TY - JOUR
T1 - Hypoxic pulmonary vasoconstriction in conscious sheep. Role of mast cell degranulation
AU - Ahmed, T.
AU - Oliver, W.
AU - Frank, B. L.
AU - Robinson, M. J.
AU - Wanner, A.
PY - 1982/10/25
Y1 - 1982/10/25
N2 - We used pharmacologic and histologic techniques to investigate the role of mast cells in the mediation of hypoxic pulmonary vasoconstriction in conscious sheep. Breathing a hypoxic gas mixture (13% O2, 87% nitrogen) caused hypoxic pulmonary vasoconstriction (HPV) with increases in mean pulmonary artery pressure and pulmonary vascular resistance by 97 and 90%, respectively. Intravenous pretreatment with the mast cell membrane stabilizing agent cromolyn sodium (3 mg/kg/min) completely blocked HPV, whereas the H1-histamine receptor antagonist chlorpheniramine, alone or in combination with the H2-receptor antagonist metiamide and the prostaglandin synthetase inhibitor indomethacin, failed to prevent HVP. Cromolyn sodium failed to modify the pulmonary pressor response to infusions of norepinephrine (alpha-agonist), tyramine (catecholamine-releasing agent), and histamine, indicating the specificity of cromolyn sodium action on the mast cells. Electromicroscopic studies of pulmonary perivascular mast cells showed that a 90-min exposure to the hypoxic gas mixture reduced the total number of granules per mast cell to 75% of control. This was blocked by cromolyn sodium pretreatment. We conclude that in conscious sheep, HPV is initiated by the liberation of a mast cell product (other than histamine) that either directly or indirectly causes pulmonary vasoconstriction.
AB - We used pharmacologic and histologic techniques to investigate the role of mast cells in the mediation of hypoxic pulmonary vasoconstriction in conscious sheep. Breathing a hypoxic gas mixture (13% O2, 87% nitrogen) caused hypoxic pulmonary vasoconstriction (HPV) with increases in mean pulmonary artery pressure and pulmonary vascular resistance by 97 and 90%, respectively. Intravenous pretreatment with the mast cell membrane stabilizing agent cromolyn sodium (3 mg/kg/min) completely blocked HPV, whereas the H1-histamine receptor antagonist chlorpheniramine, alone or in combination with the H2-receptor antagonist metiamide and the prostaglandin synthetase inhibitor indomethacin, failed to prevent HVP. Cromolyn sodium failed to modify the pulmonary pressor response to infusions of norepinephrine (alpha-agonist), tyramine (catecholamine-releasing agent), and histamine, indicating the specificity of cromolyn sodium action on the mast cells. Electromicroscopic studies of pulmonary perivascular mast cells showed that a 90-min exposure to the hypoxic gas mixture reduced the total number of granules per mast cell to 75% of control. This was blocked by cromolyn sodium pretreatment. We conclude that in conscious sheep, HPV is initiated by the liberation of a mast cell product (other than histamine) that either directly or indirectly causes pulmonary vasoconstriction.
UR - http://www.scopus.com/inward/record.url?scp=0019991268&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0019991268&partnerID=8YFLogxK
M3 - Article
C2 - 6808879
AN - SCOPUS:0019991268
VL - 126
SP - 291
EP - 297
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 2
ER -