Proceedings of The Physiological Society

University College Cork (2004) J Physiol 560P, PC6



Waki,Hidefumi ; Kasparov,Sergey ; Miyake,Masao ; Katahira,Kiyoaki ; Liu,Beihul ; Murphy,David ; Paton,Julian FR;

1. Physiology, Bristol University, Bristol, United Kingdom. 2. Physiology, Fukushima Medical University School of Medicine, Fukushima , Japan. 3. Experimental Animal Center, Fukushima Medical University School of Medicine, Fukushima , Japan. 4. Henry Wellcome Laboratories for Integrative Neurosciences and Endocrinology, Bristol University, Bristol, United Kingdom.

Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. Since the nucleus tractus solitarii (NTS) is a pivotal region regulating both baroreceptor reflex function and set-point control of arterial pressure, it may be a participating central nervous site for causing primary hypertension. In this study, we performed cDNA microarray analysis to screen for differentially expressed genes in the NTS between spontaneously hypertensive rats (SHR), which is a well-known animal model for hypertension, and their progenitor, Wistar-Kyoto rats (WKY). Three week old and 18-week-old male rats were humanely killed by cervical dislocation and the caudal extent of the NTS was micro-dissected out from each animal. Total RNA was extracted and fluorescently labeled cDNA array probes were synthesized using CY-3 as a marker for SHR and CY-5 for WKY. The SHR and WKY probes were mixed and hybridized to a rat cDNA array (Agilent Technologies), representing 14,815 genes. The level of signal in each array was compared between SHR and WKY. Signals exhibiting a >2 difference between these strains were validated using real-time RT-PCR. 22 genes showed a greater expression in young (pre-hypertensive) and adult (hypertensive) SHR relative to WKY, whereas two other genes were down-regulated. So far our validation using real-time PCR has confirmed that junctional adhesion molecule-1 (JAM-1) is highly expressed in both pre-hypertensive (n=4) and hypertensive SHRs (n=6) compared to WKY (young, n=4; adult, n=6). These data suggest that some endothelium-related genes within NTS are differentially expressed between SHR and WKY and that these differences are not secondary to the hypertension. Functional contribution of JAM-1 to blood pressure phenotypes of the SHR and WKY is currently under investigation.

Where applicable, experiments conform with Society ethical requirements