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 involved in cardiovascular regulation. Sympathoadrenal hyperactivity and altered baroreflex activity have been implicated in the development of hypertension. The purpose of this investigation was to determine whether proenkephalin gene expression is altered in the arterial baroreceptor reflex region of the brain and in neurons involved in regulating sympathetic outflow, during the development of hypertension. Proenkephalin 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 plysmography. There were no differences in blood pressure at 4 weeks, however by 14 weeks resting systolic blood pressure was similar to 40% higher 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, and 55%, respectively) in the SHR at 14 weeks. However, in the locus coeruleus (LC), anterior (AH) and lateral hypothalamus (LH), proenkephalin mRNA was significantly increased (similar to 50, 100 and 100%, respectively) in the SHR. The decrease in proenkephalin mRNA in the NTS, CVLM, and RVLM may attenuate arterial baroreceptor reflex activity, while the increase in proenkephalin mRNA in the LC, AH and LH may increase sympathetic tone by inhibiting the activity of sympathodepressor preganglionic neurons in the intermediolateral cell column of the spinal cord.