Local Uteroplacental Influences are Responsible for the Induction of Uterine Artery Myogenic Tone during Rat Pregnancy

Uterine artery constrictor responses to elevation of intraluminal pressure (myogenic tone) are considerably enhanced in late pregnant rats, although the underlying causes remain unknown. A single uterine horn ligation model was used to differentiate local from systemic influences, and to test the hypothesis that factors associated with the site of placentation, rather than systemic hormonal changes, are primarily involved in the induction of this adaptive process. Radial uterine arteries were dissected from the gravid and nongravid uterine horns of late pregnant rats, cannulated, and pressurized. Changes in arterial diameter and smooth muscle [Ca(2+)](i) in response to the elevation of intraluminal pressure were studied using intact and endothelium-denuded arteries loaded with the ratiometric Ca(2+)-sensitive dye fura-2. Elevations of pressure from 10 to 60 and 100 mm Hg resulted in passive arterial distention of arteries from nongravid horns with a minor change in [Ca(2+)](i). In contrast, arteries from gravid horns developed myogenic tone associated with a significant elevation in [Ca(2+)](i). Synchronous oscillations in [Ca(2+)](i) and lumen diameter were frequently observed in vessels from gravid horns. Endothelial denudation augmented tone in the gravid horn but did not uncover myogenic tone in vessels from the nongravid horn. In summary, pregnancy-associated uterine artery myogenic behavior is due to an upregulation of calcium-handling mechanisms, occurs independently of the endothelium, and is induced by local uteroplacental influences.