ACUTE EFFECTS OF ATRIAL-NATRIURETIC-PEPTIDE ON LUNG-MECHANICS AND HEMODYNAMICS IN AWAKE SHEEP

The purpose of this study was to measure airway and hemodynamic effects of atrial natriuretic peptide (ANP) and its efficacy in counteracting the changes in lung mechanics that occur with aerosol histamine and carbachol. Synthetic human α-ANP was injected into the pulmonary arteries of awake sheep chronically instrumented for measurement of lung mechanics and hemodynamics (n = 7). Base-line dynamic lung compliance (Cdyn) and pulmonary resistance (RL) did not change after ANP injection. On separate days, the dose required to reduce Cdyn to 65% of base line (ED65Cdyn) to progressive doses of aerosol histamine and the dose required to increase RL by 100% of the base-line values (ED200RL) to progressive doses of aerosol carbachol were determined. ANP was given as bolus injections of 1, 5, and 10 μg/kg 3 min after either the ED65Cdyn or ED200RL doses of histamine and carbachol, respectively, and the airway response was monitored for 10 min. ANP significantly reversed the rise in RL after carbachol administration (n = 10). This action of ANP was not altered by cyclooxygenase inhibition with ibuprofen. ANP did not reverse the reduction in Cdyn caused by either histamine (n = 7) or carbachol. The bronchodilating effect of ANP appears to be more prominent in the larger central airways than in the peripheral airways. The hemodynamic effects of ANP were similar to those reported by others. Heart rate and cardiac output had a biphasic response, with an initial rise followed by a drop below the base line. Systemic arterial and left atrial pressures decreased significantly. Pulmonary arterial pressure did not change significantly. Urinary output increased five- to eightfold. ANP alone caused a significant increase in hematocrit.