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Two forms of renin, one of mol.wt. 43,000 and the other 60,000, were found in the dog kidney. Conversion between the two forms of renin was reversible at neutral pH. Though the molecular weight of renin in kidney-cortex homogenate was 43,000, it was completely converted into high-molecular-weight renin in the presence of substances that react with thiol groups. On the contrary, stored renin in the granules was the form of normal size (mol. wt. 43,000) regardless of the absence or presence of such substances. The present experiments indicated that renin is stored in the granules as the form of normal size and might be converted into high-molecular-weight renin when it is released from the granules and attached to some substance in the soluble fraction of renal-cortical tissue.

1. Renal cortical homogenates of the dog were subjected to sieve separation, a Nucleopore Filter being used to separate the renin granules. 2. The molecular weight of renin in the granules was estimated to be about 40 000 by gel filtration. Renin was converted into a higher-molecular-weight form (60 000) by mixing with cytosol in the presence of sodium tetrathionate, a thiol inhibitor. 3. When cytosol was pretreated with acid (pH 3.0) or heating (100 degrees C), the molecular-weight conversion did not occur. 4. Cytosol was separated into three parts by gel filtration. Fraction A included substances with a molecular weight of over 47 000, fraction B from 47 000 to 32 000, and fraction C from 32 000 to 15 000. The mixture of renin in the granules with fraction A and sodium tetrathionate resulted in the formation of a higher-molecular-weight form of the enzyme, but no change in molecular weight was detected when renin was mixed with fractions B or C and sodium tetrathionate.

S-2150 is a new 1,5-benzothiazepine derivative that inhibits [3H]diltiazem and [3H]WB4101 bindings to the membrane of rat tissue. The effects of S-2150 on ischemia/ reperfusion injury were studied in anesthetized rats. S-2150 reduced the myocardial infarct size (IS) induced by 20-min coronary artery occlusion followed by reperfusion. To evaluate reperfusion-induced ventricular tachycardia and fibrillation (VT, VF), we occluded the coronary artery for 4 min and then reperfused it. The incidence of arrhythmia was blocked by S-2150, and this effect offered protection against cardiac death. Prazosin did not modify the IS or incidence of reperfusion arrhythmias, but combined treatment with a noneffective dose of diltiazem showed significant cardioprotective effects. We also compared the direct effects of S-2150 and diltiazem on cardiac function and coronary perfusion flow using isolated rat hearts. Both drugs decreased mechanical function and increased coronary flow, with S-2150 being less cardiodepressive and more vasodilatory. S-2150 is cardioprotective at doses comparable to hypotensive doses even though its cardiodepressant effect is much weaker than that of diltiazem. This effectiveness may be partly explained by its dual characteristics: blocking the Ca channel and the alpha 1-adrenoceptor.

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