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 on cardiac function was studied in 12-month-SHR compared with the age-matched normotensive 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.
