L-type calcium current of isolated rat cardiac myocytes in experimental uraemia.

BACKGROUND: End-stage renal failure is associated with a low-output cardiomyopathy, left ventricular hypertrophy and increased QTc dispersion. Cardiac dysfunction is prevalent in patients at the beginning of dialysis and is an important predictor of mortality. Ca(2+) influx through voltage-gated L-type Ca(2+) channels plays a key role in the excitation-contraction coupling of cardiac myocytes. The purpose of this study was to examine the effect of subtotal nephrectomy (SNx) in the rat on both cardiac L-type Ca(2+) currents and action potential duration. METHODS: Wistar rats underwent two-stage SNx; control rats (C) underwent bilateral renal decapsulation. Animals were sacrificed after 8 weeks, and ventricular myocytes were isolated. SNx rats showed a 2-fold increase in plasma urea and creatinine compared with C rats. Whole-cell patch clamp techniques were used to examine L-type Ca(2+) channel currents in isolated cardiac myocytes at 37 degrees C. In separate experiments, the epicardial monophasic action potentials of isolated perfused whole hearts from C and SNx rats were recorded. RESULTS: The amplitude and current-voltage relationships of the L-type Ca(2+) current were not significantly different in myocytes from C (n=11) and SNx (n=8) rats. However, the rate of inactivation of the Ca(2+) current was increased by approximately 15-25% (P<0. 05) in myocytes from SNx rats. The action potential duration (APD(33)) at the apex of the left ventricle was approximately 20% shorter (P<0.01) in hearts from SNx rats as compared with controls. CONCLUSIONS: Renal failure is associated with rapid inactivation of cardiac ventricular myocyte L-type Ca(2+) currents, which may reduce Ca(2+) influx and contribute to shortening of the action potential duration.

Primary hyperaldosteronism: a missed diagnosis in 'essential hypertensives'?

BACKGROUND: It has been recognised recently that primary hyperaldosteronism may be more common than previously thought, the frequency of diagnosis being improved by screening using a plasma aldosterone concentration to renin activity ratio. AIMS: To determine the frequency of primary hyperaldosteronism, screening with both plasma aldosterone to renin concentration (PRC) and activity (PRA) ratios, in normokalaemic subjects previously diagnosed as having essential hypertension. METHODS: Plasma potassium, aldosterone and PRCs and PRA and blood pressure (BP) were measured in 74 hypertensive subjects previously diagnosed by one physician as having essential hypertension. A normal range for plasma aldosterone/renin ratios was determined in 147 control subjects. Hypertensive subjects with elevated aldosterone/renin ratios were further assessed for primary hyperaldosteronism using saline loading and fludrocortisone suppression. Those in whom plasma aldosterone concentration exceeded 140 pmol/L after suppression tests underwent adrenal vein sampling for measurement of aldosterone and cortisol concentrations as well as adrenal CT scanning to diagnose the cause of primary hyperaldosteronism. The main outcome measures were a diagnosis of aldosterone producing adenoma or bilateral adrenal hyperplasia based upon adrenal vein sampling. RESULTS: Four subjects (5%) had an elevated plasma aldosterone to renin ratio using PRC and six (8%) using PRA. Two subjects (2.7%) in this selected population had primary hyperaldosteronism, both of whom had BP > 160/110 mmHg at the time of testing. CONCLUSIONS: The frequency of normokalaemic primary hyperaldosteronism appears to be greater than previously thought, though the true incidence in the general population of hypertensive subjects remains unknown. The sensitivity of diagnosis (but not specificity) may be improved by measurement of the plasma aldosterone/renin ratio and PRC is at least as adequate as PRA for this process.