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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 limb
resistance 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 intraarterial
infusions of substance P, both of which could be diminished by L-NAME (a
nitric oxide synthesis blocker). In another set of experiments, CP-96, 345, a highly
selective antagonist of neurokinin- l receptor, diminished both the nerve-induced as
well 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/, NPYand
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 diarrhoea who were admitted to the ORT centre
at Ethio-Swedish Paediatric hospital for rehydration with DRS. Plasma samples
taken before the start of DRS therapy and another sample col/ected after fu ll
hydration were compared for various variables. Plasma osmolality, sodium and
potassium were lower than controls before DRS therapy all of which increa sed after
full hydration was achieved. Tota l 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 hydromineral 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
in volvement of this pathway in hydromineral balance and release of some
neuropeptides is suggested |
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