The tocolytic effect of catecholamines in the gravid rat uterus.
Maternal catecholamines increase dramatically in labor because of pain and emotional stress. Because the uterus is richly endowed with both alpha- and beta-adrenergic receptors, catecholamines could alter uterine activity. We assessed the effect of clinically encountered concentrations of these catecholamines on uterine activity and modeled the effect of the abrupt reduction in circulating epinephrine that occurs during effective labor analgesia. Term pregnant rat uteri were excised, and cross-sectional rings were mounted for isometric force recording. Log concentration-response curves for epinephrine, norepinephrine, and their combination on uterine activity were constructed from 10(-12) to 10(-6) M. Catecholamine responses were repeated in the presence of phentolamine, an alpha-adrenergic blocker or propranolol, a beta-adrenergic blocker. The abilities of oxytocin and of washout of catecholamines to reverse catecholamine-induced changes in uterine activity were also assessed. Epinephrine caused dose-dependent reductions in uterine activity, blocked by propranolol. Epinephrine concentrations in the clinical range(10(-9) to 10(-8) M; 100-1000 pg/mL) decreased uterine activity to 49.6% +/- 6.6% (mean +/- SE) of control. Norepinephrine caused a dose-dependent increase in uterine activity, which was blocked by phentolamine. In the clinical range (10(-8) M), uterine activity was 139.2% +/- 13.40% of control. The combination of both catecholamines, however, was nearly as tocolytic as epinephrine alone. Oxytocin antagonized catecholamine-induced tocolysis, and washout of epinephrine or both catecholamines increased uterine activity. We conclude that mixed catecholamines are significantly tocolytic at concentrations encountered in laboring women. In this in vitro model, reduction in epinephrine concentration, comparable to that which occurs during effective analgesia, significantly increases uterine activity.


CONCLUSIONS
Maternal catecholamines increase in labor, but epinephrine decreases dramatically after regional analgesia. In this study, we found that norepinephrine and epinephrine together decrease uterine contractile activity and that decreased epinephrine causes significantly increased uterine activity.
Department of Anesthesia Research Laboratories, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. bssegal@zeus.bwh.harvard.edu
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007743:Labor, Obstetric / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology* / Q000502:physiology; D010121:Oxytocin / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011247:Pregnancy; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015149:Tocolytic Agents / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D015149:Tocolytic Agents; D010121:Oxytocin; D011433:Propranolol; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine