AGE-ASSOCIATED INCREASE IN RAT CARDIAC OPIOID PRODUCTION

Several lines of evidence suggest that opioid peptide production in th e heart may increase during aging from adulthood through senescence. W e tested the hypothesis that cardiac opioid peptides and preproenkepha lin (PNK) mRNA would increase with advancing age. Ventricles and atria from male Wistar rats, aged 2, 6, 18, and 22-24 mo of age, were acid extracted and assayed for methionine enkephalin (ME) and leucine enkep halin (LE). Total RNA was extracted from hearts of age-matched rats an d probed for PNK mRNA by Northern blot analysis using a cDNA probe. ME and LE peptides were significantly elevated with advancing age in bot h ventricles [P < 0.001; by analysis of variance (ANOVA)]. Ventricular ME concentration exhibited a biphasic increase with approximately two fold higher peaks at 6 and 22-24 mo of age compared with the 2 mo valu e of 1.04 +/- 0.05 (SE) pmol/g wet wt. In contrast, ventricular LE con centration was largely unchanged until 22-24 mo of age when it increas ed approximately threefold over the 2-mo value of 2.19 +/- 0.14 pmol/g wet wt. Left ventricular PNK mRNA increased approximately fivefold be tween 2 and 18 mo of age (P < 0.01; ANOVA). Thus both enkephalins and the mRNA coding for them were increased in hearts of older vs. younger rats. Because opioid receptor stimulation can negatively modulate sev eral characteristics of cardiac myocyte contraction, these results may have important functional implications for the senescent heart.