|Budget Amount *help
¥1,500,000 (Direct Cost : ¥1,500,000)
Fiscal Year 1991 : ¥300,000 (Direct Cost : ¥300,000)
Fiscal Year 1990 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Studies on the mechanism of magnesium lithospermate B, which is a newly found constituent of Salviae Miltiorrhizae Radix, were performed. It was found that the renal function-faciltating action of magnesium lithospermate B was eliminated by indomethacin, suggesting that this compound acts on the prostaglandin system. Indeed, magnesium lithospermate B increased urinary excretions of prostaglandin E_2 (PGE_2) and 6-keto-prostaglandin F_<1alpha> (6-keto-PGF_<1alpha>). Furthermore, the effect of magnesium lithospermate B on the renal responses of rats with renal failure was investigated in the presence and absence of pretreatment with the kallikrein inhibitor, aprotinin. Pretreatment with aprotinin abolished the renal function-facilitating action of magnesium lithospermate B concomitantly with a markedly increased urinary excretion PGE_<2'> 6-keto-PGF_<1alpha> and kallikrein. In addition, the combination of magnesium lithospermate B and kininase II inhibitor, captopril, induced a further increase in renal function by improving the renal circulatory state. These results suggest that the kallikrein-kinin-prostaglandin system is involved in the renal responses elicited by magnesium lithospermate B.
We also evaluated the antihypertensive effect of magnesium lithospermate B in rats with sodium-induced hypertension and renal failure. It was found that administration of magnesium lithospermate B produced a significant reduction in blood pressure, accompanied by a significant increase of urinary sodium, PGE_2 and kallikrein excretions. The same results were demonstrated by the experiment using spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY) and deoxycorticosterone acetate (DOCA) rats.