Decreased expression of nitric oxide synthase in the colonic myenteric plexus of aged rats

Nitric oxide (NO) is a major non-adrenergic, non-cholinergic (NANC) inhibit ory neurotransmitter in the gastrointestinal tract. NO released from the my enteric plexus enhances colonic transit and facilitates propulsion of the c olonic contents by mediating descending relaxation. Although it has been su ggested that colonic transit delays with aging, the mechanism of delayed co lonic transit in aging remains unclear. We hypothesized that advanced age i s associated with decreased expression of neuronal NO synthase (nNOS) and c oncomitant reduction in synthesis of NO in the rat colon. We studied nNOS m RNA expression, nNOS-immunohistochemistry, nNOS-immunoblotting and NOS cata lytic activity in the mid-colon obtained from young (age 4-8 months) and ag ed (age 22-28 months) Fisher (F344 X BN)F1 rats. Western blot analysis of P GP 9.5, a generic neuronal marker, of the colonic tissues were employed to study whether the total number of neurons of the myenteric plexus is reduce d with aging. The number of nNOS-immunoreactive cells and nNOS synthesis in the colonic myenteric plexus were significantly reduced in aged rats. In c ontrast, expression of PGP 9.5 in colonic tissues was not affected in aged rats. Northern blot analysis demonstrated that the expression of neuronal n NOS mRNA was significantly reduced in the colonic tissues in aged rats. Bas al and veratridine-induced release of L-[H-3]citrulline were significantly decreased in colonic tissues from aged rats, compared to young rats. It is suggested that advanced age is associated with diminished gene expression o f nNOS, nNOS synthesis and catalytic activity of NOS. This may explain the mechanism of delayed colonic transit observed in advanced age. (C) 2000 EIs evier Science BN. All rights reserved.