|Abstract or Summary
- The role of estradiol- 17β, progesterone and prostaglandin F₂α (PGF₂α) in altering contractility of uterine vascular smooth muscle was investigated. A segment of uterine artery (3. 5 cm) supplying each uterine horn of ewes and heifers were removed at necropsy and perfused with oxygenated Krebs Henseleit Solution prior to initiating sequential drug perfusions. Arteries were subjected to electrical stimulation (ES) and changes in perfusion pressure due to changes in resistance to flow were recorded in mm Hg. EXPERIMENT I: Uterine arteries from unilaterally-ovulating pregnant (P) and nonpregnant (NP) ewes and heifers, necropsied on days 15 and 17 post-estrus, respectively, (estrus=day 0) were subjected to three 30 min perfusions in the order: saline, PGF₂α (1 ng/ ml) and saline. Overall, responsiveness to ES by arteries ipsilateral to ovaries bearing corpora lutea (CL) from both species was greater (P <. 01) than that of contralateral arteries in NP animals only. Arteries from NP ewes and heifers perfused with PGF₂α exhibited greater (P <. 05) smooth muscle contractility in response to ES than when arteries were perfused with saline. Perfusion of arteries from P animals with PGF₂α resulted in no change (heifers) or a decrease (P <. 05) in contractility (ewes) to ES when compared to responses of arteries to ES during saline perfusions. Perfusion of arteries from NP ewes with conceptus brei (conceptuses of day 15 P ewes) for 30 min, caused a marked decrease (P <. 01) in contractility of arteries to ES during a subsequent perfusion of PGF₂α. EXPERIMENT II: Five unilaterally-ovulating NP ewes were sacrificed on each of days 0 (estrus), 3, 6 and 10 of the estrous cycle. Regardless of stage studied, uterine arteries ipsilateral to ovaries having the greater follicular development, hereafter referred to as ipsilateral arteries, responded to ES with increased smooth muscle contractility when compared to the low consistent responses of contralateral arteries. Responses of ipsilateral arteries to ES following perfusions of saline, PGF₂α or norepinephrine (NE) increased from day 0 to 10 of the cycle. However, only ipsilateral arteries from day- 10 ewes exhibited increased (P <. 01) contractility to ES following perfusion of PGF₂α. Perfusion of phentolamine reduced contractility (P <. 01) of ips:lateral arteries to ES when compared to responses after previous perfusions of saline, PGF₂α or NE. Subsequent perfusion of PGF₂α failed to increase arterial response to ES over that exh'ibIted following phentolamine perfusion. Perfusion of ipsilateral arteries with NE after PGF₂α resulted in a return of smooth muscle contractility to ES (P <. 01). EXPERIMENT III: Sixteen ovariectomized ewes were assigned randomly to four groups and received the following treatments for one week: 1) none (controls); 2) estradiol- 17β (E₂, 54 mg implant); 3) progesterone (P4, 15 mg twice daily); and 4) E₂ + P₄. Treatment of ewes with P4 increased (P <. 01) while treatment with E ₂ decreased (P <. 01) arterial smooth muscle contraction to ES following initial perfusions of saline, PGF₂α or NE compared to responses of arteries removed from control or E₂ + P ₄-treated ewes. Responses of arteries from control and E ₂ + P ₄-treated ewes did not differ. Arteries from all ewes exhibited increased contractility (P <. 01) to ES following NE when compared to responses evoked by ES following perfusions of saline or PGF₂α. Perfusion of phentolamine depressed smooth muscle contraction (P <-. 01) of arteries of all ewes. Subsequent perfusion of PGF₂α failed to elicit an increase in arterial contractility to ES over that exhibited following phentolamine perfusion. Arteries from all ewes except those treated with E2 responded to ES with increasing contraction of smooth muscle following repeated perfusions of NE after PGF₂α. It is proposed that progesterone and estradiol alter uterine arterial nerve concentration of NE and/or sensitivity of smooth muscle cells, and thus, in concert with the regulatory action of PGF₂α on the release of NE, may serve to modulate arterial smooth muscle contractility.