Segmental heterogeneity in the mechanism of sodium nitroprusside-induced relaxation in ovine pulmonary artery

K. Sathishkumar, R. Gracious Ross, Dnyaneshwar U. Bawankule, Kautuk K. Sardar, Vellanki Ravi Prakash, Santosh K. Mishra

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)491-498
Number of pages8
JournalJournal of cardiovascular pharmacology
Volume45
Issue number6
DOIs
StatePublished - Jun 2005

Keywords

  • CGMP
  • K-ATPase
  • Na
  • Pulmonary artery
  • Sodium nitroprusside
  • Vasodilation
  • Voltage-gated potassium channel

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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