No abstract

With the increasing demand for instant real‐time ultrasound (US) imaging of a specific organ, target‐specific and long‐circulating ultrasound contrast agents are of special interest. A new species of echogenic hyaluronic acid nanoparticles is presented as an ultralong‐acting, liver‐specific, US contrast agent that is distinct from conventional gas‐filled microbubbles. Using an oil‐in‐water (O/W) emulsification method, bioinert and hydrophobic perfluoropentane (PFP) is encapsulated as an ultrasound gas precursor into hyaluronic acid nanoparticles (HANPs) using hydrophobic interactions. HANPs are formulated by self‐assembly, with amphiphilic hyaluronic acid‐5β‐cholanic acid (HA‐CA) conjugating in aqueous conditions. The resulting echogenic PFP‐encapsulated HANPs (Echo‐NPs) show solid nanostructures, differentiated from core‐empty conventional microbubbles, and exhibiting outstanding physical properties as an ultrasound contrast agent. They are more stable and robust echogenic solid bodies with an in vivo favorable hydrodynamic size and because PFPs vaporize gradually, their expansion process is very slow in body conditions. After several systemic circulations, echo‐NPs generated intense and ultralong echo signals for US imaging at the target site. The echogenic properties of Echo‐NPs show a significantly increased half‐life and echo persistence, compared with conventional microbubbles. The results clearly show that echo‐NPs outperform conventional microbubbles in terms of both physical and echogenic in vitro and in vivo properties.

To evaluate the antihypertensive effect of magnesium lithospermate B isolated from Salviae miltiorrhizae radix, determinations of blood pressure and urinary excretions of sodium, potassium, prostaglandin E₂ (PGE₂) and kallikrein, which have been proposed to play an important role in the regulation of blood pressure, were made in rats with sodium-induced hypertension and renal failure. In rats given magnesium lithospermate B, blood pressure was significantly decreased, whereas urinary excretion of electrolytes was significantly increased. Urinary PGE₂ excretion following administration of magnesium lithospermate B increased as the dose of the compound was stepped up. The activity of kallikrein in urine was also increased by the treatment. From these results, the blood pressure-lowering action of magnesium lithospermate B may be due in part to enhancement of the kallikrein-prostaglandin system.

Magnesium lithospermate B and adenine were given simultaneously to rats p.o. in order to investigate their renal effects. In rats given magnesium lithospermate B at a dose of 5 mg/kg body weight/day for 12 or 24 days, glomerular filtration rate, renal plasma flow and renal blood flow were increased significantly. A significant increase in renal function parameters was also found in rats given 10 mg of magnesium lithospermate B. Urinary excretion of prostaglandin E₂ was increased by administration of magnesium lithospermate B, while those of 6-keto-prostaglandin F_1α and thromboxane B₂ were unaffected at a dose of 5 mg or 10 mg/kg body weight/day for 12 or 24 days. The activity of kallikrein in urine increased markedly and significantly in rats given 5 or 10 mg of magnesium lithospermate B for 12 or 24 days. From these results, it seems that magnesium lithospermate B increases renal function by improving the renal circulatory state through activation of kallikrein and promotion of prostaglandin E₂ production.