CHRONIC OUABAIN TREATMENT ENHANCES CARDIAC MYOSIN ATPase ACTIVITY IN RATS

Abstract

1. Chronic ouabain administration increases blood pressure and produces a positive inotropic effect. However, the temporal changes capable of affecting both arterial and ventricular pressures and myosin ATPase activity during the induced hypertension have not been determined. 2. The aim of the present study was to investigate the time-course of the induction of hypertension to define when changes occur in Wistar rats treated with 25 mg/kg per day, s.c., ouabain for 3, 7, 15 or 30 days. 3. In anaesthetized rats, diastolic blood pressure increased after 7 days treatment with ouabain and after 15 and 30 days treatment, increases were observed in systolic blood pressure, left ventricular systolic pressure and myosin ATPase activity. After 15 days treatment, heart rate (HR) also increased, but after 30 days treatment HR returned to control levels. However, only after 30 days treatment did the left ventricular positive and negative first derivatives of intraventricular pressure (dP/dt(max) and dP/dt(min), respectively) increase. Increased arterial and left ventricular systolic pressures and myosin ATPase activity observed after 15 days treatment maintained similar levels as those after 30 days treatment. 4. The results suggest that changes in arterial and left ventricular pressures, HR and myosin ATPase activity induced by chronic ouabain treatment are time dependent, increasing after 15 days treatment. After 30 days treatment, the increase in systolic and diastolic arterial and ventricular pressures remained stable, as did inotropism. Normalization of HR after 30 days treatment suggests that during the period from Day 16 to Day 30 ouabain-induced hypertension is dependent, at least in part, on increased sympathetic activity.

Low-dose ouabain administration increases Na+,K+-ATPase activity and reduces cardiac force development in rats

“…Thus, the increase in sympathetic activity [5,18] and the greater release of noradrenaline from nerve terminals [27] which are associated with the vascular smooth muscle sensitization [26,28] and activation of ACE activity [21], may contribute to increased blood pressure following ouabain treatment for 15 days. However, as observed in this study and in other report [17], ouabain also increased diastolic blood pressure. Therefore, it could reflect an increase in vascular resistance that would elevate the afterload, increasing systolic blood pressure [29].…”

“…As previously described [17], systolic and diastolic arterial pressures were increased after ouabain treatment when compared with controls (Table 1). Heart rate was also increased in rats treated with ouabain for 15 days.…”

“…We have recently showed an improvement in ventricular performance of ouabain-treated rats after treatment for 7 or 15 days [17], which may be due to increased sympathetic activity Pharmacological Reports 67 (2015) 253-259 [5,18]. Furthermore, increased blood pressure as well as isometric force and myosin ATPase activity was observed after 5 weeks of ouabain treatment [19].…”

“…We have recently showed an improvement in ventricular performance of ouabain-treated rats after treatment for 7 or 15 days [17], which may be due to increased sympathetic activity A B S T R A C T Background: Ouabain is a digitalis compound that inhibits the Na + ,K + -ATPase (NKA) activity inducing increment in cardiac force. However, this effect seems to be dose dependent.…”

“…The above reported increase in intracellular Na + reduces the electrochemical gradient to Ca 2+ extrusion. Such effect reduces NCX activity, and consequently increases the amount of Ca 2+ available for contraction [14][15][16] providing a positive inotropic effect.We have recently showed an improvement in ventricular performance of ouabain-treated rats after treatment for 7 or 15 days [17], which may be due to increased sympathetic activity A B S T R A C T Background: Ouabain is a digitalis compound that inhibits the Na + ,K + -ATPase (NKA) activity inducing increment in cardiac force. However, this effect seems to be dose dependent.…”