Preeclampsia (PE) is a pregnancy-specific syndrome attributable to endothelial dysfunction. This dysfunction has been induced in isolated human myometrial arteries by plasma obtained from women with PE, pre- and post-diagnosis (Hayman et al. 2000, Myers et al. 2003). Characterisation of vasoactive factors within such plasma promises to increase our understanding of the pathophysiology of PE. We have studied human myometrial vessels by small vessel wire myography, but patient and vessel variability is marked and sample availability limited. Mouse mesenteric vessels may represent a more appropriate stringent model to characterise these plasma factors.
Ethical approval was obtained for experiments on human tissue. With written informed consent myometrial samples were taken at Caesarean section from women (n = 10) with uncomplicated pregnancies at term. Male C57B mice (n = 8) were humanely killed by stunning, followed by cervical dislocation. Myometrial or mesenteric vessels were mounted on a wire myograph and normalised in physiological salt solution (95 % air-5 % CO2; 37 °C). Arteries were constricted to incremental doses of arginine vasopressin (AVP) (10-10-10-8 M), U46619 (10-10-10-6 M) or phenylephrine (Phe) (10-9-10-5 M), and exposed to the endothelial-dependent vasodilators bradykinin (BK) (10-10-10-6 M) or acetylcholine (ACh) (10-9-10-5 M). Mechanisms of endothelial-dependent relaxation were elucidated by prostacyclin and NO blockade with indomethacin (10 µM) and N-nitro-L-arginine (LNNA; 100 µM), respectively.
Mouse mesenteric and human myometrial vessels constricted to all agonists. In mouse mesenteric arteries, contractile responses to AVP were oscillatory but sustained to Phe or U46619. In contrast, sustained constrictions were produced by human myometrial vessels in response to AVP and U46619, but not to Phe. Mesenteric vessels relaxed in a dose-dependent manner to ACh, but not to BK, whereas myometrial vessels relaxed to BK, but not to ACh. Coincubation with indomethacin and LNNA, attenuated maximal ACh-induced relaxation vs.control vessels (maximal relaxation 56.2 ± 9.61 % vs. 23.1 ± 4.3% means ± S.E.M.; Student’s unpaired t test, P ²le³ 0.05). The ACh-dependent NO/prostacyclin-independent relaxation of mouse mesenteric vessels was similar to the BK-dependent NO/prostacyclin-independent relaxation of human myometrial vessels (maximal relaxation 55.4 ± 12.6 % vs. 14.1 ± 5.4% P ²le³ 0.05).
Thus, mouse mesenteric and human myometrial vessels differed in agonist-mediated endothelial-dependent relaxations. However, the NO/prostacyclin-independent component of agonist-induced vasodilatation, attributable to EDHF, was similar in both vascular beds.
This work was supported by Tommys, the baby charity