Endothelin receptor antagonists in a beagle model of pulmonary hypertension: Contribution to possible potential therapy?

Objectives.This study investigated the pharmacologic effect of endothelin receptor antagonists on cardiopulmonary hemodynamic variables in a beagle model of pulmonary hypertension.Background.We recently developed a beagle model of pulmonary hypertension that allows accurate determination of cardiopulmonary hemodynamic variables and is associated with elevated plasma endothelin-1 concentrations similar to those in pulmonary hypertension in humans.Methods.Twelve beagles (pulmonary hypertension, n = 6; control group, n = 6) were studied during baseline conditions and during right atrial infusion of FR139317 (an ETA receptor antagonist), RES-701-1 (an ETB receptor antagonist), nitroglycerin and prostaglandin E1. Pulmonary hypertension was induced in experimental beagles 8 weeks after injection with 3 mg/kg body weight of dehydromonocrotaline.Results.FR139317 lowered pulmonary artery and systemic arterial pressures in both pulmonary hypertensive and control beagles, with a significantly greater effect on pulmonary artery pressure in pulmonary hypertensive dogs. RES-701-1 tended to increase pulmonary artery pressure only in pulmonary hypertensive beagles. Nitroglycerin depressed pulmonary artery and systemic arterial tone equally well in control and pulmonary hypertensive animals. Prostaglandin E1produced a greater decrease in systemic arterial pressure in pulmonary hypertensive than in normal beagles despite having the same effect on pulmonary artery pressure in both.Conclusions.ETA receptor antagonists decrease pulmonary artery pressure in a beagle model and may therefore be clinically useful for treatment of pulmonary hypertension

Tide gauge response to tsunamis: Measurements at 40 tide gauge stations in Japan

The responses of tide gauges to tsunamis are examined by in situ measurements at 40 stations in northeastern Japan. Recovery of water level in the tide well is measured after the water is drained or added to create a water level difference between the inside and outside of the wells. The recovery times for a 1 m water level difference, estimated from the observations, vary from station to station and range from 65 to 1300 sec. Tsunami waveforms on tide gauge records from the 1983 Japan Sea earthquake are corrected for the observed response. For those stations with the observed recovery times longer than 300 sec, the corrected waveforms differ significantly from the originals and reproduce the inundation heights near the tide gauge stations, indicating that the tide gauge system significantly distorted the tsunami waveforms. At such stations, the correction for the response is necessary for quantification of tsunamis. The recovery time is also computed hydraulically on the basis of the structure of the tide gauge system. The ratio of the observed time to the computed one ranges between 1 and 10 which is attributed to environmentally-induced change of the tide gauge system