Non-guanylate cyclase-mediated relaxations to NO in the human umbilical artery (HUA)
In superfusion studies the HUA has been shown to release an EDRF in response to histamine, bradykinin, ATP and the Ca2+ ionophore A23187 but responds comparatively weakly to acetylcholine. Also, it has been found that elevated cyclic nucleotide levels in HUA are not associated with mechanical relaxation when SNP was used as the NO donor in tissues precontracted with 5-HT. In the present study we have evaluated the influence of contractile agonists on SNP and NO inducedrelaxation in HUA. Rings of the HUA were contracted with thromboxane A2 mimetic U44069(U), histamine or 5-HT, and the effects of SNP and NO investigated. In U-contracted tissues SNP and NO caused concentration dependent relaxations with pD2s 6.69 ±0.21 and Rmax 90 ±8; and 6.0 ±0.5 and Rmax 85 ± 10, respectively, whereas for histamine the pD2 values were 5.47 ± 0.36 and Rmax 80 ±7 and pD2 6.2 ±0.9 and Rmax 94 ±6. When tone in the HUA was induced with 5-HT, SNP failed to relax the tissue while for NO the pD2 was 5.6 ±0.2 and Rmax 76 1 12. KC1-contracted tissues failed to relax to either SNP or NO. Neither exposure to 10 |uM méthylène blue nor LY 83583 (putative guanylate cyclase inhibitors) for 30 min significantly inhibited relaxations to SNP or NO. This study has shown that: (i) The relaxation response of the HUA is dependent upon the agonist used to initiate contraction.; (ii) SNP- and NO-mediated relaxations of the HUA may not be dependent on guanylate cyclase activation; and (iii) The relaxation responses to SNP and NO may involve hyperpolarization of the HUA.