title: Acetazolamide prevents hypoxic pulmonary vasoconstriction in conscious dogs.
abstract: Acute hypoxia increases pulmonary arterial pressure and vascular resistance. Previous studies in isolated smooth muscle and perfused lungs have shown that carbonic anhydrase (CA) inhibition reduces the speed and magnitude of hypoxic pulmonary vasoconstriction (HPV). We studied whether CA inhibition by acetazolamide (Acz) is able to prevent HPV in the unanesthetized animal. Ten chronically tracheotomized, conscious dogs were investigated in three protocols. In all protocols, the dogs breathed 21% O(2) for the first hour and then 8 or 10% O(2) for the next 4 h spontaneously via a ventilator circuit. The protocols were as follows: protocol 1: controls given no Acz, inspired O(2) fraction (Fi(O(2))) = 0.10; protocol 2: Acz infused intravenously (250-mg bolus, followed by 167 microg.kg(-1).min(-1) continuously), Fi(O(2)) = 0.10; protocol 3: Acz given as above, but with Fi(O(2)) reduced to 0.08 to match the arterial Po(2) (Pa(O(2))) observed during hypoxia in controls. Pa(O(2)) was 37 Torr during hypoxia in controls, mean pulmonary arterial pressure increased from 17 +/- 1 to 23 +/- 1 mmHg, and pulmonary vascular resistance increased from 464 +/- 26 to 679 +/- 40 dyn.s(-1).cm(-5) (P < 0.05). In both Acz groups, mean pulmonary arterial pressure was 15 +/- 1 mmHg, and pulmonary vascular resistance ranged between 420 and 440 dyn.s(-1).cm(-5). These values did not change during hypoxia. In dogs given Acz at 10% O(2), the arterial Pa(O(2)) was 50 Torr owing to hyperventilation, whereas in those breathing 8% O(2) the Pa(O(2)) was 37 Torr, equivalent to controls. In conclusion, Acz prevents HPV in conscious spontaneously breathing dogs. The effect is not due to Acz-induced hyperventilation and higher alveolar Po(2), nor to changes in plasma endothelin-1, angiotensin-II, or potassium, and HPV suppression occurs despite the systemic acidosis with CA inhibition.
authors.affiliation: Experimentelle Anaesthesie, Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany. claudia.hoehne@charite.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Höhne
authors.forename: Martin O
authors.initials: MO
authors.lastname: Krebs
authors.forename: Manuela
authors.initials: M
authors.lastname: Seiferheld
authors.forename: Willehad
authors.initials: W
authors.lastname: Boemke
authors.forename: Gabriele
authors.initials: G
authors.lastname: Kaczmarczyk
authors.forename: Erik R
authors.initials: ER
authors.lastname: Swenson
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology*; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000097:blood; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002302:Cardiac Output; D003243:Consciousness; D004285:Dogs; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006339:Heart Rate; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D011188:Potassium / Q000097:blood; D011652:Pulmonary Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D015656:Respiratory Mechanics; D012964:Sodium / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D019332:Endothelin-1; D000804:Angiotensin II; D002245:Carbon Dioxide; D012964:Sodium; D012083:Renin; D000086:Acetazolamide; D011188:Potassium; D010100:Oxygen