TY - JOUR
T1 - Segmental heterogeneity in the mechanism of sodium nitroprusside-induced relaxation in ovine pulmonary artery
AU - Sathishkumar, K.
AU - Ross, R. Gracious
AU - Bawankule, Dnyaneshwar U.
AU - Sardar, Kautuk K.
AU - Prakash, Vellanki Ravi
AU - Mishra, Santosh K.
PY - 2005/6
Y1 - 2005/6
N2 - Segmental heterogeneity in relaxation response to nitric oxide (NO) was examined using NO donor sodium nitroprusside (SNP) in second- (medium) and fourth-generation (small) ovine isolated intralobar pulmonary arteries. In vessels precontracted with serotonin, NO donors SNP and S-nitroso-N- acetylpenicillamine (SNAP) were more potent in relaxing medium, in comparison to the small, arteries. Soluble guanylyl cyclase (sGC) inhibitor [1,2,4]oxadiazolo-[4,3-a]quinoxaline-1-one (ODQ 3 μM) caused a profound inhibition of SNP relaxation in small as compared with medium-sized arteries. However, both basal and SNP (10 μM)-stimulated intracellular cyclic guanosine monophosphate (cGMP) content was identical in these 2 arterial segments. The Na+,K+-ATPase inhibitor ouabain (1 μM) had a marked inhibitory effect on SNP-mediated relaxation in both segments. There was no segmental difference in SNP (10 μM)-stimulated plasma membrane Na +,K+-ATPase activity and ouabain-sensitive 86Rb-uptake. 4-AP (1 mM), a relatively selective inhibitor of K v channels, decreased the potency of SNP relaxation by about 10-fold in the medium-sized vessels. On the other hand, 4-AP was without effect on the vasodilator potency of SNP in small vessels. Interestingly, in the presence of 4-AP, SNP was equipotent in dilating both medium (pD2 = 5.80 ± 0.07; Emax = 84 ± 1.6%, n = 7) and small (pD2 = 5.74 ± 0.15; Emax = 83 ± 2.5%, n = 7) pulmonary arteries. In conclusion, the results of the present study suggest that K v channels determine the segmental heterogeneity of NO-mediated relaxation in ovine pulmonary artery.
AB - Segmental heterogeneity in relaxation response to nitric oxide (NO) was examined using NO donor sodium nitroprusside (SNP) in second- (medium) and fourth-generation (small) ovine isolated intralobar pulmonary arteries. In vessels precontracted with serotonin, NO donors SNP and S-nitroso-N- acetylpenicillamine (SNAP) were more potent in relaxing medium, in comparison to the small, arteries. Soluble guanylyl cyclase (sGC) inhibitor [1,2,4]oxadiazolo-[4,3-a]quinoxaline-1-one (ODQ 3 μM) caused a profound inhibition of SNP relaxation in small as compared with medium-sized arteries. However, both basal and SNP (10 μM)-stimulated intracellular cyclic guanosine monophosphate (cGMP) content was identical in these 2 arterial segments. The Na+,K+-ATPase inhibitor ouabain (1 μM) had a marked inhibitory effect on SNP-mediated relaxation in both segments. There was no segmental difference in SNP (10 μM)-stimulated plasma membrane Na +,K+-ATPase activity and ouabain-sensitive 86Rb-uptake. 4-AP (1 mM), a relatively selective inhibitor of K v channels, decreased the potency of SNP relaxation by about 10-fold in the medium-sized vessels. On the other hand, 4-AP was without effect on the vasodilator potency of SNP in small vessels. Interestingly, in the presence of 4-AP, SNP was equipotent in dilating both medium (pD2 = 5.80 ± 0.07; Emax = 84 ± 1.6%, n = 7) and small (pD2 = 5.74 ± 0.15; Emax = 83 ± 2.5%, n = 7) pulmonary arteries. In conclusion, the results of the present study suggest that K v channels determine the segmental heterogeneity of NO-mediated relaxation in ovine pulmonary artery.
KW - CGMP
KW - K-ATPase
KW - Na
KW - Pulmonary artery
KW - Sodium nitroprusside
KW - Vasodilation
KW - Voltage-gated potassium channel
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U2 - 10.1097/01.fjc.0000159043.50488.ac
DO - 10.1097/01.fjc.0000159043.50488.ac
M3 - Article
C2 - 15897774
AN - SCOPUS:19544389164
SN - 0160-2446
VL - 45
SP - 491
EP - 498
JO - Journal of cardiovascular pharmacology
JF - Journal of cardiovascular pharmacology
IS - 6
ER -