title: Potentiation of pulmonary arteriolar vasoconstriction to endothelin-1 by inhibition of nitric oxide synthesis in the intact lung.
abstract: OBJECTIVE
  To observe pulmonary arteriolar effects of endothelin-1 (ET-1) in the intact lung and determine if constriction to ET-1 is potentiated by inhibition of nitric oxide (NO) synthesis.
  
  
  METHODS
  In anesthetized male Sprague-Dawley rats with open chest, the lungs were ventilated with air through the lower trachea and in vivo responses of pulmonary arterioles were examined by video microscopy. Observations were made when the lungs were statically inflated with oxygen to a pressure of approximately 10 cm H2O for brief periods. A lens with a dipping cone was held at the pleural surface. ET-1 (10(-7)-10(-5)M; approximately 0.1 ml) was applied topically to the fluid layer under the dipping cone.
  
  
  RESULTS
  ET-1 (10(-6)M) constricted parent arterioles 60 +/- 5 microns in diameter by 52 +/- 12% (range: 20-100%) and branches 45 +/- 3 microns in diameter by 36 +/- 4% (19-48%). Constriction persisted and there was a dramatic long-lasting decrease in flow. Alveolar walls quickly became pale, indicating reduced capillary perfusion. A lower concentration of ET-1 (10(-7)M) constricted (p > 0.05) parent arterioles 61 +/- 4 microns in diameter by 7 +/- 3% initially, and by 13 +/- 8% after 14 +/- 2 minutes, while smaller branches did not respond. In separate experiments, infusion of the NO synthase inhibitor L-NAME (1 mg/kg per minute), modestly (10 +/- 3%) decreased (p < 0.05) baseline parent arteriolar diameter from 72 +/- 7 microns to 64 +/- 5 microns. Branch diameter changed insignificantly from 42 +/- 7 microns to 38 +/- 7 microns. After L-NAME, ET-1 (10(-7)M) constricted (p < 0.05) parent arterioles by 17 +/- 4% initially and 40 +/- 14% after 14 +/- 2 minutes. Concurrently, branches constricted (p < 0.05) by 14 +/- 4% and 26 +/- 15%.
  
  
  CONCLUSIONS
  Arterioles less than 80 microns in diameter were very responsive to ET-1, which could be a factor in altering pulmonary microvascular resistance. Inhibition of NO synthesis appears to potentiate constriction to ET-1.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, University of Louisville, KY 40292, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Roberts
authors.forename: D W
authors.initials: DW
authors.lastname: Slaaf
authors.forename: I G
authors.initials: IG
authors.lastname: Joshua
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D011650:Pulmonary Alveoli / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester