Neuropeptides in the Control of Hydromineral Balance and Blood Flow.

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1993-11

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Addis Ababa University

Abstract

Electrical stimulation of the sciatic nerve (2 Hz, 1 ms, 3 v, 40 pulses at 5 min intervals) increased hind limb vascular resistance in rabbits. However, when guanethidine was applied the nerve stimulation induced a decrease in hind limbresistance and an increase in hind limb blood flow which was pulse duration-,frequency- and voltage dependent. The nerve induced responses were not affected by cholinergic or adrenergic blockade. The nerve induced vasodilatory responses were mimicked by local intraarterialinfusions of substance P, both of which could be diminished by L-NAME (anitric oxide synthesis blocker). In another set of experiments, CP-96, 345, a highlyselective antagonist of neurokinin- l receptor, diminished both the nerve-induced aswell as the substance P-induced decreases in hind limb vascular resistance. Neither L-NAME nor CP-96,345 affected the vasodilatory responses elicited by adenosine. In another set of experiments in sheep, L-NMMA (another nitric oxide synthesis blocker) was infused into the lateral ventricles. NO blocking centrally was associated with an increase in free water clearance and a decrease in plasma AVP levels during the infusion. Blood pressure decreased and heart rate increased during the infusion. O-NMMA had little effect. In a similarly prepared sheep, as the previous experiment, water deprivation for 96 hours resulted in a significant increase in plasma A VP and ANG-II levels as well as a significant increase in the levels of cerebrospinal fluid ANG-I/, NPY and CGRP levels all of which paralleled to an increase in plasma osmolality. The levels of the neuropeptides decreased when water was allowed and animals hydrated. The last study was conducted in thirteen children with moderate to severe degree of dehydration secondary to diarrhea who were admitted to the ORT centre at Ethio-Swedish Pediatric hospital for rehydration with DRS. Plasma samples taken before the start of DRS therapy and another sample collected after full hydration were compared for various variables. Plasma osmolality, sodium and potassium were lower than controls before DRS therapy all of which increased after full hydration was achieved. Total plasma protein, measured to assess the state of hydration, decreased after the DRS therapy. The results suggest the importance of the above mentioned neuropeptides in hydro mineral balance and blood flow control in mammals. The involvement of the L-arginine/ NO pathway in blood flow is also demonstrated and the possible central involvement of this pathway in hydro mineral balance and release of some neuropeptides is suggested.

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Hydromineral

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