Midwall left ventricular performance in salt-loaded Dahl rats: effect of AT1 angiotensin II inhibition.
Academic Article
Overview
abstract
OBJECTIVE: The relationship between left ventricular midwall shortening and circumferential end-systolic stress was studied in Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats after 6-8 weeks of an 8% Na+ diet with or without losartan, an AT1 angiotensin II receptor antagonist. MATERIALS AND METHODS: Losartan was given in drinking water to 13 Dahl S and 13 Dahl R rats, while 14 control Dahl S and 14 control Dahl R rats were given tap water, for 8 weeks. The endpoint was the last blood pressure and echocardiographic examination after 8 weeks or before death for rats which did not survive the entire period. Tail blood pressure was measured in awake animals and two-dimensional guided M-mode echocardiography was used. RESULTS: The left ventricular midwall shortening-circumferential end-systolic stress relationship in 45 normotensive Wistar rats was used to calculate the ratio of observed 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 in weight-matched normotensive Wistar rats (all P<0.05). Afterload-independent midwall shortening was related to the left ventricular chamber dimension in a learning series of 109 rats (64 Goldblatt and 45 normotensive 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 midwall shortening was still higher in Dahl S rats on losartan than in controls (P<0.02). Left ventricular internal diameter-adjusted afterload-independent midwall shortening was inversely related to the left ventricular 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 higher 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 losartan, increased left ventricular performance is related to improved contractility, associated with a blunted development of left ventricular hypertrophy.
