Potassium supplementation improves the natriuretic response to central volume expansion in primary aldosteronism

Potassium depletion induced by dietary potassium restriction is known to cause sodium retention, while potassium supplementation is known to increase urinary sodium excretion. However, the ability of potassium deficiency to affect mineralocorticoid-induced sodium retention in aldosterone-producing adenoma (APA) subjects has not been extensively investigated, neither in baseline conditions nor when facilitating natriuresis through a physiological manoeuver such as central blood volume expansion. With the aim of testing the hypothesis that potassium supplementation would attenuate the mineralocorticoid-induced sodium retention, in 7 APA patients elevation of serum potassium was obtained by infusion of isosmotic potassium chloride (KCl) at a constant rate of 36 mmol/h for a 2-hour period for 5 consecutive days. The same patients were also submitted to acute central volume expansion by head-out water immersion (WI) associated with either low or normal serum potassium levels. The assessment of natriuresis in baseline condition and during WI was also performed in 10 age-matched control subjects. Central hypervolemia by WI induced a significant natriuretic response in APA hypokalemic subjects; on the other hand, in the same APA subjects giving potassium supplementation, WI-induced urinary sodium excretion was significantly higher (P <.001) than that obtained during WI at normal potassium intake (hypokalemic condition). Blood pressure responses and hormonal profiles were almost superimposable during the 2 WI experiments performed at different serum potassium levels. By confirming that amelioration of hypokalemia attenuates mineralocorticoid-induced sodium retention, this study also suggests that potassium intake may represent an important determinant of mineralocorticoid escape.     

Plasma and skeletal muscle free amino acids in type I, insulin-treated diabetic subjects

Insulin-dependent diabetes mellitus (IDDM) induces plasma amino acid (AA) abnormalities, including low alanine and high branched-chain (BCAA). While insulin treatment restores plasma AA pattern, proline, methionine, valine, isoleucine, and total BCAA remain elevated in skeletal muscle intracellular water. This suggests that the restoration of plasma AA concentrations is not a satisfactory index of recovered AA metabolism in IDDM.     

Renin-aldosterone system suppression during water immersion in renovascular hypertension

We studied renin-aldosterone system behaviour in five renovascular hypertensive patients during central hypervolaemia by water immersion to the neck. Water immersion significantly suppressed the high peripheral renin levels of the patients despite an autonomic renin secretion from the stenotic kidney, a significant reduction of mean blood pressure and an increase in distal tubule sodium concentration. The effect of immersion on plasma aldosterone appeared to be primarily mediated via suppression of plasma renin activity (PRA). Our data suggest that: (a) the renin secretion is mainly modulated by cardiopulmonary receptors activity; (b) the neurogenic reflex control of plasma renin activity is very effective in renovascular hypertension.     

Role of renal hemodynamics in the exaggerated natriuresis of essential hypertension

Extracellular fluid volume expansion is known to produce exaggerated natriuresis in essential hypertension. In order to assess the role of hemodynamic and intrarenal physical factors upon natriuretic response to central volume expansion, two hour water immersion (WI) experiments were made in six uncomplicated essential hypertensives and six normotensive healthy controls. Before and during WI we measured mean arterial pressure (MAP), urine flow (V/min), sodium (UNaV) and potassium (UKV) excretion, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and intrarenal (wedged) venous pressure (IRVP). In comparison with normotensive controls, the exaggerated natriuretic response in hypertensives (P less than 0.05 for UNaV during WI) was associated with an enhanced vasodilating response as demonstrated by a greater increase in ERPF (P less than 0.05) and by a more pronounced fall in calculated renal precapillary resistances (P less than 0.05). A more significant increase in IRVP was found in hypertensive group (P less than 0.05). Glomerular filtration rate (GFR) did not change in either group during WI. MAP, unchanged in normotensives, was significantly reduced in hypertensives (P less than 0.05), while remaining in the hypertensive range. These findings suggest that intrarenal physical factors play a major role in determining the exaggerated natriuresis during WI in hypertensive man.     

Renal hemodynamics and natriuresis during water immersion in normal humans

The renal vascular and functional responses to acute central hypervolemia by water immersion to the neck were determined in six normal subjects. During isotonic-isooncotic expansion by water immersion there was a significant increase in urine flow from 1.1±0.1 to 6.9±1.0 ml/min (p<0.05) and sodium excretion from 99.1±8.8 to 300±28 Eq/min (p<0.05). Glomerular filtration rate did not change while renal blood flow significantly increased during water immersion. Deep intrarenal venous pressure (IRVP) increased from 18.2±1.4 to 32±1.7 mmHg (p<0.05) while mean arterial pressure was unchanged. This marked natriuresis seen during water immersion was associated with reduced renal vascular resistance and increased deep intrarenal venous pressure demonstrating that continued natriuresis could relate to increased capillary hydrostatic pressure.     

Observations on Lipid Metabolism in Chronic Renal Failure, During Conservative and Haemodialysis Therapy

The main variables of glycolipid metabolism (blood non-esterified fatty acids, triglycerides, cholesterol, insulin, glucose) have been measured in basal conditions in ura-emic patients on conservative treatment and on dialysis of different duration and bath glucose concentration (no glucose, 1 g/1, 2 g/1). Basal values for the patients on conservative dietary treatment are not different from normal. In dialysed patients, the blood non-esterified fatty acid and triglyceride concentrations are increased (p < 0.001) while cholesterol glucose and insulin levels are unchanged. No significant difference is found between the various types of dialysis, having different duration and bath glucose concentration.     

