Tetsuji Shingu

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 free calcium and magnesium and calcium-regulating hormones with sodium chloride loading in patients with essential hypertension

This study was designed: (1) to test the hypothesis that the pressor response to sodium chloride loading in patients with essential hypertension is associated with disorder of divalent cations (calcium and magnesium); and (2) to clarify the relationship between intracellular free calcium concentration and serum levels of calcium-regulating factors and intracellular magnesium concentration. With sodium chloride loading, mean blood pressure, urinary calcium and magnesium excretions and platelet calcium concentration were increased, and serum total and ionized calcium, magnesium concentrations and erythrocyte magnesium concentration were decreased. Change in mean blood pressure was correlated with changes in parathyroid hormone (r = 0.49, P less than 0.05), serum total and ionized calcium (r = -0.50, P less than 0.05) and erythrocyte magnesium (r = -0.56, P less than 0.05) and platelet calcium concentrations (r = 0.46, P less than 0.05). In addition, change in platelet calcium concentration was related to changes in parathyroid hormone (r = 0.44, P = 0.05), serum total and ionized calcium (r = -0.66, P less than 0.01) and erythrocyte magnesium concentration (r = -0.49, P less than 0.05). It is concluded that the pressor effect of excessive sodium chloride intake on blood pressure in patients with essential hypertension is associated with a disorder of divalent cations and that alteration of the intracellular free calcium concentration with sodium chloride loading may occur through handling of serum total and ionized calcium, parathyroid hormone and/or intracellular magnesium concentration.

Angiotensin-converting enzyme insertion/deletion genotype is associated with the activities of plasma coagulation factor VII and X independent of triglyceride metabolism

Background The D allele of angiotensin‐converting enzyme (ACE) insertion/deletion (I/D) polymorphism and coagulation activity play important roles in cardiovascular events, however, the precise association between these two risk factors remains unclear. Methods We identified the ACE I/D genotype and measured the plasma coagulation factor VII and X (FVII and FX) activities and serum lipids in 172 patients (110 men and 62 women, mean age 56.7 ± 13.3 years) undergoing coronary angiography. Results The frequency of the D allele was significantly higher in those with a history of myocardial infarction (MI) than in those with normal coronary arteries, but there was no significant association between FVII and FX activities and the stage of coronary disease. Plasma coagulation factor VII and FX activities were significantly lower in the DD genotype (n=42) than in the II genotype (n=67, P<0.001 and P<0.001, respectively) or the ID genotype (n=63, P<0.01 and P<0.05, respectively). The association of the ACE D allele with lower activities of FVII and FX was also seen in patients with coronary artery disease (CAD). There was a significant association between serum triglyceride levels with FVII and FX, but not with the ACE I/D genotype. Conclusion We concluded that the ACE I/D polymorphism may contribute more to the onset of MI than the activities of FVII and FX and that the ACE D allele might be associated with lower plasma activities of FVII and FX. The potential link between ACE I/D polymorphism and the plasma activities of FVII and FX is probably independent of triglyceride metabolism. Coron Artery Dis 14:285‐291 • 2003 Lippincott Williams & Wilkins.

Role of intracellular cation abnormalities in development of left ventricular hypertrophy

To elucidate factors determining the development of left ventricular hypertrophy, we performed measurements of intraerythrocyte sodium and intraplatelet calcium concentrations, measurements of plasma and urinary catecholamine levels and plasma renin activity, calculation of left ventricular mass using echocardiography, and 24-h ambulatory blood pressure (BP) monitoring. The results indicate that abnormalities of sodium and calcium mobilization may play an important role in the adaptation of left ventricular muscle to a persistent increase in BP.

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.

Effect of salt loading on intracellular sodium concentration in erythrocytes and lymphocytes of patients with essential hypertension.

本態性高血圧症患者50例を対象に赤血球およびリンパ球の細胞内Na濃度を,減塩食および増塩食摂取下に測定し,両者の変化の関係および血圧変化との関係を検討した.血圧と赤血球およびリンパ球内Na濃度は,増塩により有意に増加した.赤血球とリンパ球の細胞内Na濃度は減塩期,増塩期とも相関しなかったが,増塩による両者の変化率は有意の正相関を示した.平均血圧の変化率は赤血球およびリンパ球の細胞内Na濃度変化率とおのおの有意の正相関を示した.以上より,増塩による細胞内Na濃度変化は異なる細胞においても共通であること,および本態性高血圧症患者の食塩感受性には細胞内Na濃度変化が関与していることが示唆された.