ANGIOTENSIN MEDIATES STIMULATION OF VENTILATION AFTER VASOPRESSIN V-1RECEPTOR BLOCKADE

We tested the hypothesis that respiration would be stimulated after va sopressin (AVP) V-1 receptor blockade because of disinhibition and act ivation of the renin-angiotensin system. Intravenous infusion of angio tensin II (ANG II) stimulates respiration, presumably centrally, via c ircumventricular organs. In the present study, the AVP V-1 receptor an tagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic aci d),2-(O-methyl)tyrosine]-Arg(8)-AVP (PMP; 10 mu g/kg iv) was administe red to six awake resting dogs. Measurements were made 30 min prior, an d 60 min subsequent, to injection of PMP (protocol 1). In three other protocols, the ANG II blocker saralasin (0.5 mu g.kg(-1).min(-1) iv) w as infused starting 20 min before PMP (protocol 2) and 30 min after PM P (protocol 4) and saline was infused (0.2 ml/min) over 90 min as a co ntrol (protocol 3). After PMP in protocol 1, alveolar ventilation incr eased and arterial PCO2 decreased (similar to 3 Torr). ANG II receptor blockade prevented (protocol 2) and reversed (protocol 4) respiratory stimulation by PMP. Despite ventilatory stimulation, plasma renin act ivity and ANG II were not increased after PMP relative to control (pro tocol 3). We conclude that AVP acts at V-1 receptors to inhibit format ion of brain ANG II. Brain ANG II must modulate respiratory control vi a a circumventricular organ, because systemically administered saralas in, which does not cross the blood-brain barrier, blocked stimulation of respiration.