In Vivo Evaluation of Left Ventricular Function in Aged SHR by Volume Loading and the Positive Inotropic Effect of Denopamine

Abstract

The positive inotropic effect of denopamine on the hypertrophied heart was studied in 12-months spontaneously hypertensive rats (12-month-SHR) with and without volume loading. Firstly, the influence of volume loading an cardiac function was studied in 12-month-SHR compared with the age-matched normo-tensive Wistar-Kyoto rats (WKY) and younger WKY (4-month-WKY) as well. Left ventricular end-diastolic pressure (LVEDP) and maximum rate of rise of left ventricular pressure (LV dp/dtmax) were significantly higher in SHR than in WKY and 4-month-WKY. Volume loading (saline, 2 ml/kg/min, i.v., for 10 min) caused a marked increase in LVEDP both in SHR and WKY, but a higher elevation of LVEDP was observed in SHR. LV dp/dtmax, however, was increased in WKY and more markedly in 4-month-WKY, while it was not increased in SHR. Administration of denopamine to SHR at a rate of 1 μg/kg/min, i.v., for 10 min before and during 10 min of volume loading produced a marked increase in LV dp/dtmax and a significant decrease in LVEDP. Under denopamine infusion, volume loading caused an increase in LV dp/dtmax and produced a LVEDP elevation to a similar level to that of WKY. Denopamine at this dose caused no significant effects on heart rate and mean arterial blood pressure, indicating a selective inotropic action. The present study suggests that functional cardiac reserve is reduced in the aged SHR and that denopamine increases the functional reserve of the hypertrophied heart.