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Conscious rats were given i. p. polyethylene glycol (PEG) or dextran injections to compare their efficacy in inducing moderate hypovolaemia. Dextran was found unsuitable, producing large variability in the the plasma vasopressin (A VP) concentrations. Putative neurotransmitters involved in the A VP response to hypovolaemia and in basal release were examined using opioid, and ß-adrenoceptor and dopamine receptor-blocking agents. A dose of PEG was chosen to produce a decrease in blood volume of approx 14.5% giving plasma AVP concentrations of 19.0±4.6 pmol/1. Naloxone and phenoxy- benzamine failed to influence AVP release under both hypovolaemic and basal conditions. Prazosin also failed to influence the AVP response. In contrast propranolol elevated the plasma AVP concentrations in both conditions. Haloperidol enhanced basal AVP release but did not influence release during hypovolaemia. Guanethidine pretreatment partially blocked the response to hypovolaemia, but did not affect basal plasma AVP. Thus it appears that aminergic pathways have an inhibitory influence on AVP release under hypovolaemic and basal conditions. However, endogenous opioids do not appear to contribute significantly to the hypovolaemic response.
We examined the effects of various NO inhibitors on the healing of DSS-induced rat colitis. Experimental colitis was induced by feeding rats for 6 days with 2.5% DSS in drinking water. After DSS treatment, the animals were fed normally and killed various days up to 7 days later. L-NAME (a nonselective NOS inhibitor) or aminoguanidine (a selective iNOS inhibitor) was given p.o. twice daily for 6 days starting from the termination of DSS treatment. The area of lesions, colon length and MPO activity were measured on day 7 after DSS treatment. DSS treatment caused severe lesions in the colon, accompanied by an increase in MPO activity and a decrease in colon length. The lesions healed gradually after discontinuation of DSS treatment, with a histological restoration and subsidence of inflammation. The healing of DSS-induced colonic lesions was significantly impaired by daily administration of L-NAME or aminoguanidine, the effects being all but equivalent between these drugs, and the effect of L-NAME was significantly reverted by the co-administration of L-arginine. The expression of nNOS protein was observed in the colonic mucosa with or without DSS treatment, while those of iNOS and eNOS were markedly upregulated after DSS treatment. Likewise, the expression of VEGF was also up-regulated in the colon following DSS treatment, and this response was suppressed by both L-NAME and aminoguanidine. These results suggest that endogenous NO produced by mainly iNOS and partly eNOS contributes to the healing of DSS-induced colonic lesions, through the upregulation of VEGF expression and enhancement of angiogenesis.
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