The NO synthase inhibitor L-NNA depresses neurohypophysial vasopressin but not its precursor amidating enzymes in salt-loaded rats.
The arginine vasopressin (AVP) producing hypothalamo-neurohypophysial system also has high activities of NO-synthase. Vasopressin production and secretion is drastically upregulated during salt intake and the NO-producing enzyme may be involved. We have studied the influence of the NO-synthase inhibitor NG-nitro-L-arginine (L-NNA) on neurohypophysial and hypothalamic AVP and its amidating enzymes in salt-loaded and control rats as well as on stimulated AVP release in vitro in such rats. Rats were given 2% NaCl solution as the only fluid for 4 days and then returned to tap water. The specific amount of AVP (microgram (mg protein)-1) and the activities of peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), components of its amidating processing enzyme in the supraoptic (SON) and paraventricular nuclear (PVN) regions, did not change during the salt-loading or the following recovery period. In contrast, the AVP and PHM and PAL in the neurohypophysis fell drastically during the salt loading. After that, PHM and PAL increased even more rapidly than AVP, the latter reaching control levels in about 10 days. Salt loading did not change the protein content of the neurohypophysis. When salt loading was performed after administration of L-NNA, the neurohypophysial AVP at the end of the salt loading and 3 days later was lower than in rats not receiving L-NNA, whereas PHM and PAL were not affected. Fractional AVP release from isolated neurohypophyses of salt loaded rats treated with L-NNA and stimulated with K+ was similar to that found in non-treated rats. It is suggested that L-NNA may affect translation or precursor processing of AVP.
Skujins
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Institute of Medical Physiology, University of Copenhagen, Denmark.
Thorn
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D019760:Amidine-Lyases; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000737:chemistry / Q000201:enzymology; D008190:Lyases / Q000187:drug effects / Q000378:metabolism; D008297:Male; D006899:Mixed Function Oxygenases / Q000187:drug effects* / Q000378:metabolism; D009097:Multienzyme Complexes; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000201:enzymology; D010904:Pituitary Gland, Posterior / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000737:chemistry / Q000201:enzymology; D014667:Vasopressins / Q000187:drug effects* / Q000378:metabolism
D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D014667:Vasopressins; D019335:Nitroarginine; D012965:Sodium Chloride; D001120:Arginine; D006899:Mixed Function Oxygenases; D019001:Nitric Oxide Synthase; C035189:peptidylglycine monooxygenase; D008190:Lyases; D019760:Amidine-Lyases; C068521:peptidylamidoglycolate lyase