Fuminori Masugi

Circulating factor with ouabain-like immunoreactivity in patients with primary aldosteronism

Circulating factor with ouabain-like immunoreactivity was studied in patients with primary aldosteronism. Anti-ouabain antibody was prepared from specific pathogen-free rabbits. In the plasma of patients with primary aldosteronism, the level of a factor with ouabain-like immunoreactivity was 2.59 +/- 1.39 pmol ouabain equivalent/ml plasma. This value was significantly (p less than 0.05) higher than that of age-matched normotensive subjects, 1.06 +/- 0.86 pmol ouabain equivalent/ml plasma. The plasma level of ouabain-like immunoreactivity correlated significantly (p less than 0.05) with blood pressure. These results indicate that the factor with ouabain-like immunoreactivity may play a pathophysiological role in the maintenance of the high blood pressure observed in patients with primary aldosteronism.

Effects of 1Oalkyl2acetylsnglycero3phosphocholine (platelet activating factor) on cardiac function in perfused guinea-pig heart

The direct cardiac action of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) was studied in isolated perfused guinea-pig heart preparations. PAF produced a fall in left ventricular pressure, decreases in the rate of rise of the left ventricular pressure (dp/dt) and coronary flow, but had no effect on heart rate. These results indicate that PAF is a cardiodepressant with inotropic selectivity and this effect on heart is blocked by CV-3988, a specific PAF antagonist.

Ouabain-Like and Non-Ouabain-Like Factors in Plasma of Patients with Essential Hypertension

Circulating inhibitor of Na+,K+-ATPase and ouabain-like immunoreactivity were studied in patients with essential hypertension. In the plasma of patients, two types of Na+,K+-ATPase inhibitors (ouabain-like and non-ouabain-like inhibitors) and ouabain-like immunoreactivity were detected. Ouabain-like inhibitor was clearly detected at a low KCl concentration (0.1 mM) in the assay buffer, and non-ouabain-like inhibitor was detected at a high KCl concentration (10 mM). The plasma level of ouabain-like inhibitor correlated significantly with that of ouabain-like immunoreactivity (p less than 0.001) and with a mean blood pressure (p less than 0.01). The plasma level of non-ouabain-like inhibitor was not correlated with the levels of either ouabain-like immunoreactivity or mean blood pressure. The level of plasma ouabain-like inhibitor did not correlate with that of plasma non-ouabain like inhibitor. Both ouabain-like inhibitor and ouabain-like immunoreactivity in the plasma of patients with essential hypertension were significantly higher than those in normotensive subjects, but the plasma level of non-ouabain-like inhibitor in patients with essential hypertension was not higher than that in normotensive subjects. These results suggest that the plasma from patients with essential hypertension contains ouabain-like factor(s) which is important to maintain the high blood pressure.

Effect of 1-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine inhibitor on the reduction of one-kidney, one clip hypertension after unclipping in the rat

The role of 1-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine in regulating blood pressure was studied in one-kidney, one clip hypertensive rats using 3-(N-n-octadecylcarbamoyloxy)-2-methoxypropyl-2-thiazolio ethylphosphate, which specifically inhibited the hypotensive activity of exogenously injected 1-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine. The blood pressure of rats with established hypertension produced by clipping one renal artery and contralateral nephrectomy normally decreases rapidly after unclipping the artery, but this rapid decrease was significantly inhibited by intravenous infusion of 3-(N-n-octadecylcarbamoyloxy)-2-methoxypropyl-2-thiazolio ethylphosphate. This shows that endogenous 1-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine participates in the rapid decrease of blood pressure after unclipping the kidney in one-kidney, one clip hypertensive rats.

Effects of ouabain on blood pressure regulation in rats

In order to test the hypothesis that a circulating inhibitor of the sodium-potassium ATPase pump may cause a concomitant rise in blood pressure and increased sodium excretion, we studied chronic effects of continuous infusion of ouabain, an inhibitor of sodium-potassium ATPase, for up to 6 days on systolic blood pressure and urinary sodium excretion in conscious rats. We also evaluated the effect of this substance in rats with hypertension induced by chronic infusion of norepinephrine. Continuous infusion of ouabain (1.2 mg/kg per day) into the jugular vein by an osmotic minipump did not induce any changes in systolic blood pressure and urinary sodium excretion in intact rats on regular diets. Furthermore it did not cause a change in systolic blood pressure in rats drinking 1% NaCl, and in unilaterally nephrectomized rats drinking 1% NaCl, when compared with vehicle-infused animals. When the same dose of ouabain was administered simultaneously with 1.8 mg/kg per day norepinephrine infused intraperitoneally by another osmotic minipump in conscious rats, systolic blood pressure rose on day 1 to only 129.3 +/- 2.8 mmHg compared with the rist to 145.0 +/- 2.0 mmHg when norepinephrine alone was infused (P less than 0.01). The antihypertensive effect of ouabain was sustained for the entire experimental period lasting for 6 days and was not associated with any changes in urinary sodium excretion. The administration of ouabain to rats made hypertensive by a 3-day infusion of norepinephrine, returned the blood pressure to control levels, and the antihypertensive effect was sustained throughout the experimental period lasting a further 3 days and was not associated with any changes in urinary sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Potent hypotensive activity of 1-O-hexadecyl-2-O-acetyl-sn-glycero-3-phosphocholine in spontaneously hypertensive rat

