title: Endothelium-independent and -dependent vasodilation in alkalotic and acidotic piglet lungs.
abstract: Although significant pulmonary hypertension can occur in patients treated with either hypocapnic alkalosis or "permissive" hypercapnic acidosis, the effects of sustained alkalosis or acidosis on subsequent vasodilator responses have not been established. This study measured the effects of 60-100 min of sustained alkalosis or acidosis on endothelium-independent and -dependent vasodilation with inhaled nitric oxide (iNO) and acetylcholine (ACh) in isolated lungs from 1-week-old piglets. After stabilization, lungs were divided into control (pH 7.40, PaCO(2) 40 torr, n = 5), alkalotic (pH 7.60, PaCO(2) 25 torr, n = 6), or acidotic (pH 7.25, PaCO(2) 65 torr, n = 5) groups and ventilated with 21% O(2) for 40 min. Acute hypoxic pulmonary vasoconstriction (HPV) was then induced with 4-6% O(2). After a stable pressor response had occurred (approximately 20 min), pulmonary artery dose-response relationships to increasing concentrations of iNO were measured. The iNO was then stopped and after a stable hypoxic pressure had again been reestablished (approximately 20 min), dose-responses to increasing concentrations of ACh were measured. Hypoxic pulmonary vascular resistance (PVR) was similar in all groups. Pulmonary artery pressure dose-response relationships to iNO and ACh were blunted in the alkalosis group, suggesting that both endothelium-independent and -dependent vasodilation were reduced during sustained hypocapnic alkalosis. In contrast, sustained acidosis did not alter subsequent vasodilator responses. Future studies must elucidate the mechanisms underlying blunted pulmonary vasodilation during sustained alkalosis and examine the consequences of sustained alkalosis therapy on subsequent vasodilator responses in clinical practice.
authors.affiliation: Department of Pediatrics, Critical Care Section, Medical College of Wisconsin and Veterans Administration Medical Center, Milwaukee, Wisconsin.
authors.forename: N
authors.initials: N
authors.lastname: Balasubramanyan
authors.forename: T R
authors.initials: TR
authors.lastname: Halla
authors.forename: N S
authors.initials: NS
authors.lastname: Ghanayem
authors.forename: J B
authors.initials: JB
authors.lastname: Gordon
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000138:Acidosis / Q000503:physiopathology*; D000471:Alkalosis / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D004727:Endothelium / Q000502:physiology; D006935:Hypercapnia; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008168:Lung / Q000502:physiology*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation
chemical_list: D009569:Nitric Oxide; D000109:Acetylcholine