Nitric oxide in central nervous structures associated with water balance and micturition

Detta är en avhandling från Department of Clinical Pharmacology, Lund University Hospital, S-221 85 Lund, Sweden

Sammanfattning: The role of nitric oxide (NO) in the central control of water balance and micturition has not yet been established. In the present thesis, where female rats were used, neuronal NO synthase (nNOS) distribution was studied in structures of the central nervous system known to be associated with the above mentioned control. Moreover, the concert action of a NOS inhibitor and oxytocin (OT), intrathecally (i.t.) administered, on cystometry was studied. In rostral circumventricular organs, nNOS-immunoreactive (IR) neurons were observed. In some of these cell bodies, 8-arginine vasopressin (AVP)-immunoreactivity was also found. In the supraoptic nucleus (SON) seven different populations of neuronal cell bodies containing all combinations of nNOS, AVP and OT were demonstrated. The populations in the SON containing either nNOS, but lacking AVP and OT, or nNOS together with AVP and OT, constituted each 2-3% of all observed cell bodies. In the hypothalamic paraventricular nucleus (PVN), about 30% of all nNOS-IR cell bodies were OT-IR. In contrast, around 3% of all nNOS-IR cell bodies were AVP-IR. Further, in the PVN, about 10% of all nNOS-IR neuronal cell bodies were labelled by the retrograde tracer True Blue (TB) injected in the spinal cord. About 40% of these neurons were magnocellular. TB/nNOS cell bodies were most abundant in the caudal PVN, with a clear ipsilateral dominance. OT were found to mediate bladder contractions both in vitro and in vivo. However, when a NOS inhibitor, inactive per se, was injected i.t. prior to OT, the effect of OT was reduced or completely prevented. Moreover, all rats developed overflow incontinence and hindlimb paralysis. The above data suggest a possible interaction between NO and AVP/OT at hypothalamic/suprapontine and spinal levels in the control of water balance and micturition.

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