PGF2 alpha causes bronchoconstriction and pulmonary vasoconstriction via thromboxane receptors in rat lung.
We determined the vascular and airway effects of PGF2 alpha and its mechanism of action on isolated-perfused lungs of rats were isolated and perfused at 50 ml/kg/min with Krebs-Henseleit bicarbonate buffer solution containing 3% bovine serum albumin. The lungs were ventilated with 21% O2 and 5% CO2 at a tidal volume of 2 ml. frequency of 60 per minute and positive end expiratory pressure of 3 cmH2O. Following injection of 50 micrograms PGF2 alpha into the afferent pulmonary catheter, there was a marked rise in pulmonary arterial pressure (Ppa) and in resistance to airflow across the lung (RL) and a fall in dynamic lung compliance (Cdyn). Double vascular occlusion technique revealed that 29% of the rise in Ppa was due to an increase in upstream and 71% to downstream resistance. N omega-nitro-L-arginine, 100 microns, a NO synthase inhibitor potentiated the Ppa response two-fold with significant change in airway mechanics. Rat atrial natriuretic factor (r-ANF), 40 micrograms quickly reversed the changes in Ppa, RL and Cdyn. Infusion of r-ANF prior to PGF2 alpha attenuated the Ppa response by 38%, RL by 44% and Cdyn by 12%. SQ 29548, a thromboxane receptor blocker and Cl, a protein kinase C (PKC) inhibitor, fully blocked both the vascular and airway responses to PGF2 alpha. PGF2 alpha is a constrictor of pulmonary vessels and airways in rat lungs via thromboxane SQ 29548 receptors, thansduced by intracellular PKC.
Kang
K H
KH
Department of Internal Medicine, Korea University, Seoul.
Shim
J J
JJ
Banerjee
M
M
Newman
J H
JH
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects*; D008168:Lung / Q000187:drug effects / Q000502:physiology; D011460:Prostaglandins F / Q000008:administration & dosage / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D011460:Prostaglandins F; D017482:Receptors, Thromboxane; D009320:Atrial Natriuretic Factor