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Journal of the Society for Gynecologic Investigation, Vol. 12, No. 1, 14-19 (2005)
DOI: 10.1016/j.jsgi.2004.07.005

Parathyroid Hormone-Related Protein-induced Relaxation of Rat Uterine Arteries: Influence of the Endothelium During Gestation

Ferhat Meziani, MD

Bruno Van Overloop, PhD

Francis Schneider, MD

Physicochimie des Interactions Cellulaires et Moleculaires, CNRS UMR 7034, Universite Louis Pasteur; Service de Reanimation Medicale, Hopital de Hautepierre, Hopitaux Umnversitaires de Strasbourg et Faculte de Medecine de Strasbourg, Strasbourg, France

Alexis Gairard, PhD

Pharmacologie et Physicochimie des Interactions Cellulaires et Moleculaires, CNRS UMR 7034, Universite Louis Pasteur, Faculte de Pharmacie, 74 route du Rhin, 67401 Illkirch Cedex, France; gairard(daspinne.u-strasbg.fr

Objective: Parathyroid hormone-related protein (PTHrP) has been reported to relax different vessels. We investigated the influence of both endothelium and gestation on the relaxation of uterine arteries (UA), which supply blood to myometrium and placenta.

Methods: Small uterine and mesenteric arteries (MA) with (E+) and without endothelium (E-)from day 20 pregnant (P) and nonpregnant (NP) rats were mounted in a myograph, precontracted with phenylephrine (PE) in a physiologic salt solution. Relaxations to PTHrP, acetylcholine, andforskolin were peforrned and expressed as a percentage of the PE-induced contraction. Blockade of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) was also studied with Nw,-nitro-L-arginine methyl ester (L-NAME) and with charybdotoxin + apamin, respectively.

Results: Gestation significantly increases maximal vasodilating effect of acetylcholine in UA (68% vs 52%, P < .05) and sensitivity to acetylcholine in small mesenteric vessels (P < .05). PTHrP relaxes uterine (maximal relaxation P: 32%, NP: 460%), as well as small MA (P: 68%, NP: 890%), but the maximal relaxation is significantly greater in NP than in P rats (P: 32%, NP: 46%, P < .01) in both vascular beds. In addition, in the UA of P rats, PTHrP only produces relaxation if functional endothelium is present; nevertheless in the absence of endothelium, forskolin still elicits relaxation (65%, P < .01). L-NAME significantly impairs relaxation of E+ UA (P < .05), and so does the association of charybdotoxin + apamin (P < .05). Thus, NO and EDHF contribute largely to this vasorelaxant effect.

Conclusion: PTHrP induces a relaxation on UA that is strongly endothelium-dependent during gestation, in contrast to what happens simultaneously in MA.

Key Words: PTHrP • acetylcholine • rat uterine artery • relaxation • gestation • NO • EDHF


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