Al. Cogolludo et al., Mechanisms involved in SNP-induced relaxation and [Ca2+](i) reduction in piglet pulmonary and systemic arteries, BR J PHARM, 132(4), 2001, pp. 959-967
I We have compared the mechanisms involved in sodium nitroprusside (SNP)-in
duced relaxation and [Ca2+](i) reduction in isolated piglet pulmonary (PA)
and mesenteric (MA) arteries.
2 SNP (10(-x) M - 3 x 10(-5) M) evoked a concentration-dependent relaxation
of PA and MA (pD(2)=6.66+/-0.06 and 6.74+/-0.14, respectively) stimulated
by noradrenaline, which was markedly reduced by the guanylate cyclase inhib
itor ODQ. In fura 2-incubated PA and MA, SNP produced a parallel reduction
in contractile force and in [Ca2+](i), expressed as the ratio of emitted fl
uorescence at 340 and 380 nm (F340/F380).
3 The inhibition of the Na+/K+-ATPase after the incubation in a K+-free med
ium or the exposure to ouabain (10(-6) M) inhibited SNP-induced relaxation
in MA but not in PA. SNP-induced relaxation was not attenuated by 80 mM KCl
plus nifedipine (10(-6) M) but was inhibited by thapsigargin (2 x 10 (-6)
M; pD(2) = 5.69+/-0.19 and 5.89+/-0.19 for PA and MA, respectively).
4 Pretreatment of PA with thapsigargin and MA with thapsigargin plus ouabai
n induced a stronger inhibition on the reduction in [Ca2+](i) than on the r
elaxation induced by SNP, indicating the existence of Ca2+-independent mech
anisms.
5 The activation of the Na+/K+-ATPase by the addition of KCI after the incu
bation in a K+-free medium similarly reduced [Ca2+](i) in PA and MA, wherea
s it relaxed with much less efficacy PA than MA. 6 We conclude that SNP red
uces [Ca2+]i and causes relaxation through the activation of SERCA in PA an
d SERCA and Na+/K+-ATPase in MA. However, Ca2+-independent mechanisms also
contribute to SNP-induced effects.