Effects of treppe and calcium on intracellular calcium and function in the failing heart from the spontaneously hypertensive rat.

Abstract

We studied functional and intracellular calcium responses to treppe and extracellular calcium in spontaneously hypertensive rat (SHR) hearts during the transition from compensated pressure overload to failure. Intracellular calcium was measured using aequorin, a bioluminescent Ca 2+ indicator. Experiments were performed with intact, isovolumically contracting, buffer-perfused hearts from three rat groups: (1) aging SHR with evidence of heart failure (SHR-F), (2) age-matched SHR with no evidence of heart failure (SHR-NF), and (3) age-matched normotensive Wistar-Kyoto (WKY) rats. In each experiment, left ventricular pressure and intracellular calcium transients were simultaneously recorded. Hearts were studied at 30°C and paced at a rate of 1.6 Hz while being perfused with oxygenated Krebs-Henseleit solution (95% O 2 /5% CO 2 ) at 100 mm Hg. At the baseline state, peak systolic pressure was greatest in the SHR-NF group and lowest in the SHR-F group. Peak and resting [Ca 2+ ]i were not significantly different among groups; however, the calcium transient was prolonged in the SHR-NF and SHR-F groups. With increasing perfusate [Ca 2+ ] o from 0.5 to 3.0 mmol/L, the relative increases in peak [Ca 2+ ]| and peak systolic pressure were similar among groups. When stimulation rate was increased from 1.6 to 2.0, 2.4, 2.8, and 3.2 Hz, peak [Ca 2+ ]i, peak R elatively few models of cardiac pressure overload have stable hypertrophy persisting over most of the animal's life followed by a state in which chamber and muscle function are impaired. The spontaneously hypertensive rat (SHR) is a model that in many respects parallels the course of human hypertensive heart disease. Studies of both failing human 13 ], and pressure decrease in parallel in the SHR-F heart with increasing stimulation rate, suggesting that impaired calcium cycling may contribute to compromised pump function in the SHR-F heart. (Hypertension. 1994^4J47-356.) Keywords • calcium • heart hypertrophy muscle, cardiac heart failure, congestive in the force-frequency response between failing and nonfailing human myocardia and a reduced ability of the failing heart to increase force at increasing stimulation rates.6 Studies of isolated ventricular strips from failing human ventricles demonstrate that increased stimulation rates enhance disturbances in calcium handling 1 ' 2 and force development.6 It is well recognized that treppe and increasing [Ca 2+ ] o lead to an increase in [Ca 2+ ], and the number of occupied crossbridges per unit time, which in turn results in an increase in myocardial energy demands. In addition, both of these interventions lead to increases in [Ca 2+ ], and a greater load on intracellular calcium control systems. However, one problem with isolated muscle studies is the uncertainty regarding diffusion, inherent in isolated muscle studies, and the applicability to in vivo physiology. To bridge the gap between isolated muscle studies and in vivo physiology, we have carried out studies in the isolated perfused heart prepa...

Phosphorylation of RyR2and shortening of RyR2cluster spacing in spontaneously hypertensive rat with heart failure

“…During HF, HW/BW was higher in SHR than in age-matched WKY [6.19 Ϯ 1.68 (n ϭ 5) vs. 3.63 Ϯ 1.13 mg/g (n ϭ 18)], but the individual variation was greater during HF, most likely due to cardiac cachexia (P Ͻ 0.1, t-test). Consistent with previous studies showing echocardiographic evidence for HF in Ͼ1.5-yr-old SHR (6,8,34,35), we found clinical signs of HF (e.g., severe hypertrophy or chamber dilation, ascites, pericardial effusion, chest edema, and lung edema) in SHR at postmortem examination.…”

Cardiomyocyte Functions Couple with Left Ventricular Geometric Patterns in Hypertension.

“…Some studies have demonstrated abnormal Ca2+ handling induced by an altered SR function in pressure-overloaded hypertrophy (31). However, in our previous study (12), Ca2+-ATPase messenger RNA levels in DS rats with compensated hypertrophy were not significantly different than those in DR rats.…”

“…However, the mechanism for the disturbed Na+/Ca2+ exchange is unknown. In addition, some investigators have reported a change in myofilament Ca2+ sensitivity and a shift in myosin heavy chain isoforms in pressure-overloaded hypertrophy (31,32). These findings may be related to the myocyte dysfunction at high frequencies.…”

Intracellular calcium and the relationship to contractility in an avian model of heart failure

“…With the utilization of intracellular calcium indicators, intracellular calcium transients can be recorded in multicellular preparations and in isolated myocytes. The spontaneously hypertensive rat model and Syrian hamster model have been extensively investigated with regard to [Ca 2+ ] i handling (Bing et al 1988;Brooks et al 1994Brooks et al ,1997Brooksby et al 1992Brooksby et al , 1993Finkel et al 1987;Pfeffer and Frohlich 1973;Sen and Smith 1994;Sen et al 1990). Rodent models, like all animal models, however, have limitations Gwathmey andDavidoff 1993,1994).…”