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Altered calcium regulation in the cardiac plasma membrane in experimental renal hypertension
N S Andrawis1, T H Kuo, F Giacomelli
1Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201.
Insights
Hypertension in rats impairs cardiac calcium regulation, decreasing calcium channel binding and ATPase activity. This suggests elevated intracellular calcium contributes to hypertensive cardiomyopathy.
Area of Science:
- Cardiovascular Physiology
- Renal Hypertension Research
- Molecular Cardiology
Background:
- Renal hypertension significantly impacts cardiac function.
- Calcium homeostasis is crucial for myocardial contractility and relaxation.
Purpose of the Study:
- To investigate the factors regulating calcium homeostasis in the cardiac plasma membrane during renal hypertension in a rat model.
- To determine the specific alterations in calcium transport mechanisms and their temporal relationship with hypertension development.
Main Methods:
- Utilized the two kidney-one clip (Goldblatt) rat model of renal hypertension.
- Compared cardiac sarcolemmal preparations from control and hypertensive rats.
- Assessed calcium channel receptor binding (Bmax) and calcium pumping ATPase activity.
- Measured the rate of Na+-Ca2+ exchange.
Main Results:
- Long-term hypertension (4-12 weeks) showed decreased calcium channel receptor binding sites and depressed calcium pumping ATPase activity.
- Short-term hypertension (1-4 weeks) revealed an early decrease in calcium pumping ATPase activity (Vmax) preceding reduced calcium channel binding.
- The decline in Ca2+-ATPase activity was more pronounced than the reduction in Ca2+ channel binding.
Conclusions:
- Altered Ca2+-ATPase activity leads to increased intracellular calcium concentration.
- Elevated intracellular calcium is temporally associated with myocardial lesions in hypertensive rats.
- These findings suggest a significant role for altered Ca2+-ATPase activity and subsequent intracellular calcium increase in the pathogenesis of hypertensive cardiomyopathy.
Abstract:
The factors regulating calcium homeostasis in the cardiac plasma membrane of renal hypertension in the rat (two kidney-one clip, Goldblatt model) have been studied. Comparison of the cardiac sarcolemma from control (C) and hypertensive (H) rats indicates similar protein yield and purity. Study of longer term hypertension (4 to 12 weeks) shows a decrease in the number of calcium channel receptor binding sites (Bmax C: 549 +/- 122 fmol/mg; H: 334 +/- 74 fmol/mg) as well as a depressed calcium pumping ATPase activity (C: 7.6 +/- 2.5 nmol/mg/min; H: 3.8 +/- 1.5 nmol/mg/min). Furthermore, there is a decreased rate of Na+-Ca2+ exchange (C: 5.4 +/- 1.9 nmol/mg/5 s; H: 2.3 +/- 0.9 nmol/mg/5 s). Study of short-term hypertension (1 to 4 weeks) indicates that the earliest change occurs at 1 week with decreased calcium pumping ATPase due to a change of the Vmax of Ca2+ transport (C: 9.7 +/- 1.6 nmol/mg/min; H: 5.4 +/- 1.4 nmol/mg/min). This is then followed by the decreased calcium channel receptor binding. However, the rate and the extent of depression in Ca2+-ATPase activity are much greater than that of Ca2+ channel receptor binding. Since alteration of Ca2+-ATPase is accompanied by an increase in intracellular Ca2+ concentration and there is a temporal association with the onset of myocardial lesions in the hypertensive rats, it is suggested that elevated intracellular calcium concentration as a result of altered Ca2+-ATPase activity may play a significant role in the development of hypertensive cardiomyopathy.