CIRCADIAN REGULATION OF THE BIOSYNTHESIS OF CARDIAC MET-ENKEPHALIN AND PRECURSORS IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

Preproenkephalin A mRNA (ppEnk mRNA) and immunoreactive Metenkephalin (ir-Met-Enk) were measured in the heart of 4, 8 and 16 week-old normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. WKY rats displayed a small decrease in their cardiac concentration of free (1.3 to 1.0 pmol/g) and cryptic (enzyme processed: 5.3 to 3.7 pmol/g) ir-Met-Enk with aging while the abundance of ppEnk mRNA increased by 3.2 fold between 4 and 16 week-old animals. Similar decreases in free (1.5 to 1.0 pmol/g) and cryptic (5.6 to 4.2 pmol/g) ir-Met-Enk levels were observed in SHR with aging but the rise in the level of ppEnk mRNA was much more pronounced reaching at 16 week-old levels of 7.3 times higher than at 4 week-old and 4.3 times higher than in age-matched WKY. The lack of correlation between the concentration of free and cryptic ir-Met-Enk and the abundance of ppEnk mRNA led us to measure the level of peptides in the heart of 16 week-old animals sacrificed at 4 hr intervals over a 24 hr period. SHR rats displayed circadian variations in their heart content of free and cryptic ir-Met-Enk and increased levels (1.6 fold) of cryptic peptide as compared with WKY at the beginnings of light (6 hr) and dark (18 and 22 hr) periods, suggesting the occurrence of cyclic and transitory upregulation of cDNA transcription and/or derepression of mRNA translation.