title: Effect of the calcium antagonist amlodipine on the two phases of hypoxic pulmonary vasoconstriction in rat large and small isolated pulmonary arteries.
abstract: Calcium antagonists inhibit hypoxic pulmonary vasoconstriction (HPV), which was recently shown to be biphasic in isolated vessels, but the sensitivity of the two phases to calcium antagonism is unknown. We studied HPV in rat isolated large pulmonary arteries (PA) and resistance pulmonary arteries (PRV), using a small vessel myograph. Two phases of acute hypoxic pulmonary vasoconstriction were confirmed to occur in both sizes of vessel. The first phase was short-lived and was followed by a more persistent phase of gradual onset. The magnitude of the first phase of contraction was greater than the second (p < 0.01). The first phase was reproducible, but the second was variable. Tension generated per square millimeter of vessel during both phases of hypoxic contraction was significantly greater in PRV than in PA (p < 0.05). Amlodipine caused dose-dependent inhibition of the first phase of HPV (p = 0.01), with a greater effect in PRV (p < 0.01). The second phase was not significantly inhibited. These results confirm that HPV is biphasic in isolated large and small PA, with a greater sensitivity of the first phase to calcium antagonism. Therefore, the first phase may represent HPV as observed in vivo.
authors.affiliation: University Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, England.
authors.forename: P A
authors.initials: PA
authors.lastname: Woodmansey
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: K S
authors.initials: KS
authors.lastname: Channer
authors.forename: A H
authors.initials: AH
authors.lastname: Morice
mesh_terms: D017311:Amlodipine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001158:Arteries / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D017311:Amlodipine