Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels.

German chamomile (Matricaria recutita L.), a widely-used herbal medicine, has been reported to have a wide range of biological effects, including smooth muscle relaxation. The aim of this study was to compare the effects of representative compounds from chamomile (apigenin, luteolin, (-)-α-bisabolol, farnesene, umbelliferone; 3-30 µM) on vascular tone using porcine coronary and splenic arteries mounted for isometric tension recording in isolated tissue baths and precontracted with the thromboxane-mimetic U46619. Apigenin, luteolin, and (-)-α-bisabolol produced slow, concentration-dependent relaxations in both the coronary and splenic arteries that were not blocked by inhibition of nitric oxide synthase or potassium channels. Removal of extracellular calcium inhibited the relaxations to all three compounds, and these compounds also inhibited calcium re-addition-evoked contractions, indicating that the relaxation response may be mediated through inhibition of calcium influx. Apigenin and luteolin, but not (-)-α-bisabolol, enhanced the relaxation to the nitric oxide donor sodium nitroprusside, indicating that apigenin and luteolin may act to regulate cyclic GMP levels. Umbelliferone produced a rapid, transient relaxation in the splenic artery, but not the coronary artery, that was inhibited by L-NAME and removal of the endothelium, suggesting an influence on nitric oxide production. Farnesene, at concentrations up to 30 µM, was without effect in either blood vessel. In conclusion, hydroxylated compounds (apigenin, luteolin and (-)-α-bisabolol) found in chamomile all caused a slow relaxation of isolated blood vessels through an effect on calcium influx. Umbelliferone, on the other hand, produced a rapid, transient relaxation dependent upon release of nitric oxide from the endothelium.

Hydrogen sulphide-induced relaxation of porcine peripheral bronchioles.

BACKGROUND AND PURPOSE: Hydrogen sulphide (H2S) is an endogenous gasotransmitter. Although it has been shown to elicit responses in vascular and other smooth muscle preparations, a role for endogenously produced H2S in mediating airway tone has yet to be demonstrated. Therefore, the aim of this study was to determine whether H2S is produced within the airways and to determine the functional effect on airway tone. EXPERIMENTAL APPROACH: Small peripheral airways (<5 mm in diameter) from porcine lungs were set up in isolated tissue baths, pre-contracted with the muscarinic agonist carbachol, and then exposed to either the H2S donor sodium hydrosulphide (NaHS), or the precursor L-cysteine. H2S production from L-cysteine or 3-mercaptopyruvate in tissue homogenates was measured by the methylene blue assay. Expression of the H2S-synthesizing enzymes cystathionine ß-synthase (CBS), cystathionine γ lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (3-MST) were measured by Western blotting. KEY RESULTS: NaHS caused a large relaxation of the airways, which was inhibited partially by pre-contraction with KCl or exposure to tetraethylammonium, but not glibenclamide, paxilline or 4-aminopyridine. L-cysteine also caused a relaxation of the airways which was inhibited by the CBS inhibitor aminooxyacetic acid. Tissue homogenates from airways exposed to L-cysteine or 3-mercaptopyruvate in vitro showed a significant production of H2S. Western blotting demonstrated immunoreactivity to CBS, CSE and 3-MST enzymes in the airways. CONCLUSIONS AND IMPLICATIONS: These data demonstrate that H2S can be produced endogenously within porcine airways causing relaxation. The mechanism of relaxation depends, in part, on K(+) channel activity.