Koji Kido

Role of cellular calcium in salt sensitivity of patients with essential hypertension.

The mechanism by which excessive sodium chloride intake raises blood pressure has not been fully clarified. The present study was therefore undertaken in patients with essential hypertension to investigate the possible role of an intracellular calcium-dependent mechanism in salt sensitivity. The difference in mean blood pressure between a week of low sodium chloride diet (3 g/day) and a week of high sodium chloride diet (20 g/day) was studied in relation to the intracellular free calcium concentration in lymphocytes and an acute hypotensive response to a 10-mg sublingual dose of nifedipine in 12 inpatients. Sodium chloride loading induced significant increases in mean blood pressure (from 111 ± 12 to 122 ± 11 mm Hg; p < 0.01), intracellular free calcium in lymphocytes (from 133 ± 13 to 145 ± 9 nmol/L;/K0.01), and the hypotensive response to nifedipine (from 19 ± 6 to 31 ± 10 mm Hg;/X0.01). In addition, serum total calcium concentration was decreased while urinary calcium excretion was increased. The elevation of mean blood pressure was closely and positively correlated with the increase in intracellular free calcium concentration (r=0.71, p < 0.05) and the increase in the hypotensive effect of nifedipine (r=0.91, p < 0.01) after sodium chloride loading. However, changes in these values had no relation to the change in serum concentration or urinary excretion of calcium. These data suggest that change in the cellular calcium-dependent vasoconstriction mechanism may be associated with salt sensitivity of patients with essential hypertension.

Intralymphocytic sodium and free calcium and plasma renin in essential hypertension.

Intraceilular sodium, potassium, and free calcium concentrations were investigated in lymphocytes of 30 patients with essential hypertension and 30 normotensive controls. All subjects were placed on a diet containing 8 to 10 g of sodium chloride per day. Lymphocyte sodium concentration was higher in hypertensive patients than in normotensive controls (19.8 ± 1.8 vs 18.4 ± 1.8 mmol/kg wet weight; p < 0.01), whereas lymphocyte potassium concentration was similar in both groups. Lymphocyte free calcium concentration was also higher in hypertensive patients than in normotensive controls (134.6 ± 13.2 vs 120.2 ± 16.4 nmol/L; p < 0.01). There was a positive correlation between lymphocyte sodium and free calcium concentrations in normotensive controls, in hypertensive patients, and in the subjects combined (r = 0.59, p < 0.01; r = 0.71, p < 0.001; and r = 0.70, p < 0.001, respectively). Lymphocyte potassium concentration was not related to lymphocyte sodium or free calcium concentration in each group. In patients with essential hypertension, intraceilular sodium and free calcium concentrations were negatively correlated with plasma renin activity (r = −0.66, p < 0.001; r = −0.60, p < 0.001, respectively), but they were not related to age, mean blood pressure, serum electrolyte concentration, or plasma norepinephrine concentration. These results suggest that a considerable relationship exists between intraceilular sodium and free calcium in lymphocytes and that, in essential hypertension, the alteration in cellular metabolism of sodium and calcium may be linked to the renin system but not to blood pressure, age, or adrenergic activity.

Factors determining sodium chloride sensitivity of patients with essential hypertension: evaluation by multivariate analysis

Factors which determine sodium chloride sensitivity, defined as the difference between the mean blood pressure after 1 week of a low sodium chloride diet (3 g/day) and that after 1 week of a high sodium chloride diet (20 g/day), were studied in 60 inpatients with essential hypertension using a multivariate analysis. The sodium chloride sensitivity was independently correlated with the change in erythrocyte sodium concentration (r = 0.47) and with the change in plasma renin activity (r = 0.29); but it was not related to basal blood pressure, the change in plasma volume of the change in plasma norepinephrine concentration. These data suggest that both intracellular sodium accumulation and inadequate suppression of the renin-angiotensin system may be independently involved in the elevation of blood pressure after sodium chloride loading. We could not find the independent importance of volume retention, hyperadrenergic activity or basal blood pressure in the sodium chloride sensitivity.

Significance of Intracellular Cations and Calcium-Regulating Hormones on Salt Sensitivity in Patients with Essential Hypertension

Although the existence of salt sensitivity in essential hypertensives has been well known, the precise mechanism(s) has not yet been elucidated. The aim of this study was to clarify the relation between the responses in blood pressure, extra- and intracellular cations and calcium-regulating hormones to oral NaCl loading in essential hypertensives. After oral NaCl loading, mean blood pressure, urinary excretions of calcium and magnesium, and PLT[Ca2+]i were significantly increased. [Ca2+]o and E[Mg]i were decreased. The changes (delta) in mean blood pressure by NaCl loading positively correlated with delta PLT[Ca2+]i and delta PTH, and negatively with delta[Ca2+]o and delta E[Mg]i. Delta PLT[Ca2+]i positively correlated with delta PTH and negatively with delta[Ca2+]o and delta E[Mg]i. From these results, the blood pressure response to oral NaCl loading is associated with the alternation of [Ca2+]i metabolism in which the changes in magnesium metabolism and calcium-regulating hormones may be involved.

Relationship of cellular calcium to salt sensitivity in patients with essential hypertension.

The significance of cellular calcium metabolism and systemic calcium balance in sodium chloride sensitivity was studied in 16 patients with essential hypertension and in 13 normotensive subjects. With changes in sodium chloride intake from 3 to 20 g/day, mean blood pressure, lymphocyte [Ca2+]i and the acute hypotensive response to nifedipine were increased in the hypertensive patients, but not in the normotensive subjects. Serum calcium concentration was decreased and urinary calcium excretion was increased in both groups. In the hypertensive patients, elevation of mean blood pressure was positively correlated with the increase in lymphocyte [Ca2+]i and with the enhancement of the hypotensive response to nifedipine, but it was not related to the change in serum or urinary calcium. These results suggest that enhancement of cellular-calcium-dependent vasoconstriction may lead to increased blood pressure following sodium chloride loading in patients with essential hypertension.

Role of Intracellular Free Calcium in the Hypotensive Response to Nifedipine

The acute antihypertensive effect of 10 mg of sublingual nifedipine was investigated in patients with essential hypertension in comparison with that in normotensive controls and in relation to intracellular free calcium concentration ([Ca2 +]i) in lymphocytes. Parameters predictive of the response to nifedipine such as age, pretreatment blood pressure, plasma norepinephrine concentration and plasma renin activity were also assessed. The fall in mean blood pressure with nifedipine was greater, and [Ca2+]i in lymphocytes was higher in patients with essential hypertension than in normotensive controls. In patients with essential hypertension, the hypotensive response to nifedipine was positively correlated with lymphocyte [Ca2+]i (r = 0.82) and negatively linked with plasma renin activity (r = -0.65), but unrelated to age, pretreatment mean blood pressure or plasma norepinephrine concentration. [Ca2+]i in lymphocytes was inversely correlated with plasma renin activity (r = -0.66). In normotensives, the mean blood pressure response to the drug had no relation to the variables studied. These results suggest that the acute hypotensive response to nifedipine may involve [Ca2+]i abnormalities and that calcium-influx-dependent vasoconstriction may be enhanced in essential hypertensive patients with suppressed plasma renin activity.