Nitric oxide and sodium nitroprusside-induced relaxation of the human umbilical artery

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Abstract

1 In the human umbilical artery (HUA) pre-contracted with the thromboxane mimetic U46619 or with 5-hydroxytryptamine (5-HT), (and pretreated with indomethacin (3 μM) to suppress the synthesis of prostanoids), authentic nitric oxide (NO) evoked concentration-dependent relaxation (pEC 50 7.05 and 5.99, respectively). In contrast, sodium nitroprusside (SNP) induced relaxation only in U46619 pre-contracted HUA (pEC 50 6.52). 2 At high (>300 mmHg) vs low (<55 mmHg) oxygen tension the dose-response curves to NO- and SNP-induced relaxations were biphasic and shifted leftward. 3 Preincubation of the arterial rings with the soluble guanylyl cyclase (sGC) inhibitor 1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μM) shifted the concentration-response curve to NO, reduced the maximal relaxation response to NO (E(max) 71%) and to SNP (E(max) 10%). 4 Pre-exposure of HUA rings to high extracellular K + (50 mM) reduced E(max) relaxation responses to NO (36%) and SNP (1%). 5 Pretreatment of the HUA with the K + channel inhibitors, tetraethylammonium (TEA, 1 mM), 4-aminopyridine (4-AP, 0.5 mM), charybdotoxin (0.1 μM) or iberiotoxin (0.1 μM) increased the pEC 30 for NO and SNP and changed the shape of the dose-response curves from biphasic to monophasic. 6 Pre-incubation of HUA rings with TEA (1 mM), 4-AP (0.5 mM) and ODQ (10 μM) significantly reduced the NO-induced maximal relaxation (E(max) 26%) but not the pEC 50 (5.60). 7 These data indicate that SNP-induced relaxation in the HUA is primarily mediated via sGC-cyclic GMP whereas NO-induced relaxation also involves the activation of K(V) and K(Ca) channels and a cyclic GMP/K + channel-independent mechanism(s).

Original languageEnglish
Pages (from-to)521-529
Number of pages9
JournalBritish Journal of Pharmacology
Volume131
Issue number3
Publication statusPublished - 2000
Externally publishedYes

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Keywords

  • Guanylyl cyclase
  • Human umbilical artery
  • Nitric oxide
  • Potassium channels
  • Sodium nitroprusside

ASJC Scopus subject areas

  • Pharmacology

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