Tension cost correlates with mechanical and biochemical parameters in different myocardial contractility conditions

OBJECTIVES: Tension cost, the ratio of myosin ATPase activity to tension, reflects the economy of tension development in the myocardium. To evaluate the mechanical advantage represented by the tension cost, we studied papillary muscle contractility and the activity of myosin ATPase in the left ventricles in normal and pathophysiological conditions. METHODS: Experimental protocols were performed using rat left ventricles from: (1) streptozotocin-induced diabetic and control Wistar rats; (2) N-nitro-L-arginine methyl ester (L-NAME) hypertensive and untreated Wistar rats; (3) deoxycorticosterone acetate (DOCA) salt-treated, nephrectomized and salt- and DOCA-treated rats; (4) spontaneous hypertensive rats (SHR) and Wistar Kyoto (WKY) rats; (5) rats with myocardial infarction and shamoperated rats. The isometric force, tetanic tension, and the activity of myosin ATPase were measured. RESULTS: The results obtained from infarcted, diabetic, and deoxycorticosterone acetate-salt-treated rats showed reductions in twitch and tetanic tension compared to the control and sham-operated groups. Twitch and tetanic tension increased in the N-nitro-L-arginine methyl ester-treated rats compared with the Wistar rats. Myosin ATPase activity was depressed in the infarcted, diabetic, and deoxycorticosterone acetate salt-treated rats compared with control and sham-operated rats and was increased in N-nitro-L-arginine methyl ester-treated rats. These parameters did not differ between SHR and WKY rats. In the studied conditions (e.g., post-myocardial infarction, deoxycorticosterone acetate salt-induced hypertension, chronic N-nitro-L-arginine methyl ester treatment, and streptozotocin-induced diabetes), a positive correlation between force or plateau tetanic tension and myosin ATPase activity was observed. CONCLUSION: Our results suggest that the myocardium adapts to force generation by increasing or reducing the tension cost to maintain myocardial contractility with a better mechanical advantage.

Chronic ouabain treatment enhances cardiac myosin ATPase activity in rats.

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.

Ouabain-induced hypertension enhances left ventricular contractility in rats.

Chronic ouabain treatment produces hypertension acting on the central nervous system and at vascular levels. However, cardiac effects in this model of hypertension are still poorly understood. Hence, the effects of hypertension induced by chronic ouabain administration ( approximately 8 microg day(-1), s.c.) for 5 weeks on the cardiac function were studied in Wistar rats. Ouabain induces hypertension but not myocardial hypertrophy. Awake ouabain-treated rats present an increment of the left ventricular systolic pressure and of the maximum positive and negative dP/dt. Isolated papillary muscles from ouabain-treated rats present an increment in isometric force, and this effect was present even when inotropic interventions (external Ca(2+) increment and increased heart rate) were performed. However, the sarcoplasmic reticulum activity and the SERCA-2 protein expression did not change. On the other hand, the activity of myosin ATPase increased without changes in myosin heavy chain protein expression. In addition, the expression of alpha(1) and alpha(2) isoforms of Na(+), K(+)-ATPase also increased in the left ventricle from ouabain-hypertensive rats. The present results showed positive inotropic and lusitropic effects in hearts from awake ouabain-treated rats, which are associated with an increment of the isometric force development and of the activity of myosin ATPase and expression of catalytic subunits of the Na(+), K(+)-ATPase.