Vol. 297, Issue 1, 181-188, April 2001

Natriuretic Peptide-Induced Relaxation of Myometrium from the Pregnant Guinea Pig Is Not Mediated by Guanylate Cyclase Activation

Jorge A. Carvajal, Kripamoy Aguan, Loren P. Thompson, Irina A. Buhimschi and Carl P. Weiner

Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland Baltimore, School of Medicine, Baltimore, Maryland

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 10⁸ M oxytocin, and relaxation to the cumulative addition (10⁹-10⁶ 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 (10⁷ M) was significantly less than that produced by ANP (10⁷ 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.