Effects of angiotensinogen antisense oligonucleotides on fluid intake in response to different dipsogenic stimuli in the rat.
The role of centrally synthesised angiotensinogen in neural mechanisms subserving water drinking in rats was investigated by injecting antisense oligonucleotides complementary to rat angiotensinogen mRNA into the brain with the aim of inhibiting cerebral angiotensinogen synthesis. Phosphorothioate antisense oligonucleotides (18 mer) encompassing the translation start codon were injected into the lateral ventricle of rats and their responses to a number of dipsogenic stimuli tested. These were: intracerebroventricular (i.c.v.) renin, i.c.v. angiotensin II, i.c.v. carbachol, subcutaneous isoproterenol, intravenous hypertonic saline, water deprivation for 24 h or subcutaneous injection of polyethylene glycol. Antisense treatment significantly reduced (by approximately 50%) the volume of water drunk in response to i.c.v. injection of renin or subcutaneous isoproterenol, but did not reduce water intake elicited by the other dipsogenic stimuli. The i.c.v. administration of mismatch, scrambled or sense oligonucleotides did not inhibit water intake. These data suggest that centrally produced angiotensinogen may have a role in neural pathways subserving isoproterenol-induced drinking.
Sinnayah
P
P
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Kachab
E
E
Haralambidis
J
J
Coghlan
J P
JP
McKinley
M J
MJ
D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D004327:Drinking Behavior / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D007276:Injections, Intraventricular; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009434:Neural Pathways / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000494:pharmacology; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D014868:Water Deprivation
D016376:Oligonucleotides, Antisense; D012462:Saline Solution, Hypertonic; D000808:Angiotensinogen; D012083:Renin; D007545:Isoproterenol