[Effect of palonidipine hydrochloride (TC-81), a new dihydropyridine derivative, on various myocardial ischemic models].

The antianginal effects of palonidipine, a novel 1,4-dihydropyridine derivative, and nifedipine on various myocardial ischemic models were compared. (1) Palonidipine at 0.5 mg/kg, p.o. significantly inhibited vasopressin-induced ST depression of ECG in Donryu rats. This activity was about 5 times more potent than that of nifedipine and was long-lasting. (2) Palonidipine at 1 mg/kg, i.d. significantly inhibited ST depression induced by isoproterenol in Wistar rats. This activity of TC-81 was more potent than that of nifedipine. (3) Palonidipine at 3 micrograms/kg, i.v. produced an increase in regional myocardial tissue blood flow in the ischemic region of chronic coronary artery occluded dogs. (4) In isolated dog coronary artery, palonidipine at a concentration of 10(-10) M or greater inhibited the amplitude of 3,4-DAP-induced cyclic contractions in a concentration-dependent manner. This activity was 10-30 times more potent than that of nifedipine. (5) An intracoronary injection of endothelin (30 pmol/kg) reduced the coronary blood flow, subepicardial tissue blood flow, and subepicardial pH in anesthetized dogs. The ST elevation of ECG over 0.1 mV also occurred in 8 of 10 cases. In all the cases, ventricular extrasystoles were noted, and 9 out of 10 animals died. Pretreatment with palonidipine (3 micrograms/kg, i.v.) inhibited endothelin-induced ischemic changes, with a potency greater than that of nifedipine. These results suggest that palonidipine may be useful for the therapy of angina-pectoris.

Inhibition of prostaglandin synthesizing enzymes by haptoglobin and plasma of rats with inflammation.

Administration of carrageenin or adjuvant to rats to induce inflammation produced increases in the plasma haptoglobin level. Simultaneously, there was an increase in the activity of the plasma inhibitor of prostaglandin E2 synthesis. Partially purified haptoglobin inhibited the microsomal over-all conversion of arachidonic acid to prostaglandin E2. The addition of the haptoglobin inhibited two heme-dependent reactions catalyzed by a purified enzyme of seminal vesicle microsome, i.e., the prostaglandin G2 synthesis from arachidonic acid and the conversion of prostaglandin G2 to H2. However, the plasma inhibitory activity was accounted for only partially by the haptoglobin contained in the plasma from treated rats.

[Biological activity of 1alpha-hydroxycholecalciferol (II). Effect on the metabolism of calcium and phosphorus in rats (author's transl)].

Effect of 1alpha-hydroxycholecalciferol on the metabolism of calcium and phosphorus was studied using Ca-labelled and non-labelled rats. With an oral daily dose of 2.5 or 12.5 microgram/kg of 1alpha-hydroxycholecalciferol, serum calcium, urine volume, urinary calcium excretion, urinary calcium concentration and water consumption increased, while fecal concentration, urinary phosphorus concentration and food consumption decreased. There was a lag time (1 or 2 days) between the increase of serum calcium and that of specific activity of serum calcium, and bone resorption was stimulated later than was intestinal calcium transport. After 10 days treatment, calcium concentration in the femur decreased, while a remarkable calcification was noted in soft tissues such as kidney, intestine, aorta, heart and muscle, although these effects were reduced with lower doses of the drug. With a smaller oral daily dose (0.1 or 0.5 microgram/kg), for 6 months, bone calcium and phosphorus concentration increased without soft tissue calcification. Thus, 1alpha-hydroxycholecalciferol may be an effective drug for patients with metabolic bone diseases.