We determined the antiarrhythmic effect of Rbl (from Panax notoginsengl on different ar rhythmia models and its effect on cytoplasmic Ca2+ concentrations ([Ca2+]i) in rat heart cells with fura-2 fluorescence. At doses of 30 and 50mg/Kg, Rb1 produced an antirrhythmic effect on BaClz-induced ven tricular tachyarrhythmia in rats, atria (fibrillation induced by CaCl2-ACh, and ventricular fibrillation induced by chloroform in mice. The rest [Ca22]i was 108+10.7nM in the freshly isolated rat heart cells. Sixty mM KCl caused an increase in [Ca2+]i to 379.4±77nM. Rb1 from 0.1 to 0.8mM significantly reduced this increase in a concentration-dependent manner, mM Rb1 (0.4mM) also completely inhibited the increase in [Ca2+]i induced by 1 μM isoprenaline. The radioligand binding study in rat heart cells showed that Rb1 did not change the Bmax. and Kd values of [3H]-dihydroalprenolol binding. These data suggest Rb1 can inhibit Ca2+ entry through voltage-dependent and receptor-linked Ca2+ channels, and that this is related to its antiarrhythmic effect, Drug Dev. Res. 39: 179-183.

We examined the endothelium-dependent relaxation response to acetylcholine (Ach) in treptozotocin-induced diabetic rat aorta at the stages of 2- and 6-wks' duration in vitro, and compared with another two groups which were treated with dietary supplement of 0.1% Aminoquanidine (AG) and 0.5% Erigeron breviscapus(EB) from l-week of diabetes induction. At the stage of 2-wks' duration of diabetes, relaxation responses to lower concentrations of Ach in 0.3uM phenylepherineprecontracted aortas were diminished significantly (Pc0.05) compared with agematched control, but the maximal relaxation of Ach remained unchanged. At the stage of 6-wks' duration, diabetes caused an approximately 60% (P<0.001) deficit in maximum relaxation, and this was significantly (P<0.001) prevented in AG and EB treated groups. There was an approximately 40% enhancement in the maximum contractile response to phenylepherine with diabetes (P<0.5), which was unaffected significantly by AG and EB treatments. The data suggest that the defective endothelium-dependent relaxation in diabetic rat aorta occurred as early as 2-wks' duration of diabetes, and the treatments of AG and EB could protect vascular endothelium although the deficits in vascular smooth muscle contractile responses were not protected.

1. The effects of chebulinic acid, which has been shown to elicit blood pressure lowering effect in rats, on aortic vascular contraction as well as cardiac contraction were studied in rats. 2. Chebulinic acid had no effect on KCI-induced aortic contraction, but irreversibly inhibited the contractile responses to phenylephrine in an apparently non-competitive manner. Chebulinic acid also inhibited contractile responses of rat aorta to 5-hydroxytryptamine and angiot ensin It. 3. Chebulinic acid inhibited the binding of pH]-prazosin to dog aortic microsomal membranes in a concentration-depen-dent manner with an IC50 value of 0.3dmmol/L Results of saturation binding experiments suggest a mixed mode of inhibition by chebulinic acid (i.e. a decrease in both the maximal number of binding sites and the affinity for prazosin). 4. Chebulinic acid concentration-dependently and reversihly inhibited the maximal left ventricuiar pressure of rat heart in a Langendorff preparation with 50% inhibition occurring at a concentration of 0.3nmol/L. 5. We conclude that chebulinic acid exerts non-specific inhibitory actions in vascular preparations. Its inhibitory effect on cardiac contraction was reversible and three orders of magnitude more potent than that on vascular contraction. We suggest that the hypotensive effect of chehulinic acid is probably mediated via the decrease in cardiac output resulting from reduced left ventricular contraction.

We studied the Ca2+ movement induced by activation of α1A-, α1B- and α1D-adrenoceptor subtypes in transfected HEK-293 cells with the fura- probe. All these α1-AR subtypes induced both Ca2+ release and Ca2+ entry. The effect on Ca2+ release in α1b transfected HEK-293 cells was bigger than that in α1a and α1b transfected HEK-293 cells, and the effects on Ca2+ entry were the same in ala, alb and aid transfected HEK-293 cells. The Ca2+ entry was inhibited by 1mM NiSO4, but not by nifedipine. Cyclopiazonic acid (CPA) produced a biphasic Ca2+ signal response in Ca2+ medium, and only induced a transient response in Ca2+-free medium. After depletion of CPA-sensitive Ca2+ pool by 10uM CPA in Ca2+-free medium, 10uM adrenaline (Adr) still transiently increased [Ca2+]i in three different α1-adrenoceptor subtype transfected HEK-293 cells. However, after depletion of drenaline-sensitive Ca2+ pool by 10uM Adr, CPA transiently elevated [Ca2+], only in ala and aid transfected HEK-293 cells, not in a,, transfected HEK-293 cells. U73122, a phospholipase C (PLC) inhibitor, inhibited both Ca2+ release and Ca2+ entry induced by activation of α1B-AR,α1B and α1D subtypes in transfected HEK-293 cells. These results suggest that HEK-293 cell line contains two functionally separate intracellular Ca2+ pools, CPA-sensitive and Adr-sensitive pools. Activation of a,,-AR stimulates Ca2+ release from both CPA-sensitive and Adr-sensitive Ca2+ pools. α1A and α1D subtypes induce Ca2+release only from Adr-sensitive Ca2+ pool.

Newborn male Wistar rats were treated with nerve growth factor daily by subcutaneous inJection for 2 weeks, and control rats were treated with either cytochrome c or buffered saline. Average body weight of the treated animals was lower than that of the controls during the 2 weeks of treatment, but became simdar to that of the controls thereafter. Tissue levers of norepinephrine were elevated in the brain, adrenal glands, nlesernteric arteries, and vas deferens of the treated animals immediately after the treatment, but became simliar in the three grcalps 2 weeks after tbe terminndon of tbe treatment. Blood pressure and heart tale were measured beginning at 4 weeks of age until 28 becks, when the rats were sacrificed and the mesenteric arteries sampled for morphometric measurements of vessel wall dimensions. Pretreatrnent with nerve growth fac tor did not affect blood pressure, nor heart rate. Stroctural atteration of the three types of mesenteric arteries was also absent in the treated animals. We conclude that even though neonatal treatment of normal Wistar rats with nerve growth factor for 2 weeks induced an elevation of the norepinephrine levels in severat tissues at the end of the treatment period, it was not sufficient to produce hypertension and structural alterations in the blood vessels.