Mineralocorticoid modulation of central angiotensin-induced neuronal activity, water intake and sodium appetite.
Central angiotensin II (AngII) stimulates water and salt solution intake. Pretreatment with low-dose mineralocorticoid (DOCA) enhances this AngII-induced intake of salt solutions (the synergy theory) in Wistar and Sprague Dawley rats but not in Fischer rats. This response is mediated via the AT-1 receptor. Electrophysiological experiments using iontophoretic application of AngII and the AT-1 receptor-specific non-peptide antagonist losartan showed excitation of neurons in the preoptic/medial septum region of urethane-anesthetized male Wistar rats. DOCA pretreatment further enhances this neuronal excitation in response to AngII and reduces the responses to losartan. This generated the hypothesis that DOCA-enhanced AngII-induced neuronal excitation is the neural support for the synergy theory. AT-2 receptors modulate these intake responses depending on sodium in the diet, and diuretic-induced dehydration during pregnancy produces a higher salt intake in the offspring. AngII-induced salt and water intakes were tested in offspring from Sprague Dawley mothers with only 1.8% NaCl to drink in which half were treated with furosemide. The important observations were a) the AT-1 antagonist alone suppressed intakes in offspring from mothers not treated with furosemide, b) both AT-1 and AT-2 antagonists suppressed intakes in offspring from furosemide-treated mothers, and c) combined administration of AT-1 and AT-2 antagonists greatly suppressed water intake in offspring from mothers not treated with furosemide. These results suggest that AT-1 and AT-2 receptors have variable properties (receptor number and/or second messengers). Furthermore, the activity and function of these central AngII receptors depend on the background mineralocorticoid levels. The exact mechanism of this influence, however, remains to be determined.
Thornton
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U684 UHP-INSERM, Faculté de Médecine, Université Henri Poincaré, Nancy, France. simon.thornton@nancy.inserm.fr
Omouessi
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Falconetti
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D000804:Angiotensin II / Q000008:administration & dosage / Q000502:physiology*; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects*; D004327:Drinking Behavior / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D008297:Male; D008901:Mineralocorticoids / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000378:metabolism*
D008901:Mineralocorticoids; D000804:Angiotensin II; D012965:Sodium Chloride