Losartan reduces cardiac mass and improves coronary flow reserve in the spontaneously hypertensive rat.
OBJECTIVE
To evaluate the effects of losartan administration on cardiovascular mass, systemic and coronary hemodynamics (rest, maximal treadmill exercise, and dipyridamole infusion) and on resting regional hemodynamics in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats.


RESULTS
Although losartan administration (two doses: 10 and 30 mg/kg per day for 3 weeks by gavage) reduced left ventricular mass at the higher dose in WKY rats and with both doses in SHR, only the higher dose reduced arterial pressure in SHR. Losartan administration did not affect cardiac index, myocardial or other organ flows (radiomicrosphere) at rest in both strains. Significant increases in cardiac index and coronary flow and decreases in coronary vascular resistance were observed during exercise in both strains and these responses were not affected by losartan administration. Compared with those in WKY rats, coronary flow and flow reserve (dipyridamole) were decreased 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 demonstrated that losartan administration reduced left ventricular mass, a response that did not seem to be solely dependent on afterload. Furthermore, cardiac and stroke indices and coronary flow reserve were not changed in SHR during maximal treadmill exercise after hypertrophy reversal, even with the lower dose of losartan and when the ventricular afterload was similar to that of untreated SHR.
Kaneko
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K
Hypertension Research Laboratories, Alton Ochsner Medical Foundation, New Orleans, LA 70121, USA.
Susic
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D
Nunez
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Frohlich
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ED
D000804:Angiotensin II / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000517:prevention & control*; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan