The effect of maternal catecholamines on the caliber of gravid uterine microvessels.
BACKGROUND
Changes in maternal catecholamines that accompany the onset of labor analgesia include a decrease in epinephrine (EPI) but no change in norepinephrine (NE). Because EPI exerts predominantly beta-adrenergic, and NE predominantly alpha-adrenergic effects in circulating concentrations, we hypothesized that these changes could lead to uterine arteriole vasoconstriction.


METHODS
Uterine microvessels (73-120 microm internal diameter, n = 18) were harvested from near-term pregnant Sprague-Dawley rats, isolated and studied in a pressurized no-flow state with video microscopy. Drugs were applied extraluminally to the superfusion reservoir and the steady-state vessel diameter recorded. Dose-response curves were constructed for NE with and without the addition of the alpha-adrenergic antagonist prazosin, EPI (after 20%-30% preconstruction with the thromboxane analog U46619) with and without the addition of the beta-adrenergic antagonist propranolol, and NE in the presence of 10(-8) M EPI. Washout experiments modeled the changes in circulating maternal catecholamines observed during onset of analgesia: 10(-8) M EPI and 10(-6.5) M of NE (the EC50) were added simultaneously, then washed with NE only, and then with the beta2-adrenergic agonist terbutaline and NE. The washout protocol was repeated in the presence of propranolol.


RESULTS
NE caused dose-dependent vasoconstriction (P < 0.0001), which was blocked by prazosin (P < 0.0001). EPI, added to U46619-preconstricted microvessels, caused vasodilation at lower concentrations and vasoconstriction at higher doses (P < 0.0001). Propranolol converted this response to monophasic dose-dependent vasoconstriction (P < 0.0001). Pretreatment of nonprecontracted vessels with EPI, 10(-8) M, significantly attenuated NE-induced vasoconstriction (P < 0.0001). In washout experiments, removal of EPI with continued presence of NE resulted in vasoconstriction that was reversed by terbutaline. Propranolol blocked the effect of both EPI and terbutaline.


CONCLUSIONS
The results demonstrate that EPI, in concentrations found in the plasma of laboring women, vasodilates uterine resistance vessels and attenuates NE-induced vasoconstriction. This observation may have implications for changes in uterine blood flow that may accompany the onset of labor analgesia in human parturients, as effective analgesia is accompanied by an acute decrease in circulating EPI levels.
Segal
Scott
S
Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115, USA. bssegal@zeus.bwh.harvard.edu
Wang
Steven Y
SY
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D016362:Analgesia, Obstetrical; D000818:Animals; D001160:Arterioles / Q000378:metabolism; D002395:Catecholamines / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D020073:Gravidity; D009638:Norepinephrine / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D011247:Pregnancy; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013726:Terbutaline / Q000494:pharmacology; D014599:Uterus / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011433:Propranolol; D013726:Terbutaline; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine