ABSTRACT
OBJECTIVE: There are some reports on hypotensive and antispasmodic effects of Teucrium polium L. (Lamiaceae) (TP). SUBJECTS AND METHODS: The activity of different concentrations of TP extract (1, 2, 4 and 8 mg/ml) was evaluated on contractile responses of isolated aorta to potassium chloride (KCl) and phenylephrine (PE). RESULTS: The cumulative concentrations of the extract induced a concentration-dependent relaxation in the aorta precontracted by PE and KCl. Extract-induced vasorelaxations in denuded aortic rings precontracted by PE and KCl at lower concentrations were considerably less than intact aortic rings, but this effect was significantly more at concentrations of 4 mg/ml for PE-, 4 and 8 mg/ml for KCl-induced contractions. All the extract concentrations (except 1 mg/ml) significantly relaxed PE-induced contraction in the presence of NG-nitro-L-arginine methyl ester. Indomethacin reduced effectively extract-induced vasorelaxation at 1 and 2 mg/ml. The extract reduced PE- and KCl-induced contractions in the presence of cumulative calcium concentrations and after incubation with diltiazem; this vasorelaxant effect of TP was decreased. TP-induced relaxation was inhibited by heparin, ruthenium red, glibenclamide, and tetraethylammonium, but 4-aminopyridine had no effect on TP-induced relaxation. CONCLUSION: TP extract has vasorelaxant effect on isolated rat thoracic aorta which mediated by endothelium-dependent and endothelium-independent mechanisms. The relaxation mainly was mediated by inhibition of calcium influx in vascular smooth muscle cells. It seems that the vasorelaxant effect of extract at lower concentrations was mediated by nitric oxide and prostacyclin. SUMMARY: The vasodilatory effect of Teucrium polium L. was mediated by several mechanisms. First: Teucrium polium L. inhibited receptor operated ROCC and VDCC. Second: Teucrium polium L. also inhibited KATP and KCa channels. Third: Teucrium polium L. blocked IP3 receptor and reduced the release of calcium from intracellular source. Forth: Teucrium polium L. increased the release on NO and PGI2 from endothelial cells. Abbreviations Used: ROCC: Receptor operated calcium channels, VDCC: Voltage dependent calcium channels, PLC: Phospholipase C, IP3: 1,4,5 triphosphate inositol, IP3R: IP3 receptors, SR: sarcoplasmic reticulum, RYR: ryanodine receptors, K+ATP: ATP-sensitive potassium channel, K+Ca: Calcium-activated potassium channel, cAMP: Cyclic adenosine monophosphate, cGMP: Cyclic guanosine monophosphate, PGI2: Prostaglandin I2, NO: Nitric oxide.
ABSTRACT
OBJECTIVE: The aim of this study was to elucidate the mechanism(s) responsible for the vasorelaxant effect of Nigella sativa (N. sativa). METHODS: The activity of different concentrations of N. sativa extract was evaluated on contractile responses of isolated aorta to KCl and phenylephrine (PE). RESULTS: The extract (2-14 mg/mL) induced a concentration dependent relaxation both in endothelium-intact and endothelium-denuded aortic rings precontracted by PE (10(-6) M) and KCl (6 × 10(-2) M). Extract reduced PE- and KCl-induced contractions in presence of cumulative concentrations of calcium (10(-5)-10(-2) M) significantly. L-NAME and indomethacin had no effect on vasorelaxation effect of extract in PE-induced contraction. Diltiazem and heparin reduced significantly this vasorelaxation at a concentration of 14 mg/mL of extract; however, N. sativa-induced relaxation was not affected by ruthenium red. Tetraethylammonium chloride reduced the extract-induced relaxation in concentrations of 2-6 mg/mL of extract significantly but glibenclamide reduced this relaxative effect in all concentrations of extract. CONCLUSIONS: The inhibitory effect of N. sativa seed extract on the contraction induced by PE and KCl was endothelium-independent. This relaxation was mediated mainly through the inhibition of Ca(2+) and KATP channels and also intracellular calcium release.
Subject(s)
Aorta/drug effects , Calcium Channels/metabolism , Endothelium, Vascular/drug effects , Nigella sativa/chemistry , Plant Extracts/pharmacology , Potassium Channels/metabolism , Seeds/chemistry , Vasodilation/drug effects , Animals , Aorta/metabolism , Calcium/metabolism , Endothelium, Vascular/metabolism , Muscle Contraction/drug effects , NG-Nitroarginine Methyl Ester/metabolism , Plant Extracts/chemistry , Rats , Rats, Wistar , Vasodilator Agents/pharmacokineticsABSTRACT
BACKGROUND: Achillea wilhelmsii (A. wilhelmsii) is used in Iraninan folk medicine for the treatment of hypertension; also, in previous reports, the hypotensive and antihypertensive effects of this plant have been indicated. The aim of the present study is to investigate the vasorelaxant effect of the hydroalcholic extract of A. wilhelmsii and its underlying mechanisms in isolated rat aorta. MATERIALS AND METHODS: The effect of the hydroalcholic A. wilhelmsii extract was tested on the contractile response of Wistar rat aorta induced by potassium chloride (KCl) and phenylephrine (PE) using a pressure transducer that is connected to the PowerLab. RESULTS: The cumulative concentrations of A. wilhelmsii (0.5-8 mg/ml) induced a vasorelaxation both in endothelium-intact and endothelium-denuded aortas precontracted by high K(+) (6 × 10(-2) M) or 10(-6) M PE. A. wilhelmsii, at a concentration of 4 mg/ml, reduced Ca(2+)-induced contraction (P < 0.001 vs. control) after PE or KCl had generated a stable contraction in the Ca(2+)-free solution. Furthermore, after incubation with diltiazem, the vasorelaxant effect of A. wilhelmsii reduced in the endothelium-denuded aortas precontracted by PE or KCl (P < 0.001 vs. control). In contrast, A. wilhelmsii-induced relaxation was not affected by glibenclamide, BaCl2, ruthenium red, methylene blue, or heparin. CONCLUSIONS: The results showed that A. wilhelmsii had a vasorelaxation effect, which was not endothelium-dependent. The relaxation was mediated by inhibition of extracellular Ca(2+) influx through voltage- and receptor-operated Ca(2+) channels (VDDCs and ROCCs) in vascular smooth muscle cells.
