Previous studies confirmed that the methanolic extract from Curcuma longa L. (CLME) lowers arterial blood pressure and heart rate in rats due to the blockade of extracellular Ca2+ influx. The aim of this study was to investigate the involvement of Na+-Ca 2+ exchanger in the vasorelaxant effects elicited by CLME in isolated rat superior mesenteric arteries. CLME (1-1,000 μg/ml) concentration-dependently relaxed phenylephrine (PHE) (10 μM) pre-contracted arterial rings with intact-endothelium (pD2 and Emax = 2.04 ± 0.06 and 88.3 ± 3.2%) or denuded-endothelium (pD2 and Emax = 2.06 ± 0.03 and 91.4 ± 1.0%), respectively, suggesting that the removal of endothelium has no significant effect (P>0.05) on the vasorelaxation induced by CLME. Furthermore, CLME (30, 100 and 300 μg/ml) inhibited the cumulative concentration-response curves to PHE (10-8-10-5 M) in a concentration-dependent manner, whereas, treatment with ouabain 100 μM (selective blocker of Na+-K+ ATPase) has no effect on the relaxant responses of CLME. However, treatment with nickel chloride (NiCl2) (100, 300 and 400 μM), a putative Na+-Ca2+ exchanger inhibitor, concentration-dependently reduced the vasorelaxant responses of CLME. Precisely, NiCl2 at 100, 300 and 400 μM significantly (P<0.05) decreased the pD2 and Emax values of CLME (1.86 ± 0.03 and 81.3 ± 1.2%, 1.77 ± 0.03 and 60.2 ± 0.8%, 1.69 ± 0.04 and 55.3 ± 1.6%, respectively). Also, CLME (100 μg/ml) produced less relaxant effect with decreasing extracellular Na+ concentration. CLME-induced vasorelaxation was completely abolished in a Na+-free Tyrode's solution, a condition that eliminates the influence of the forward mode of the exchanger. The results provide indirect evidence that the stimulation of the forward mode of Na+-Ca 2+ exchanger may probably contribute to the vasorelaxation induced by CLME in endothelium-denuded arterial rings.
In clinical and experimental settings, the 13C breath test is performed to measure gastric emptying and has advantages of noninvasiveness and repeatability. We intended to apply the 13C breath test method to mice with an easy-to-handle solid test meal that is more physiological than liquid meals. Male ddY mice were trained to eat 13C-acetate-containing pellets as the solid test meal. Thirty minutes after administration of metoclopramide (0.3-3 mg/kg, p.o.) or atropine sulfate (0.3-3 mg/kg, i.p.), mice received the test meal and were placed in chambers. The 13CO2 levels in the expired air were measured and the maximum concentration (Cmax; ‰) and the time to reach the maximum concentration (Tmax; min) were determined. Metoclopramide significantly and dose-dependently increased Cmax and decreased Tmax. On the other hand, atropine sulfate significantly and dose-dependently decreased Cmax and increased Tmax. The 13C-acetate breath test using a solid test meal is sensitive enough to detect both enhanced and delayed gastric emptying of the reference drugs.
Extracts of Hypoxis hemerocallidea corm (African potato) are commonly used by some traditional health practitioners in KwaZulu-Natal Province of South Africa as natural antenatal remedy to prevent threatening or premature abortion and miscarriage, and to ensure successful confinement. In this study, we investigated the uterolytic activity of H. hemerocallidea corm aqueous extract on spontaneous, rhythmic contractions of uterine horns taken from pregnant rats and guinea-pigs, as well as on spasmogen-provoked contractions of stilboesterol-primed, oestrogen-dominated, non-pregnant rat and guinea-pig isolated uterine horns. Relatively low to high concentrations of H. hemerocallidea corm aqueous extract (APE, 25-400 mg/ml) inhibited the amplitude of the spontaneous, rhythmic contractions of, and relaxed, uterine horns isolated from pregnant rats and guinea-pigs in a concentration-related manner. Furthermore, relatively low to high concentrations of APE (25-400 mg/ml) relaxed basal tones of uterine horns taken from non-pregnant, oestrogen-dominated rats and guinea-pigs in a concentration-dependent manner. The same moderately low to high concentrations of APE (25-400 mg/ml) inhibited acetylcholine-, oxytocin-, bradykinin-, and potassium chloride (K+)-induced contractions of oestrogen-dominated rat and guinea-pig isolated uterine horns in a concentration-related manner. Although the mechanism of uterolytic action of APE could not be established, the results of the present study lend pharmacological credence to the folkloric, ethnomedical uses of APE as a natural antenatal remedy for threatening or premature abortion, and suggest that the uterolytic action of the corm's extract is unlikely to be mediated via β2-adrenoceptor stimulation, but probably mediated through a non-specific spasmolytic mechanism.
The primary goal of this study was to investigate the effect of long-term (9 months) streptozotocin (STZ)-induced diabetes on the coronary vasoconstrictor responses to vasoactive agents such as high K+, acetylcholine (ACh), endothelin-1 (ET-1), and the calcium-channel activator Bay K 8644. For this, we used isolated rat hearts perfused at constant flow rate. Each of the four agents caused dose-dependent increases in perfusion pressure in isolated hearts from age-matched control and STZ-induced diabetic rats. The dose-response curves for high K+, ACh, and ET-1 were shifted to the left, so that at some lower doses of these agents the increased perfusion pressure was greater in coronary arteries obtained from diabetic rats than in those from control rats. On the other hand, the maximum contractile response induced by each of these agents was lower in the diabetic perfused heart. The Bay K 8644-induced contractile response was significantly greater in the coronary arteries of diabetic rats than in those of control rats. A threshold-constrictor concentration of Bay K 8644 (1 nM) potentiated the ACh-induced vasoconstriction in coronary arteries from both groups, and the potentiated responses were greater in diabetic rats than in controls at lower concentrations of ACh (100 nM and 1 μM). These findings suggest that the coronary artery contractile responses to lower concentrations of ACh or ET-1 are exaggerated in long-term STZ-induced diabetic hearts. These changes may be due to alterations in the activity of voltage-gated Ca2+ channels.