Vasorelaxation of rat thoracic aorta caused by two Ca(2+)-channel blockers, HA-22 and HA-23.
The pharmacological effects of HA-22 (2-(4'methoxyphenylmethyl)-3,4-dimethylpyrano[2,3-c]pyrazol- 6(2H)-one) and HA-23 (2-(2'-thienylmethyl)-3,4-dimethylpyrano[2,3-c]pyrazol-6(2H) -one) on rat isolated thoracic aorta have been examined. In high potassium medium (60 mM), Ca2+ (0.03-3 mM)-induced vasoconstriction was inhibited by HA-22 and HA-23 (10-100 micrograms mL-1). Cromakalim-relaxed aortic rings precontracted with 15 mM but not 60 mM K+. However, HA-22, HA-23 and verapamil produced a greater relaxation in 60 mM than in 15 mM K(+)-induced contraction. The tonic contractions elicited by KCl (60 mM) and Bay K 8644 (10(-7)M) were also relaxed by the addition of HA-22 and HA-23. The phenylephrine concentration-response curves displayed antagonism by HA-22 and HA-23 (10-100 micrograms mL-1) in a non-competitive manner. The caffeine (10 mM)-induced contraction and cAMP or cGMP levels were not affected by HA-22 or HA-23. It is concluded that HA-22 and HA-23 relaxed the rat aorta by suppressing the Ca2+ influx through both voltage-dependent and receptor-operated Ca2+ channels.
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
S M
SM
Yu
S C
SC
Kuo
L J
LJ
Huang
S S
SS
Sun
T F
TF
Huang
C M
CM
Teng
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001578:Benzopyrans / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D019806:Cromakalim; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011714:Pyrans / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology; D047630:Depsipeptides
D001578:Benzopyrans; D002110:Caffeine; D002121:Calcium Channel Blockers; D019806:Cromakalim; D000242:Cyclic AMP; D006152:Cyclic GMP; D009543:Nifedipine; D011714:Pyrans; D011720:Pyrazoles; D011758:Pyrroles; D014700:Verapamil; C077810:HA 22; C077811:HA 23; D047630:Depsipeptides