OPIOID PEPTIDES AND THE CNS REGULATION OF HYDRATION

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It is postulated that opioid peptides act in the CNS to regulate blood pressure and hydration. Two sites of action are proposed. At the first site, in the neurohypophysis, opiod peptides are postulated to: 1) promote the preferential release of vaso-pressin (VP) during hemorrhage and dehydration by supressing release of oxytocin and promote the preferential release of oxytocin during parturition and sucklilng by inhibiting release of VP. The hypothesis will be tested in vivo and in vitro using an opiate receptor antogonist, naloxone. The effect of naloxone on [VP] and [oxitocin] in plasma and the neural lobe will be determined by RIA when secretion of neurohypophysial hormones is stimulated in conscious rats by parturition, increased tonicity of plasma and [NaCl] in cerebrospinal fluid (CSF), nicotine, carbachol, histamine and estradiol. The site of opiate action in the neurophypophysis will be studied in vitro using explants of the intact hypothalamo-neurohypohysial system (HNS) cultured with the hypothalamic and posterior pituitary portions, either in the same compartment, or in separate chambers. Oxytocin and VP released by osmotic stimulation of the HNS in cluture will be compared after blocking opiate receptors with naloxone in the whole explant or only on the hypothalamic or pituitary side. The second site proposed where opioid peptides regulate blooc pressure and hydration is in circumventricular structures including the subfornical organ, organum vasculosum of the lamina terminalis, choroid plexus and ependymal cells lining the III cerebroventricle. It is proposed that opiod peptides act at these sites to inhbit drinking and release af VP by affecting Na, K ATPase, the putative Na receptor. The effect of opioid peptides on the activity of Na, K ATPase will be measured by quantitative cytochemistry in thse circumventricular structures after stimuli known to regulate CNS mechanisms controlling blood pressure and hydration. It is proposed that abnormal modulation of these systems by opioid peptides is involved in the development of hypertension. Therefore, responses of spontaneously hypertnesive rats with their normotnesive controls will be compared at various ages to determine if naloxone alters: a) preferential release of VP and oxytocin during dhydration, in vivo and b) osmotic-stimulated release of VP and oxytocin when applied to either the hypothalamic or pituitary side of HNS explants in vitro.