Jkl. Walker et Db. Jennings, ANGIOTENSIN MEDIATES STIMULATION OF VENTILATION AFTER VASOPRESSIN V-1RECEPTOR BLOCKADE, Journal of applied physiology, 76(6), 1994, pp. 2517-2526
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.