Abstract Chemically synthesized 1-O-hexadecyl-2-O-acetyl- sn -glycero-3-phosphocholine possessed the most potent hypotensive activity compared with bradykinin, prostagrandin E 2 and I 2 when 5 nano moles/kg body weight of each drug were administered intravenously in spontaneously hypertensive rat. The potency and the duration of hypotensive activity of 1-O-hexadecyl-2-O-acetyl- sn -glycero-3-phosphocholine were dose dependent. Exogenous norepinephrine or angiotensin II showed pressor activity during the hypotensive action of 1-O-hexadecyl-2-O-acetyl- sn -glycero-3-phosphocholine, but did not disturb the hypotensive pattern of this ether lipid. These may suggest that 1-O-alkyl-2-O-acetyl- sn -glycero-3-phosphocholine plays an important role for the regulation of blood pressure.

Autoimmune neutropenia with anti-neutrophil autoantibody associated with Sjögren's syndrome.

A 74-year-old man developed neutropenia in association with Sjögrens syndrome. The peripheral neutrophils in his blood decreased to 210/mm3 (total white blood cell count 2,100/mm3). Bone marrow examination showed an increase in the number of neutrophil precursors. The presence of anti-neutrophil autoantibody (ANAB) in his plasma was determined by an enzyme-linked immunosorbent assay. Prednisolone therapy resulted in an increase in the neutrophil count and a decrease in the ANAB titer. However, when the daily dose of prednisolone was decreased, the neutrophil count gradually decreased, and the ANAB titer increased again. These results suggest that neutropenia in this patient was caused by ANAB, and ANAB could be the result of autoimmune disorders associated with Sjögrens syndrome.

Hypotensive mechanism of acetyl glyceryl ether phosphorylcholine (AGEPC) in dogs. Effects on hemodynamics and humoral factors

One-O-hexadecyl-2-O-acetyl-sn-glycero-3-phosphorylcholine (AGEPC) was intravenously administered to anesthetized dogs to study the effects on hemodynamics and several endocrine factors. The effect of AGEPC on local blood flow was also studied by direct intra-arterial injection. Following intravenous injection, blood pressure and cardiac output decreased significantly (p less than 0.001). Changes in total peripheral resistance (TPR) and heart rate were biphasic. TPR increased significantly (p less than 0.01) after an initial slight reduction. Heart rate decreased significantly (p less than 0.01) with only a transient slight elevation. Femoral blood flow was increased (p less than 0.001) by intraarterial injection and decreased (p less than 0.05) by intravenous administration. Plasma norepinephrine (p less than 0.001), epinephrine (p less than 0.01), thromboxane B2 (p less than 0.001), 6-0-PGF1 alpha (p less than 0.01), aldosterone (p less than 0.001) and cortisol (p less than 0.001) were elevated, but plasma renin activity did not change. These results suggest that the hypotensive mechanism of AGEPC is due to both cardiosuppression and vasodilation. AGEPC increased plasma catecholamines, thromboxane A2, PGI2, aldosterone and cortisol which, in turn, may modify hemodynamics.

Endogenous platelet-activating factor and anti-platelet-activating factor in patients with renovascular hypertension

Renovascular hypertension is relieved by percutaneous transluminal renal angioplasty. In four patients with renovascular hypertension, platelet-activating factor (PAF) was found to be released into the ipsilateral renal venous blood after percutaneous transluminal renal angioplasty, but was not found in the contralateral renal venous blood following this procedure. Anti-platelet-activating factor with a lipid-like property was also found, and its polarity was slightly lower than that of PAF judging by its behavior on thin layer chromatography. Anti-platelet-activating factor completely blocked the aggregation of rabbit platelets induced by PAF, ADP or arachidonic acid. These results indicate that PAF and anti-platelet-activating factor are released into renal venous blood following percutaneous transluminal renal angioplasty in patients with renovascular hypertension.

Partial purification and properties of a plasma ouabain-like inhibitor of Na+, K+-ATPase in patients with essential hypertension.

Plasma levels of an ouabain-like inhibitor of Na+,K+-ATPase were higher in patients with essential hypertension compared with normal levels. The ouabain-like inhibitor was correlated significantly with blood pressure and was increased by a high-salt diet. The substance was partially purified by high performance liquid chromatography which revealed lipid-like properties, but the elution time was different from that of free unsaturated fatty acid on silica-gel high performance liquid chromatography. Its molecular weight was 600 or less, as estimated by high performance liquid chromatography with an HSG-15H column. The ouabain-like substance inhibited Na+,K+-ATPase in competition with KCI and showed positive ouabain-like immunoreactivity, whereas lysophosphatidylcholine was a non-competitive inhibitor. The ouabain-like substance was unstable at room temperature and decomposed to smaller molecular compounds which did not inhibit Na+,K+-ATPase. The inhibitory fraction gave a positive thiobarbituric acid reaction test. The mobility of the ouabain-like inhibitor on silica-gel thin-layer chromatography was different from that of prostaglandins and arachidonic acid. These results indicate that the plasma ouabain-like inhibitor of patients with essential hypertension is a lipid which is different from free fatty acid or lysophosphatidylcholine, and may be an unstable peroxide.