Neutral endopeptidase inhibition increases the potency of ANP in isolated rat pulmonary resistance vessels and isolated blood perfused lungs

We have investigated the effects of the neutral endopeptidase inhibitor, SCH 42354, on the vasoreactivity of atrial natriuretic peptide (ANP) in rat isolated pulmonary resistance vessels (PRV) and isolated perfused lungs (IPL). PRV (n = 37) were mounted onto the jaws of a myograph and precontracted with PGF2alpha (100 mu M). Concentration-responses to ANP (0.17 to 340 nM) were determined before and after the addition of SCH 42354 (10, 30 and 100 nM). Each concentration of SCH 42354 caused a significant increase in potency (- log EC50) of ANP in isolated PRV. Lungs from normoxic rats (n = 13) were isolated and perfused with whole blood. An increase in pulmonary artery pressure was achieved by ventilating with an hypoxic gas mixture and concentration-responses obtained by incremental additions of ANP (40 nM to 12 mu M), before and after the addition of SCH 42354 (100 nM). SCH 42354 significantly increased the potency (- log EC50) of ANP in the rat IPL. ANP is partly metabolized by NEP. That an inhibitor of NEP increased the potency of ANP in isolated pulmonary vessels, and in isolated perfused whole lungs, suggested that SCH 42354 may be having a local action within the pulmonary vasculature.     

Los Angeles airport noise and mortality--faulty analysis and public policy

A well-publicized investigation in Los Angeles showed a higher mortality rate in 1970-1971 among residents in a high-noise area near Los Angeles International Airport than in a low-noise control area. The authors of this report attributed the difference to the effects of jet aircraft noise. A reanalysis of the data did not confirm the original results. Once the confounding effects of age, race, and sex were taken into account by direct and indirect methods of standardization, there was little difference in the mortality experience of the airport and control areas. Adjusted mortality rates due to all causes, cardiovascular diseases, or cerebrovascular disease did not differ appreciably between the two areas and were nearly identical to those of Los Angeles County during 1970.