Area Postrema Ablation Attenuates Activation of Neurones in the Paraventricular Nucleus in Response to Systemic Adrenomedullin

Adrenomedullin (ADM) is a potent vasodilator in the periphery which also acts centrally to increase blood pressure and inhibit drinking, feeding and salt appetite. This study was designed to study the effects of circulating ADM on neuronal activation in autonomic centres in the rat brain and to examine whether neuronal nitric oxide (NO) may participate in these processes. We identified activated neurones 1 h after intravenous (i.v.) injections of ADM (2 nmol/kg) using immunohistochemistry for Fos. The nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemical reaction was used to localize putative NO-producing neurones and double labelling for Fos and NADPH-d was used to identify activated NO producing neurones. To separate baroreceptor-induced neuronal activation in autonomic centres by ADM from other effects which it may have, i.v. infusions of sodium nitroprusside (NP) were used to mimic the hypotensive effects of ADM in control rats. Significantly greater numbers of activated neurones were found in the paraventricular nucleus of the hypothalamus (PVN) and especially in the dorsolateral medial parvocellular division, the nucleus of the solitary tract, and the area postrema (AP) of ADM-treated rats compared to control rats. In addition, the number of activated NO-producing neurones in the PVN was significantly higher in ADM-treated rats compared to rats treated with NP. To determine whether AP is one of the possible routes through which systemic ADM enters the brain to exert its central effects, the APs of rats were ablated by aspiration. One hour after i.v. injections of ADM, significantly fewer PVN neurones were activated in AP ablation rats compared to AP sham ablation rats. Similarly, the number of activated NO-producing neurones in the PVN was significantly lower in AP ablation rats compared to AP sham ablation rats. In conclusion, our results suggest that systemic ADM gains access to the brain through the AP to regulate neuronal activity in autonomic centres and that neuronal NO might be involved in central autonomic and/or neuroendocrine regulation by ADM.