THE EFFECT OF LOSARTAN, AN ANGIOTENSIN-II ANTAGONIST, ON CARDIAC-FUNCTION, MASS AND MORPHOLOGY IN RATS AFTER REPEATED HYPERBARIC EXPOSURES

Previously, we have found development of left ventricular hypertrophy (LVH), myocardial necrosis and haemodynamic changes in rats after repe ated hyperbaric exposures to 5 bar. Exactly the same rat model and exp erimental set-up was applied in the present study. The purpose of this study was to investigate if angiotensin II (Ang-II) plays a role in t he development of these cardiac changes. Losartan, a recently develope d non-peptide Ang-II receptor antagonist, was administrated (20 mg kg( -1) day(-1)) to each rat for 40 days. Nine test rats underwent chamber dives daily for 40 consecutive days, and 10 control rats were exposed in the same chamber for an equal period of time, but in air at 1 bar. After 40 days, test rats and control rats had equal right and left ve ntricular myocardial mass/100 g(-1) body mass, thus indicating that Lo sartan inhibits hyperbarically induced LVH. Microscopic examination re vealed no changes in the left ventricle, indicating that Losartan prev ents myocardial necrosis. The left ventricular pressure (LVP) and the maximal velocity of LVP increase and decrease (+/-dP/dt) were similar in the test rats compared to the control rats at 1 bar. Previously we found a higher LW and dP/dt in non-treated test rats in otherwise iden tical experiments. This indicates that Losartan ''normalizes'' the car diac function of test rats after repeated hyperbaric exposures. The sy stolic arterial pressure, heart rate (HR) and respiratory frequency (R F) were similar in the two groups at 1 bar. However, treatment with Lo sartan lowered the blood pressure compared to previously non-treated r ats. In conclusion, long-term Ang-II receptor blockade prevented previ ously shown changes in cardiac function and morphology, as well as myo cardial mass, after 40 consecutive exposures to 5 bar.