Roles of brain angiotensins II and III in thirst and sodium appetite.
The current study examined the effects of intracerebroventricular (icv) infused aminopeptidase-resistant analogs of angiotensin II (AngII) and angiotensin III (AngIII) on thirst and sodium appetite. The analogs, [D-Asp1D-Arg2]AngII and [D-Arg1]AngIII, were further protected from degradation by pretreatment with the aminopeptidase A inhibitor, EC33, or the aminopeptidase N inhibitor, PC18. Prior to icv infusions, rats were sodium depleted with furosemide, followed by the angiotensin-converting enzyme inhibitor captopril, to block endogenous angiotensin formation. Both angiotensin analogs, at either of the two doses, were capable of eliciting fluid intakes of water and 0.3 M NaCl. Water and saline intakes were increased to a similar extent by 125 and 1250 pmol of [D-Asp1D-Arg2]AngII. [D-Arg1]AngIII produced a dose-dependent increase in water intake, whereas saline intake was equivalently increased by the 125 and 1250 pmol infusions. Pretreatment with EC33 or PC18 decreased water and saline intakes in response to [D-Asp1D-Arg2]AngII, while pretreatment with PC18 altered the time course of the [D-Arg1]AngIII-induced water and saline intakes. The ability of both inhibitors to decrease, but not completely block, AngII analog-induced intakes, coupled with the altered time course of the responses induced by the AngIII analog in the presence of PC18, supports the hypothesis that both AngII and AngIII are active ligands in brain angiotensin-mediated thirst and sodium appetite. However, these results do not resolve the primary question of whether conversion of AngII to AngIII is a prerequisite to dipsogenic and salt appetite responses in the brain.
Wilson
Wendy L
WL
Department of Psychology, Washington State University, Pullman, WA 99164-4820, USA. wwilson@wsu.edu
Roques
Bernard P
BP
Llorens-Cortes
Catherine
C
Speth
Robert C
RC
Harding
Joseph W
JW
Wright
John W
JW
D000804:Angiotensin II / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D000805:Angiotensin III / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005665:Furosemide / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D013451:Sulfonic Acids / Q000494:pharmacology; D013894:Thirst / Q000187:drug effects / Q000502:physiology*
C472311:2-amino-4-methylsulfonyl butane thiol; D000806:Angiotensin-Converting Enzyme Inhibitors; C101968:EC 33; D017673:Sodium Chloride, Dietary; D049994:Sodium Potassium Chloride Symporter Inhibitors; D013451:Sulfonic Acids; D000804:Angiotensin II; D000805:Angiotensin III; D005665:Furosemide; D002216:Captopril; D008715:Methionine