Original Article

Mapping of preproenkephalin mRNA in brain of spontaneously hypertensive rats

Xia Yin, Yan-Hua Zhu, Shao-Fen Xu


To detect different expression of preproenkephalin mRNA (PPE mRNA) in 16-wk-old spontaneously hypertensive rat (SHR) and age-matched normotensive Wistar-Kyoto rat (WKY).

Nonradioactive in situ hybridization was performed using digoxigenin-labeled RNA probe.

Compared with WKY rats, PPE mRNA levels of 16-wk-old SHR increased in hypothalamic nuclei (> 20), amygdaloid nuclei (> 23), ventrolateral central gray (21.2), reticular substantia nigra (21.5), interpeduncular nuclei (> 21), nucleus of the solitary tract (30.7), rostroventrolateral reticular nucleus (29.1), gigantocellular reticular nucleus (23.9) and thoracic spinal cord (> 30); decreased in dorsal central gray (22.7). No difference was found in compact substantia nigra (22.8), dentate gyrus (26.2) and CA1, CA2, CA3 of hippocampus (> 25).

PPE mRNA in brain regions involved in modulation of blood pressure may be associated with the genesis of spontaneous hypertension in SHR. Enkephalin, an endogenous ligand of opioid receptors, is important in the regulation of blood pressure (BP). Intracerebroventricular injection (icv) of mu agonist [D-Ala2-MePhe4-Gly5-ol]-enkephalin (DAGO) and delta agonist [D-Ala2, D-Leu5]-enkephalin (DADLE) increased the BP[1]. In situ hybridization study showed preproenkephalin mRNA was localized in hypothalamic nuclei, hippocampus, NTS, and spinal cord[2], where the cardiovascular regulation took place. The icv of mu agonist morphiceptin induced a pressor response in SHR but hypotension in WKY rat, and delta agonist Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET) icv decreased BP in SHR but increased BP in WKY[3]. Compared with WKY rats, SHR had greater concentration of methionine-enkephalin (Met-Enk) in cortex, pons, and medulla[4], but lower Leu-Enk in suprachiasmatic nucleus[5]. These studies imply that opiate system is disturbed in essential hypertension. The aim of this study is to determine whether the biosynthetic activity of CNS opiates in brain is altered in case of essential hypertension.

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