Early abnormalities in left ventricular diastolic function of sodium-sensitive hypertensive patients.

The aim of this study was to evaluate whether salt-sensitivity in essential hypertension produces a significant comparative difference in diastolic function and ventricular mass when compared with sodium-resistance. Recent epidemiological data have demonstrated a positive correlation between sodium intake and arterial pressure. Furthermore, a positive correlation has been detected between sodium intake and left ventricular hypertrophy (LVH) independently of arterial pressure. Thirty-one patients who had never been treated before for uncomplicated hypertension were studied. Each subject received a 30 mmol/per day sodium diet for 14 days, supplemented with a further 190 mmol of sodium in the first study week (220 mmol for the first 7 days and 30 mmol for the second 7 days). Throughout the study compliance was assessed by measuring daily urinary sodium excretion. Sodium sensitivity of blood pressure was defined as the difference (5% or more) between blood pressure at the end of the low and high sodium intake periods. On this basis 16 patients were defined as salt-sensitive (SS) and 15 patients as salt-resistant (SR). The two groups were homogeneous for age, sex and race. Baseline mean arterial pressure (MAP) was comparable between SS (108 +/- 1.8 mm Hg) and SR (107 +/- 2.1 mm Hg, P = NS). Each patient was submitted to M-MODE and two-dimensional echocardiogram studies in order to estimate left ventricular mass using the Penn conventional formula and parameters of left ventricular diastolic function. The left ventricular mass measurement showed higher values in the SS group although this did not reach statistical significance (118.4 +/- 4.4 vs 112.0 +/- 4.2 gr/mq, P = NS). Both interventricular septal and posterior wall thickness did not demonstrate significant differences between the two groups. The salt-sensitive group showed impaired left ventricular diastolic function; in particular, the first diastolic peak representing the early maximum of diastolic filling velocity (E) was lower in SS subjects than in SR subjects (71.6 +/- 2.9 vs83.1 +/- 3.3 cm/sec, P < 0.02). No significant difference was detected in the second peak representing the atrial maximum of filling velocity (A) (69.0 +/- 2.3 vs 66.0 +/- 2.0 cm/sec, P = NS). As a consequence the E/A ratio was significantly different (0.73 +/- 0.2 in the SR vs 1.2 +/- 0.04 in the SS group, P < 0.05). Moreover, the peak E integral was lower in SS than in SR subjects (8. 7 +/- 0.6 vs11.2 +/- 0.5 cm, P < 0.005; no difference for the peak A integral (6.0 +/- 0.3 vs 5.7 +/- 0.4 cm, P = NS). The E peak deceleration time was significantly reduced in the SS group (400.3 +/- 13.5 vs 500.9 +/- 12.8 cm/sec, P < 0.001). No significant difference was found for the isovolumetric relaxation time (IVRT) (95.7 +/- 4.3 vs 92.2 +/- 4.0, P = NS). Our data show an impaired diastolic function expressed by a reduced early diastolic filling velocity (peak E) and a significantly abnormal E/A ratio in SS in comparison with SR subjects. Therefore abnormalities in diastolic function are detectable earlier in SS hypertensive subjects than in SR irrespective of actual MAP.     

Cardiovascular,baroreflex and humoral responses in hypertensive patients during nicardipine therapy

Summary Cardiovascular, baroreflex and humoral responses were evaluated in 8 patients with essential hypertension during a control period and then after oral treatment for 5 days with nicardipine hydrochloride 60 mg/d, a calcium channel antagonist.Systolic, diastolic and mean arterial cuff pressures fell after the treatment from 145.7, 98.6 and 114 mmHg control to 136.5, 86.1 and 102.9 mmHg. Heart rate increased from 71 to 78.7 beats/min indicating activation of the baroreflex control mechanism. Neurally mediated changes in the cardiovascular responses to an increase in carotid baroceptor activity and to dynamic exercise were not affected by the drug, nor was the renin-aldosterone system. Thus, a clinically dose of nicardipine significantly reduced mean arterial pressure, whilst preserving circulatory homeostasis.     

Effects of salt sensitivity on neural cardiovascular regulation in essential hypertension

Salt-sensitive hypertensive subjects, as defined by conventional categorical classification, exhibit alterations of autonomic cardiovascular control. The aim of our study was to explore whether, in hypertensive subjects, the degree of autonomic dysfunction and the level of salt sensitivity are correlated even when the latter is only mildly elevated and displays under-threshold values. Salt sensitivity of 34 essential hypertensive subjects was assessed on a continuous basis by the salt sensitivity index after low- and high-sodium diet. Beat-by-beat finger blood pressure was recorded after each diet period. Autonomic cardiovascular control was evaluated by spectral analysis of blood pressure and pulse interval and by assessment of spontaneous baroreflex sensitivity (sequence technique). Salt sensitivity and baroreflex sensitivity showed a negative relationship during low and high sodium intake, starting from low values of the salt sensitivity index. All spectral indexes of pulse interval, except the ratio between low- and high-frequency powers, were inversely related to salt sensitivity index after high sodium intake. In subjects with lower salt sensitivity, baroreflex sensitivity and pulse interval power in the high-frequency band were higher after high sodium intake than after low sodium intake. In contrast, subjects with a higher salt sensitivity index showed lower values of baroreflex sensitivity and pulse interval power in the high-frequency band, uninfluenced by salt intake. Our results provide the first demonstration of an impairment of parasympathetic cardiac control in parallel with the increase in the degree of salt sensitivity, also in subjects who were not ranked as salt-sensitive by the conventional categorical classification.