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 repeated hyperbaric exposures to 5 bar. Exactly the same rat model and experimental 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 the development of these cardiac changes. Losartan, a recently developed 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 ventricular myocardial mass/100 g-1 body mass, thus indicating that Losartan inhibits hyperbarically induced LVH. Microscopic examination revealed no changes in the left ventricle, indicating that Losartan prevents 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 LVP and dP/dt in non-treated test rats in otherwise identical experiments. This indicates that Losartan "normalizes" the cardiac function of test rats after repeated hyperbaric exposures. The systolic arterial pressure, heart rate (HR) and respiratory frequency (RF) were similar in the two groups at 1 bar. However, treatment with Losartan lowered the blood pressure compared to previously non-treated rats. In conclusion, long-term Ang-II receptor blockade prevented previously shown changes in cardiac function and morphology, as well as myocardial mass, after 40 consecutive exposures to 5 bar.
Stuhr
L E
LE
Department of Physiology, Gades Institute, University of Bergen, Norway.
Maehle
B O
BO
D000222:Adaptation, Physiological / Q000187:drug effects*; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D001274:Atmospheric Pressure; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003664:Decompression; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology*; D006334:Heart Function Tests / Q000187:drug effects*; D006371:Helium / Q000494:pharmacology; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D009206:Myocardium / Q000473:pathology; D009584:Nitrogen / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D010313:Partial Pressure; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D006371:Helium; D019808:Losartan; D009584:Nitrogen; D010100:Oxygen