Carvajal J A, Aguan K, Thompson L P, Buhimschi I A, Weiner C P
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Bressler Research Building, 655 W. Baltimore St., Baltimore, MD 21201, USA.
J Pharmacol Exp Ther. 2001 Apr;297(1):181-8.
We tested both relaxation and cGMP generation by atrial (ANP), brain (BNP), and C-type natriuretic peptide (CNP) in oxytocin-stimulated myometrium from near-term pregnant guinea pigs to investigate the ability and mechanism of natriuretic peptides to inhibit myometrial contractility. Myometrial strips were contracted by 10(-8) M oxytocin, and relaxation to the cumulative addition (10(-9)-10(-6) M) of the natriuretic peptides measured. Maximal relaxation to BNP was significantly greater than to ANP (52 versus 32% respectively; p < 0.05), whereas CNP failed to produce relaxation. However, the increase in cGMP produced by BNP (10(-7) M) was significantly less than that produced by ANP (10(-7) M) (4.5 versus 7.0 times basal; p < 0.05); CNP did not increase myometrial cGMP. Anantin, a competitive blocker of the guanylate cyclase A receptor, significantly reduced the increase in cGMP produced by ANP and BNP, but had no effect on relaxation induced by either peptide. Rp-8-Br-cGMP, an inhibitor of the cGMP-dependent protein kinase, did not alter BNP-induced relaxation. The atrial natriuretic peptide-fragment 4-23 amide, a natriuretic peptide clearance receptor agonist, failed to inhibit oxytocin-stimulated myometrial contraction. We conclude that natriuretic peptide induced relaxation of oxytocin-stimulated myometrium from the pregnant guinea pig is not mediated by either guanylate cyclase A or B activation, is independent of the cGMP pathway, and does not involve clearance receptor activation. Our results suggest that natriuretic peptide-induced relaxation of pregnant myometrium is mediated via a novel mechanism.
我们检测了心房钠尿肽（ANP）、脑钠尿肽（BNP）和C型钠尿肽（CNP）在近足月妊娠豚鼠子宫肌层中催产素刺激下的舒张作用和环磷酸鸟苷（cGMP）生成情况，以研究钠尿肽抑制子宫肌层收缩的能力和机制。子宫肌条用10⁻⁸ M催产素收缩，然后测量对钠尿肽累积添加量（10⁻⁹ - 10⁻⁶ M）的舒张反应。BNP引起的最大舒张显著大于ANP（分别为52%和32%；p < 0.05），而CNP未能产生舒张作用。然而，BNP（10⁻⁷ M）引起的cGMP增加显著低于ANP（10⁻⁷ M）（分别为基础值的4.5倍和7.0倍；p < 0.05）；CNP未增加子宫肌层cGMP。鸟苷酸环化酶A受体的竞争性阻断剂阿那替丁显著降低了ANP和BNP引起的cGMP增加，但对两种肽诱导的舒张无影响。cGMP依赖性蛋白激酶抑制剂Rp - 8 - Br - cGMP未改变BNP诱导的舒张。钠尿肽清除受体激动剂心房钠尿肽片段4 - 23酰胺未能抑制催产素刺激的子宫肌层收缩。我们得出结论，钠尿肽诱导的妊娠豚鼠子宫肌层催产素刺激舒张不是由鸟苷酸环化酶A或B激活介导的，独立于cGMP途径，且不涉及清除受体激活。我们的结果表明，钠尿肽诱导的妊娠子宫肌层舒张是通过一种新机制介导的。
