PROENKEPHALIN GENE-EXPRESSION IS ALTERED IN THE BRAIN OF SPONTANEOUSLY HYPERTENSIVE RATS DURING THE DEVELOPMENT OF HYPERTENSION

Enkephalins have been discovered in various regions of the brain invol ved in cardiovascular regulation. Sympathoadrenal hyperactivity and al tered baroreflex activity have been implicated in the development of h ypertension. The purpose of this investigation was to determine whethe r proenkephalin gene expression is altered in the arterial barorecepto r reflex region of the brain and in neurons involved in regulating sym pathetic outflow, during the development of hypertension. Proenkephali n mRNA levels were compared, using in situ hybridization, in 4- and 14 week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Systolic blood pressure was measured by tail-cuff impedance ply smography. There were no differences in blood pressure at 4 weeks, how ever by 14 weeks resting systolic blood pressure was similar to 40% hi gher in SHR (162.5 +/- 1.6 vs. 117.3 +/- 1.5 mmHg). Proenkephalin gene expression in the nucleus tractus solitarius (NTS), caudal (CVLM) and rostral ventrolateral medulla (RVLM) was lower (similar to 67, 50, an d 55%, respectively) in the SHR at 14 weeks. However, in the locus coe ruleus (LC), anterior (AH) and lateral hypothalamus (LH), proenkephali n mRNA was significantly increased (similar to 50, 100 and 100%, respe ctively) in the SHR. The decrease in proenkephalin mRNA in the NTS, CV LM, and RVLM may attenuate arterial baroreceptor reflex activity, whil e the increase in proenkephalin mRNA in the LC, AH and LH may increase sympathetic tone by inhibiting the activity of sympathodepressor preg anglionic neurons in the intermediolateral cell column of the spinal c ord.