Angiotensin mediates stimulation of ventilation after vasopressin V1 receptor blockade.
We tested the hypothesis that respiration would be stimulated after vasopressin (AVP) V1 receptor blockade because of disinhibition and activation of the renin-angiotensin system. Intravenous infusion of angiotensin II (ANG II) stimulates respiration, presumably centrally, via circumventricular organs. In the present study, the AVP V1 receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid),2-(O-methyl)tyrosine]-Arg8-AVP (PMP; 10 micrograms/kg i.v.) was administered to six awake resting dogs. Measurements were made 30 min prior, and 60 min subsequent, to injection of PMP (protocol 1). In three other protocols, the ANG II blocker saralasin (0.5 microgram.kg-1.min-1 i.v.) was infused starting 20 min before PMP (protocol 2) and 30 min after PMP (protocol 4) and saline was infused (0.2 ml/min) over 90 min as a control (protocol 3). After PMP in protocol 1, alveolar ventilation increased and arterial PCO2 decreased (approximately 3 Torr). ANG II receptor blockade prevented (protocol 2) and reversed (protocol 4) respiratory stimulation by PMP. Despite ventilatory stimulation, plasma renin activity and ANG II were not increased after PMP relative to control (protocol 3). We conclude that AVP acts at V1 receptors to inhibit formation of brain ANG II. Brain ANG II must modulate respiratory control via a circumventricular organ, because systemically administered saralasin, which does not cross the blood-brain barrier, blocked stimulation of respiration.
Walker
J K
JK
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Jennings
D B
DB
D000595:Amino Acid Sequence; D000693:Anaerobiosis; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000097:blood / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012083:Renin / Q000097:blood; D012119:Respiration / Q000187:drug effects*; D015656:Respiratory Mechanics / Q000187:drug effects; D012504:Saralasin / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D065092:Antidiuretic Hormone Receptor Antagonists; C089517:vasopressin, 1-(2-mercapto-2,2-(cyclopentamethylene)propionic acid)-2-(O-methyl)Tyr-8-Arg-; D000804:Angiotensin II; D001127:Arginine Vasopressin; D002245:Carbon Dioxide; D012083:Renin; D012504:Saralasin