LOSARTAN REDUCES CARDIAC MASS AND IMPROVES CORONARY FLOW RESERVE IN THE SPONTANEOUSLY HYPERTENSIVE RAT

Objectives To evaluate the effects of losartan administration on cardi ovascular mass, systemic and coronary hemodynamics (rest, maximal trea dmill exercise, and dipyridamole infusion) and on resting regional hem odynamics in conscious spontaneously hypertensive rats (SHR) and Wista r-Kyoto (WKY) rats. Results Although losartan administration (two dose s: 10 and 30 mg/kg per day for 3 weeks by gavage) reduced left ventric ular mass at the higher dose in WKY rats and with both doses in SHR, o nly the higher dose reduced arterial pressure in SHR. Losartan adminis tration did not affect cardiac index, myocardial or other organ flows (radiomicrosphere) at rest in both strains. Significant increases in c ardiac index and coronary flow and decreases in coronary vascular resi stance were observed during exercise in both strains and these respons es were not affected by losartan administration. Compared with those i n WKY rats, coronary flow and flow reserve (dipyridamole) were decreas ed and minimal coronary vascular resistance was increased in untreated SHR. Administration of a higher losartan dose increased coronary flow reserve and decreased minimal coronary vascular resistance (measured during dipyridamole infusion) in SHR. Conclusions These data demonstra ted that losartan administration reduced left ventricular mass, a resp onse that did not seem to be solely dependent on afterload. Furthermor e, cardiac and stroke indices and coronary flow reserve were not chang ed in SHR during maximal treadmill exercise after hypertrophy reversal , even with the lower dose of losartan and when the ventricular afterl oad was similar to that of untreated SHR.