
Gouraud
Sabine S
SS
Maeda
Masanobu
M
Paton
Julian F R
JF
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000235:genetics; D004195:Disease Models, Animal; D004660:Encephalitis / Q000276:immunology*; D006801:Humans; D006973:Hypertension / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D017552:Solitary Nucleus / Q000276:immunology*
C491766:Ccl2 protein, rat; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; C520495:F11r protein, rat; D015850:Interleukin-6