[Vasorelaxant effect of sulfur dioxide derivatives on isolated aortic rings of rats and its mechanisms].
OBJECTIVE
To investigate the vasorelaxant effect of sulfur dioxide (SO(2)) on isolated aortic rings of rats in vitro and its relaxation mechanisms.


METHODS
We perffused the isolated aortic rings of rats, and precontracted the rings with noradrenaline (NE), then observed the relaxant reactivity of SO(2) derivatives, mixture of sulfite and hydrogen sulfite [Na(2)SO(3)/NaHSO(3) 3:1(amount of substance)], to the aortic rings. Meanwhile, we studied the influence of glibenclamide and nicardipine, blockers of K(ATP) and L-calcium channels, on the vasorelaxant reactivity of SO(2) derivatives. We further incubated the aortic rings with hydroxamate (HDX), the inhibitor of SO(2) endogenous generating enzymes, and SO(2) derivatives (4 mmol/L) in vitro, then observed the contraction of the aortic rings to NE.


RESULTS
Isolated aortic rings of rats exhibited relaxant reactivity to Na(2)SO(3)/NaHSO(3) (0-12 mmol/L) in a concentration-dependent manner. IC(50) of the relaxation curve was (7.28+/-0.12) mmol/Lìand Emax was 78.79%+/-3.24%. Glibenclamide (1x10(-6) mol/L) inhibited the vasorelaxation to low dose Na(2)SO(3)/NaHSO(3) (<or=4 mmol/L), whereas it failed to inhibit the vasorelaxation to high dose of Na(2)SO(3)/NaHSO(3) (>6 mmol/L). Nicardipine (1x10(-9) mol/L) could decrease the contraction of the rings to NE, and even could inhibit the relaxation of Na(2)SO(3)/NaHSO(3) almost completely. The inhibition of the endogenous SO(2) production with HDX (1x10(-4) mol/L), resulted in an increase in the contraction of rings. The contraction curve to NE shifted to the left, and IC(50) also changed from (6.48+/-0.84)x10(-7) mol/L to (3.97+/-1.63)x10(-7) mol/L (P<0.01). However, after the incubation of aortic rings with Na(2)SO(3)/NaHSO(3) (4 mmol/L), the contraction curve to NE shifted to the right, and IC(50) changed from (6.48+/-0.84)x10(-7) mol/L to (4.93+/-0.81)x10(-5) mol/L (P<0.01).


CONCLUSIONS
SO(2) could relax vascular smooth muscles, and the mechanism might be associated with calcium channels and K(ATP) channels, suggesting that endogenous SO(2) could modulate the cardiovascular function.
Du
Shu-xu
SX
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Zhang
Chun-yu
CY
Jin
Hong-fang
HF
Du
Jun-bao
JB
Tang
Chao-shu
CS
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013447:Sulfites / Q000494:pharmacology; D013458:Sulfur Dioxide / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D054086:KATP Channels; D026902:Potassium Channel Blockers; D013447:Sulfites; D014665:Vasodilator Agents; D013458:Sulfur Dioxide; D009529:Nicardipine; C042345:hydrogen sulfite; D005905:Glyburide; D009638:Norepinephrine