Angiotensin II receptor subtype antagonists can both stimulate and inhibit salt appetite in rats.
In urethane-anaesthetised male Wistar rats iontophoretic application of the angiotensin II (Ang II) type 1 (AT-1) receptor specific nonpeptide antagonist losartan in the septo-preoptic continuum can produce neuronal excitation of short- and long-term duration which has been interpreted as removal of tonic Ang II-induced inhibition. Mineralocorticoid pretreatment, which increases neuronal sensitivity to Ang II to enhance salt appetite, also removes this losartan-induced long-term excitation. These results suggested steroid modulation of the AT-1 receptor and a complex involvement of Ang II in salt appetite. To investigate the role of the inhibitory action of central Ang II on salt appetite, we gave intracerebroventicular injections of a single, low dose (10 ng) of losartan in normal euhydrated rats and this produced, paradoxically, a progressive increase in salt intake (1.6 +/- 0.3 ml/day to 3.5 +/- 0.9 ml/day, n = 15, P < 0.05). Treatment of these salt enhanced rats with DOCA (0.5 mg/day, s.c., for 3 days) further increased the salt appetite, but then a second i.c.v. injection of the same dose of losartan significantly inhibited the enhanced salt appetite (4.7 +/- 0.7 to 1.3 +/- 0.4, n = 9, P < 0.05). These results provide evidence for a complex action of Ang II on the At-1 receptor mediating the generation of salt appetite that appears to involve either at least two functional subtypes of this AT-1 receptor, as already suggested by previous electrophysiological experiments, or one AT-1 receptor with several activation states.
Centre National de la Recherche Scientifique, Collège de France, Paris, France.
F
F
Liénard
S N
SN
Thornton
F P
FP
Martial
M C
MC
Mousseau
S
S
Nicolaïdis
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004327:Drinking Behavior / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology*; D007276:Injections, Intraventricular; D019808:Losartan; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012462:Saline Solution, Hypertonic; D012965:Sodium Chloride / Q000008:administration & dosage*; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D012462:Saline Solution, Hypertonic; D013777:Tetrazoles; D000804:Angiotensin II; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D019808:Losartan