Patchouli Alcohol Isolated from Pogostemon Cablin Mediates Endothelium-Independent Vasorelaxation by Blockade of Ca2+ Channels in Rat Isolated Thoracic Aorta

5 years ago

Patchouli Alcohol Isolated from Pogostemon Cablin Mediates Endothelium-Independent Vasorelaxation by Blockade of Ca2+ Channels in Rat Isolated Thoracic Aorta

The aerial parts of Pogostemon cablin (Blanco) Benth. for the treatment of cardiodynia have been documented in Mingyi Bielu of late Han Dynasty, in addition to that the Ca²⁺ antagonized activities of P. cablin and its critically pharmacological ingredient patchouli alcohol (PA) were reported previously.

Aim of the study

To investigate the relaxant effects of PA on rat isolated thoracic aortas and further explore its potential mechanisms of actions.

Materials and methods

The aortas with endothelium and without endothelium were prepared and suspended in the organ bath for isometric tension recordings. The responses to accumulative concentrations of PA in endothelium-intact (E+) aortas with basal tension and in different treated aortas pre-contracted with potassium chloride (KCl) or phenylephrine (PHE) were observed; the effects of L-NAME and indomethacin in aortas with intact endothelium, and of L-NAME, propranolol, tetraethtylamine (TEA), 4-aminopyridine (4-AP), barium chloride (BaCl2), glyburide in aortas with endothelial denudation on PA-produced vasorelaxation were assessed; the influences of PA on extracellular Ca²⁺ influx and intracellular Ca²⁺ release were measured in Ca²⁺-free medium. Finally, the abilities of PA to inhibit KCl- and PHE-induced contractions were compared to that of verapamil in E- aortas.

Results

PA produced vasorelaxant effects in KCl- and PHE-precontracted E+ aortas in a concentration-dependent manner, which had no statistically different from that in KCl- and PHE-precontracted E- aortas. PA (10μM) significantly reduced KCl-induced contractions while PHE-induced contractions were significantly reduced by 100μM of PA instead of 10μM and 30μM in aortas with endothelium. Pre-incubation of E+ aortas with L-NAME as well as indomethacin and of E- aortas with L-NAME, propranolol, TEA, 4-AP, BaCl2 and glyburide had no obvious effects on vasorelaxation of PA. In endothelium-removed aortas around Ca²⁺-free solution, PA remarkably lowered the contractions stimulated with Ca²⁺ and PHE, and application of ruthenium red and heparin further enhanced the abilities of PA to reduce PHE-caused contractions. In aortas without endothelium, 100μM of PA markedly attenuated KCl-induced contractions but not affect PHE-induced contractions. Verapamil at the equal dose markedly attenuated KCl- and PHE-induced contractions, and the inhibitory effects on KCl-induced contractions were more forceful than that on PHE-induced contractions. In combined usage, the inhibitory effects on the contractions elicited by KCl were evidently weaker than that of verapamil alone and indifferently stronger than that of PA alone, and the inhibitory effects on the contractions elicited by PHE were evidently weaker than that of single verapamil but stronger than that of single PA.

Conclusion

PA may act as a Ca²⁺ antagonist to exert an intensively vasorelaxant effects through endothelium-independent pathway, and its mechanisms underlying the vasoactivities seem to be associated with the blockade of extracellular Ca²⁺ influx through VDCCs and ROCCs in vascular smooth muscle cells (VSMCs) membrane and intracellular Ca²⁺ releases through IP3R- and RYR-mediated Ca²⁺ channels in sarcolemma.

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DOI: S037887411731379X