Takashi Mandai

Simple method for the simultaneous determination of noradrenaline, dopamine and serotonin by stepwise elution from a short column of weak cation-exchange resin

A simple method for the simultaneous determination of noradrenaline, dopamine and serotonin using a short column of Amberlite CG-50 is described. Noradrenaline and dopamine were eluted from the column with phosphate buffers containing 1.5 and 4.0% boric acid, respectively, and then serotonin was eluted with 1.0 N HCl. Catecholamines were determined by a modification of the ethylenediamine condensation method using potassium ferricyanide as oxidant and isobutanol for extraction of the fluorophores. Serotonin was measured by the acidic o-phthalaldehyde method. The method was applied to the simultaneous determination of noradrenaline, dopamine and serotonin in discrete regions of rat brain.

Effects of two angiotensin II analogues on blood pressure in normal subjects with various sodium balances

Abstract The antagonistic potencies and agonistic effects of two clinically available angiotensin II analogues, 1-sarcosine, 8-isoleucine angiotensin II and 1-sarcosine, 8-alanine angiotensin II, were compared in normal subjects in various sodium balances. Both compounds had an agonistic pressor effect and this was affected by the sodium balance; in the low sodium state, the agonistic effect of both compounds decreased significantly and that of 1-Sar,8-Ala angiotensin II was not seen. The agonistic effect of 1-Sar,8-Ile angiotensin II was greater than that of 1-Sar,8-Ala angiotensin II in all sodium balances. The antagonistic effects of both compounds were also affected by the sodium balance, and were greatest in the low sodium state. In subjects on low sodium diet or regular diet 1-Sar,8-Ile angiotensin II had the same or more antagonistic action than 1-Sar, 8-Ala angiotensin II, but in those on high sodium diet the reverse was observed. In clinical and pharmacological studies, the sodium balance of patient should always monitored. Pretreatment of patients for sodium depletion is necessary to prevent side effects due to the agonistic pressor effects of these compounds.

Sodium depletion and blood pressure response to 1‐sarcosine, 8‐isoleucine angiotensin II in hypertension

The relation of sodium balance to the blood pressure response to 1‐sarcosine, 8‐isoleucine angiotensin II ([Sar1, Ile8]AII) was evaluated in patients with hypertension of various causes. Tests with [Sar1, Ile8]AII were made under the following three conditions: (1) unrestricted diet and no diuretic pretreatment, (2) unrestricted diet and 40 mg furosemide intravenously 2 hr before the test, and (3) mild salt restriction (5 gm NaCl/day) and 80 mg furosemide orally for 3 days before the test. Among patients with renovascular or malignant hypertension, 5 of 14 cases (36%) in condition 1, 3 of 6 cases (50%) in condition 2, and 7 of 7 cases (100%) in condition 3, there was a reduction of more than 10 mm Hg in the mean blood pressure. The pressor responses in essential hypertension and in primary aldosteronism were reduced by sodium depletion. All patients with pressor responses of over + 10 mm Hg in condition 3 were patients with primary aldosteronism. These results indicate that before the [Sar1, Ile8]AII test sodium depletion is useful not only for preventing an excessive pressor response in low reninemic patients but also for increasing the specificity of the test in the evaluation of renin‐dependent hypertension. Angiotensin II‐inhibiting analogues are useful in the detection of abnormally high or abnormally low renin levels.

Comparison of the biological effects of two angiotensin II analogues in hypertensive patients with sodium depletion

Abstract The effects on blood pressure (BP), plasma aldosterone concentration (PAC) and plasma renin activity (PRA) of two angiotensin II analogues (AII A), i.e., 1-sarcosine, 8-isoleucine angiotensin II (Sar 1 , I1e 8 -AII) and 1-sarcosine, 8-alanine angiotensin II (Sar 1 , Ala 8 -AII), were investigated in patients with hypertension with various etiologies on sodium depletion. The changes of BP, PAC and PRA on infusion of Sar 1 , Ile 8 -AII and Sar 1 , Ala 8 -AII were very similar. With both compounds, there were significant inverse correlations between the pre-infusion PRA and the changes in BP and PAC, and a significant positive correlation between the pre-infusion PRA and change in PRA. The slopes of the regression lines for the correlations of changes in BP, PAC and PRA, plotted as functions of the pre-infusion PRA for Sar 1 , Ile 8 -AII and Sar 1 , Ala 8 -AII were not statistically different. In clinical investigations, the two compounds seemed equally useful for detecting renin-dependency in hypertension.

Effects of Two Angiotensin II Analogues on Blood Pressure, Plasma Aldosterone Concentration, Plasma Renin Activity and Creatinine Clearance in Normal Subjects on Different Sodium Intakes

SummaryTwo angiotensin II analogues (AIIA), 1-sarcosine, 8-isoleucine angiotensin II ([Sar1, Ile8]-AII) and 1-sarcosine, 8-alanine angiotensin II ([Sar1, Ala8-AII), were infused in six normal volunteers on high, regular and low sodium diets. The agonist and antagonist activities of these AIIA on blood pressure (BP), plasma aldosterone concentration (PAC), creatinine clearance and plasma renin activity were examined. Both AIIA had agonistic pressor activities in subjects on high and regular sodium diets, [Sar1, Ile8]-AII being more potent than [Sar1, Ala8]-AII. Both AIIA caused similar elevation of PAC in subjects on high and regular sodium diets, and an equally fall in PAC in subjects on a low sodium diet. Both AIIA strongly antagonized the rise in BP, the increase in PAC and the reduction of Ccr induced by AII administration in subjects on all three sodium diets. The results indicate that both AIIA can be used to examine the activity of the renin-angiotensin system in patients with hypertension, and they also suggest that AII interaction with its receptors differs in different target tissues.

Urinary Catecholamine Response to Glucagon in Young and Elderly Patients with Essential Hypertension

本態性高血圧症, 血圧維持機構における交感神経系の関与が注目されている. しかし, 多種の要因が複雑に関与しているため現在のところ明確な結論は得られていない. 今回, 本態性高血圧症における加齢による交感神経系の関与の差異を検索するため, グルカゴン負荷時の尿中カテコールアミン反応性 (尿中アドレナリンおよびノルアドレナリン排泄値) を指標とすることにより, 老年性および若年性本態性高血圧症の交感神経系機能を比較検討した. その結果, 1) 若年性本態性高血圧症患者において, 交感神経系の反応性亢進をみたが, 2) 老年性本態性高血圧症患者においては, 交感神経系の反応性亢進は認められなかった. また, 3) 若年性および老年性の正血圧者群においては, 交感神経系反応性に有意な差異が認められず, 今回の実験に関する限り, 正血圧者群における加齢による交感神経系の反応性変化は認められなかった. 以上の結果より, 本態性高血圧症における病因としての交感神経系の関与は, 若年性本態性高血圧症では強く疑われたが, 老年性本態性高血圧症においては認める事ができなかった.