Parathyroid hormone-related protein-induced relaxation of rat uterine arteries: influence of the endothelium during gestation.
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, and forskolin were performed 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 Nomega-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: 46%), as well as small MA (P: 68%, NP: 89%), 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.


CONCLUSIONS
PTHrP induces a relaxation on UA that is strongly endothelium-dependent during gestation, in contrast to what happens simultaneously in MA.
Meziani
Ferhat
F
Physicochimie des Interactions Cellulaires et Moléculaires, CNRS UMR 7034, Université Louis Pasteur, Strasbourg, France.
Van Overloop
Bruno
B
Schneider
Francis
F
Gairard
Alexis
A
D000818:Animals; D004727:Endothelium / Q000502:physiology; D005260:Female; D008638:Mesenteric Arteries / Q000502:physiology; D009215:Myometrium / Q000098:blood supply*; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology*; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000098:blood supply* / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*
D044162:Parathyroid Hormone-Related Protein