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

1 In the human umbilical artery (HUA) pre-contracted with the thromboxane mimetic U46619 or with 5-hydroxytryptamine (5-HT), land pretreated with indomethacin (3 mu M) 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 pie-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 mu M) 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 Ki channel inhibitors, tetraethylammonium (TEA, 1 mM), 4-aminopyridine (4-AP, 0.5 mM), charybdotoxin (0.1 mu M) or iberiotoxin (0.1 mu M) increased the PEC30 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 mu M) 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 KCa channels and a cyclic GMP/K+ channel-independent mechanism(s).