NEUROPEPTIDE-Y GENE-EXPRESSION AND RECEPTOR AUTORADIOGRAPHY IN HYPERTENSIVE AND NORMOTENSIVE RAT-BRAIN

Neurones containing neuropeptide Y (NPY) may participate in central ca rdiovascular control by tonically influencing barosensitive neurones w ithin the nucleus tractus solitarius. The present study has employed b oth in situ hybridisation histochemistry and receptor autoradiography, to visualise the expression of prepro-NPY mRNA in the forebrain and t o determine the NPY receptor subtype(s) in the brainstem, respectively . Prepro-NPY gene expression was visualised in the hypothalamus, corte x, dentate gyrus and lateral reticular thalamus from age-matched spont aneously hypertensive rats (SHR) and normotensive Don Ryu rats (DRY) a nd Wistar Kyoto rats (WKY). Quantitative densitometry revealed an incr ease in the NPY transcript in the arcuate nucleus of SHR rats compared to their normotensive counterparts. Autoradiography using [I-125]Bolt on-Hunter-NPY (BH-NPY, 15 pM) demonstrated NPY binding sites in the ar ea postrema, the commissural nucleus tractus solitarius (cNTS) and the inferior olivary complex. NPY(1 mu M) and peptide YY (1 mu M), but no t [Leu(31),Pro(34)]NPY (10-100 nM), fully inhibited the binding of [I- 125]BH-NPY. These results indicate that NPY receptors of the Y-2 subty pe predominate in the dorsal vagal complex. Unilateral nodose ganglion ectomy resulted in a partial loss of NPY binding sites in the commissu ral NTS, but not the area postrema, suggesting that a proportion of bi nding sites (Y-2 subtype) are present on central vagal terminals. Whil e all three rat strains appear to have the same relative proportions o f NPY receptor subtypes in the brainstem, the relevance of the differe ntial NPY gene expression in the arcuate nucleus regarding central car diovascular control mechanisms and/or the pathogenesis of hypertension remains to be elucidated.