Nitric oxide and sodium nitroprusside-induced relaxation of the human umbilical artery. Academic Article uri icon

Overview

abstract

  • In the human umbilical artery (HUA) pre-contracted with the thromboxane mimetic U46619 or with 5-hydroxytryptamine (5-HT), (and pretreated with indomethacin (3 microM) 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). 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. 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 microM) shifted the concentration-response curve to NO, reduced the maximal relaxation response to NO (E(max) 71%) and to SNP (E(max) 10%). Pre-exposure of HUA rings to high extracellular K(+) (50 mM) reduced E(max) relaxation responses to NO (36%) and SNP (1%). Pretreatment of the HUA with the K(+) channel inhibitors, tetraethylammonium (TEA, 1 mM), 4-aminopyridine (4-AP, 0.5 mM), charybdotoxin (0.1 microM) or iberiotoxin (0.1 microM) increased the pEC(30) for NO and SNP and changed the shape of the dose-response curves from biphasic to monophasic. Pre-incubation of HUA rings with TEA (1 mM), 4-AP (0.5 mM) and ODQ (10 microM) significantly reduced the NO-induced maximal relaxation (E(max) 26%) but not the pEC(50) (5.60). 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).

publication date

  • October 1, 2000

Research

keywords

  • Nitric Oxide
  • Nitroprusside
  • Umbilical Arteries
  • Vasodilation

Identity

PubMed Central ID

  • PMC1572347

PubMed ID

  • 11015303

Additional Document Info

volume

  • 131

issue

  • 3