MIDWALL LEFT-VENTRICULAR PERFORMANCE IN SALT-LOADED DAHL RATS - EFFECT OF AT(1) ANGIOTENSIN-II INHIBITION

Objective: The relationship between left ventricular midwall shortenin g and circumferential end-systolic stress was studied in Dahl salt-sen sitive (Dahl S) and salt-resistant (Dahl R) rats after 6-8 weeks of an 8% Na+ diet with or without losartan, an AT(1) angiotensin II recepto r antagonist. Materials and methods: Losartan was given in drinking wa ter to 13 Dahl S and 13 Dahl R rats, while 14 control Dahl S and 14 co ntrol Dahl R rats were given tap water, for 8 weeks. The endpoint was the last blood pressure and echocardiographic examination after 8 week s or before death for rats which did not survive the entire period. Ta il blood pressure was measured in awake animals and two-dimensional gu ided M-mode echocardiography was used. Results: The left ventricular m idwall shortening-circumferential end-systolic stress relationship in 45 normotensive Wistar rats was used to calculate the ratio of observe d to predicted left ventricular midwall fractional shortening. At the endpoint, afterload-independent midwall shortening was higher in Dahl S rats on losartan or tap water, and in Dahl R rats on losartan than i n weight-matched normotensive Wistar rats (all P<0.05). Afterload-inde pendent midwall shortening was related to the left ventricular chamber dimension in a learning series of 109 rats (64 Goldblatt and 45 normo tensive rats on a normal sodium diet; r=0.73) and was adjusted in Dahl rats to a constant left ventricular internal diameter (6.9 mm) by the learning regression equation. The adjusted afterload-independent midw all shortening was still higher in Dahl S rats on losartan than in con trols (P<0.02). Left ventricular internal diameter-adjusted afterload- independent midwall shortening was inversely related to the left ventr icular mass in both Dahl S and Dahl R groups (r=-0.40 and -0.72, both P<0.04). Conclusions: (1) Midwall left ventricular performance was hig her in Dahl S than Dahl R rats on a high-salt diet; (2) this elevation was partially independent of an increase in left ventricular chamber size, an indirect measure of preload; and (3) in Dahl S rats on losart an, increased left ventricular performance is related to improved cont ractility, associated with a blunted development of left ventricular h ypertrophy.