Back to Search
Start Over
Defining the differential sensitivity to norepinephrine and angiotensin II in the ovine uterine vasculature.
- Source :
-
American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2012 Jan 01; Vol. 302 (1), pp. R59-67. Date of Electronic Publication: 2011 Oct 26. - Publication Year :
- 2012
-
Abstract
- The intact ovine uterine vascular bed (UVB) is sensitive to α-agonists and refractory to angiotensin II (ANG II) during pregnancy; the converse occurs in the systemic circulation. The mechanism(s) responsible for these differences in uterine sensitivity are unclear and may reflect predominance of nonconstricting AT(2) receptors (AT(2)R) in uterine vascular smooth muscle (UVSM). The contribution of the placental vasculature also is unclear. Third generation and precaruncular/placental arteries from nonpregnant (n = 16) and term pregnant (n = 23) sheep were used to study contraction responses to KCl, norepinephrine (NE), and ANG II (with/without ATR specific inhibitors) and determine UVSM ATR subtype expression and contractile protein content. KCl and NE increased third generation and precaruncular/placental UVSM contractions in a dose- and pregnancy-dependent manner (P ≤ 0.001). ANG II only elicited modest contractions in third generation pregnant UVSM (P = 0.04) and none in precaruncular/placental UVSM. Moreover, compared with KCl and NE, ANG II contractions were diminished ≥ 5-fold. Whereas KCl and ANG II contracted third generation>>precaruncular/placental UVSM, NE-induced contractions were similar throughout the UVB. However, each agonist increased third generation contractions ≥ 2-fold at term, paralleling increased actin/myosin and cellular protein content (P ≤ 0.01). UVSM AT(1)R and AT(2)R expression was similar throughout the UVB and unchanged during pregnancy (P > 0.1). AT(1)R inhibition blocked ANG II-mediated contractions; AT(2)R blockade, however, did not enhance contractions. AT(2)R predominate throughout the UVB of nonpregnant and pregnant sheep, contributing to an inherent refractoriness to ANG II. In contrast, NE elicits enhanced contractility throughout the ovine UVB that exceeds ANG II and increases further at term pregnancy.
- Subjects :
- Animals
Arteries metabolism
Dose-Response Relationship, Drug
Female
Models, Animal
Muscle Contraction drug effects
Muscle, Smooth, Vascular metabolism
Potassium Chloride pharmacology
Pregnancy
Receptor, Angiotensin, Type 1 metabolism
Receptor, Angiotensin, Type 2 metabolism
Sheep
Vasoconstriction physiology
Angiotensin II pharmacology
Arteries drug effects
Muscle, Smooth, Vascular drug effects
Norepinephrine pharmacology
Uterus blood supply
Vasoconstriction drug effects
Vasoconstrictor Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1490
- Volume :
- 302
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Regulatory, integrative and comparative physiology
- Publication Type :
- Academic Journal
- Accession number :
- 22031783
- Full Text :
- https://doi.org/10.1152/ajpregu.00424.2011