Pharmacological evidence for calcium channel inhibition by danshen (Salvia miltiorrhiza) on rat isolated femoral artery.
This study investigated the relaxant actions of danshen (Salvia miltiorrhiza) and its lipid-soluble- and water-soluble-fractions on endothelium-denuded rat isolated femoral artery rings. Danshen, its water-soluble fraction and its lipid-soluble fraction produced relaxation of the phenylephrine-precontracted artery rings with IC50 values of 149 +/- 20 microg/mL, 160 +/- 25 microg/mL, and 23 +/- 6 microg/mL, respectively. Pretreatment of the artery rings with a non-selective potassium channel inhibitor tetraethylammonium (TEA, 10 mM) produced a significant two-fold rightward shift of the concentration-response curve to danshen and a four-fold shift to its water-soluble fraction, but had no effect on the lipid-soluble fraction. A 3.3-fold shift was produced on the concentration-response curve of danshen when the artery rings were pretreated with a mixture of 10 mM TEA, 1 mM 4-aminopyridine (K(V) blocker), 1 microM glibenclamide (K(ATP) blocker), 100 nM iberiotoxin (BK(Ca) blocker), and 100 microM barium chloride (K(IR) blocker). Involvement of Ca2+ channels was investigated in endothelium-denuded artery rings incubated with Ca2+-free buffer and primed with 1 microM phenylephrine or 60 mM KCl for 5 minutes prior to adding CaCl2 to elicit contraction. In artery rings primed with phenylephrine, pretreatment with 1 mg/mL danshen, 1 mg/mL water-soluble fraction of danshen, 0.1 mg/mL lipid-soluble fraction of danshen, and 100 nM nifedipine abrogated the CaCl2-induced contraction. On the other hand, in artery rings primed with KCl, these agents produced 40%, 25%, 53%, and 92% inhibition on the maximum contraction induced by CaCl2, respectively. Increasing the concentrations of danshen and its water-soluble fraction to 3 mg/mL, and the lipid-soluble fraction to 0.3 mg/mL further reduced the maximum contraction to 92%, 93%, and 83%, respectively. Taken together, these findings suggested the vasorelaxant actions of danshen and its fractions were produced primarily by inhibition of Ca2+ influx in the vascular smooth muscle cells and a small component was mediated by the opening of K+ channels.
Lam
Francis Fu Yuen
FF
From the Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Yeung
John Hok Keung
JH
Cheung
Jessica Ho Yan
JH
Or
Penelope Mei Yu
PM
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D002121:Calcium Channel Blockers; D010936:Plant Extracts; D026902:Potassium Channel Blockers; D013757:Tetraethylammonium Compounds; D002122:Calcium Chloride