Effects of angiotensin II and its blockers Sar1-lle8-angiotensin II and DuP 753 on drinking in ducks in relation to properties of subfornical organ neurons

Properties of systemically applied angiotensin II in stimulating water intake of normally hydrated ducks were studied and the results compared with properties of angiotensin II-responsive neurons of the subfornical organ which are considered as targets for circulating angiotensin, II acting as a dipsogen. Following intravenous infusion of hypertonic saline (2000 mosmol·kg^-1 at 0.3 ml·min^-1 for 1 h), intravenous infusion of 0.3 ml·min^-1 isotonic saline with angiotensin II (200 ng·min^-1), starting 1 h later, stimulated drinking in each case at an angiotensin II plasma level of about 1400 pg·ml^-1. Without hypertonic priming, the same angiotensin II infusion did not stimulate drinking in each experiment; however, if effective, repeated infusions of ANGII induced stable dipsogenic responses. Angiotensin II infusions did not alter plasma levels of antidiuretic hormone. Sar¹-Ile⁸-angiotensin II, a non-selective angiotensin II antagonist, acted weakly as a partial agonist when injused at a dose 200-fold higher than angiotensin II and effectively blocked the dipsogenic action of angiotensin II; this corresponds to the inhibition of angiotensin II-induced excitation by Sar¹-Ile⁸-angiotensin II observed in duck subfornical organ neurons. DuP 753 (losartan), an angiotensin II antagonist specifically blocking AT₁ receptors in mammals, had equivocal effects on angiotensin II-induced drinking in ducks at rates 50- and 200-fold higher than angiotensin II, which corresponds to the weak inhibitory action of this compound on angiotensin II-induced neuronal excitation in the duck SFO. Blood pressure was only marginally elevated by the applied angiotensin II dose and Sar¹-Ile⁸-angiotensin II had no effect.Abbreviations ANGII angiotensin II - AVT arginine vasotocin - DuP 753 losartan - EDTA ethylene diamine tetra-acetic acid - HR heart rate - ICV intracerebroventricular - IV intravenous - MAP mean arterial pressure - SARILE Sar¹-Ile⁸-angiotensin II - SFO subfornical organ     

Excitatory action of the bird antidiuretic hormone vasotocin on neurons in the subfornical organ

The responsiveness of spontaneously active neurons in the subfornical organ (SFO) of adult ducks to angiotensin II (ANGII) and the bird specific anti-diuretic hormone, arginine vasotocin (AVT), the analog of the mammalian arginine vasopressin (AVP), were investigated in brain slices with extracellular recording technique. 65% (n = 66) of the neurons increased their activity after superfusion with ANGII, the rest were unresponsive. Application of AVT activated 52% (n = 68) of the investigated neurons and like ANGII never caused an inhibition of the spontaneously active SFO neurons. A close correlation exists between the ANGII and AVT sensitivity of duck SFO neurons, because 29 out of 33 neurons were excited by AVT as well as ANGII. The relatively weak antagonistic effect of the V₁-type receptor antagonist Pmp-Tyr (Me)-Arg⁸-vasopressin on the AVT induced excitation suggests a different pharmacology of the bird AVT receptor as compared to the mammalian AVP receptor. The excitatory response of ANGII and AVT on the very same neurons suggest a similar function of both peptides on SFO mediated effects in vivo, such as an increase in water intake. However, peripheral AVT concentrations, unlike ANGII concentrations in the blood are not high enough to activate SFO neurons from the blood side of the blood brain barrier. Therefore AVT is presumably released from synapses of neurons originating within or projecting to the SFO. The identity of the ANGII and AVT reactive neurons suggests that synaptically released AVT should facilitate SFO mediated drinking.Abbreviations _a CSF artificial cerebrospinal fluid - ANGII angiotensin II - AVT arginine vasotocin - AVP arginine vasopressin - ADH antidiuretic hormone - SFO subfornical organ - AVP _4–9 arginine-vasopressin fragment 4–9 - BBB blood-brain barrier