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

In the human umbilical artery (HUA) pre‐contracted with the thromboxane mimetic U46619 or with 5‐hydroxytryptamine (5‐HT), (and pretreated with indomethacin (3 μ 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 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 μ M ) 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 m M ) reduced E max relaxation responses to NO (36%) and SNP (1%). Pretreatment of the HUA with the K + channel inhibitors, tetraethylammonium (TEA, 1 m M ), 4‐aminopyridine (4‐AP, 0.5 m M ), charybdotoxin (0.1 μ M ) or iberiotoxin (0.1 μ M ) 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 m M ), 4‐AP (0.5 m M ) and ODQ (10 μ M ) 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).British Journal of Pharmacology (2000) 131 , 521–529; doi: 10.1038/sj.bjp.0703588