Vascular hyperresponsiveness in perfused lungs from monocrotaline-treated rats.
Studies were conducted in isolated, buffer-perfused lungs to determine whether altered pulmonary vascular responsiveness could contribute to the evolution of monocrotaline (MCT)-induced pulmonary hypertension. Adult male rats were given a single subcutaneous injection of either 105 mg/kg MCT or its vehicle and vascular responsiveness to angiotensin II, ventilatory hypoxia (3% O2), and KCl was assessed in isolated, buffer-perfused lungs at 4, 7, and 14 days post-treatment. Relative to preparations derived from control animals, vasopressor responses induced by 0.1 microgram, but not 0.05 microgram angiotensin, were augmented at 4 and 7 days but not at 14 days post MCT. Pulmonary vasoconstriction evoked by hypoxic ventilation was enhanced at 4 days but not at 7 or 14 days posttreatment. Pressor responses induced by 30 and 45 mg KCl were not different in treated animals relative to controls at any time post-MCT administration. MCT provoked perivascular edema, but this factor did not seem to contribute to vascular hyperresponsiveness, since the time course of edema did not parallel the time course of augmented responsiveness. Results of the present study indicate that MCT, by an unknown mechanism, causes an early and transient increase in pulmonary vascular responsiveness to some but not all vasoconstrictors. Because the enhanced responsiveness occurred prior to development of pulmonary hypertension, it is unlikely that this alteration contributes to the sustained elevation in pulmonary arterial pressure.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced; D006863:Hydrogen-Ion Concentration; D006976:Hypertension, Pulmonary / Q000139:chemically induced; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D016686:Monocrotaline; D010477:Perfusion; D011651:Pulmonary Artery; D011652:Pulmonary Circulation / Q000187:drug effects*; D011654:Pulmonary Edema / Q000139:chemically induced; D011763:Pyrrolizidine Alkaloids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction
D011763:Pyrrolizidine Alkaloids; D000804:Angiotensin II; D016686:Monocrotaline