Increased vascular angiotensin type 2 receptor expression and NOS-mediated mechanisms of vascular relaxation in pregnant rats
| Autor: | Amanda K. Stennett, Vera V. Koledova, Xiaoying Qiao, Raouf A. Khalil, Anthony Falone |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Angiotensin receptor
medicine.medical_specialty Vascular smooth muscle Endothelium Nitric Oxide Synthase Type III Physiology Pyridines Vasodilator Agents Hemodynamics Vasodilation Blood Pressure Biology Nitric Oxide Receptor Angiotensin Type 2 Losartan Muscle Smooth Vascular Receptor Angiotensin Type 1 Rats Sprague-Dawley Phenylephrine Pregnancy Physiology (medical) Internal medicine medicine Animals Vasoconstrictor Agents RNA Messenger Phosphorylation Aorta Dose-Response Relationship Drug Angiotensin II Imidazoles Articles Acetylcholine Rats Up-Regulation medicine.anatomical_structure Endocrinology Vasoconstriction Female Endothelium Vascular medicine.symptom Cardiology and Cardiovascular Medicine Angiotensin II Type 1 Receptor Blockers Oligopeptides medicine.drug |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 296(3) |
| ISSN: | 0363-6135 |
| Popis: | Normal pregnancy is associated with reduced blood pressure (BP) and decreased pressor response to vasoconstrictors, even though the renin-angiotensin system is upregulated. Angiotensin II (ANG II) activates both angiotensin type 1 receptors (AT1Rs) and angiotensin type 2 receptors (AT2Rs). Although the role of the AT1R in vascular contraction is well documented, the role of the AT2R in vascular relaxation, particularly during pregnancy, is less clear. It was hypothesized that the decreased BP and vasoconstriction during pregnancy was, at least in part, due to changes in AT2R amount, distribution, and/or postreceptor mechanisms of vascular relaxation. To test this hypothesis, systolic BP was measured in virgin and pregnant ( day 19) Sprague-Dawley rats. Isometric contraction/relaxation was measured in isolated aortic rings, and nitric oxide (NO) production was measured using 4-amino-5-methylamino-2′,7′-difluorescein fluorescence. AT1R and AT2R mRNA expression and protein amount were measured in tissue homogenates using real-time RT-PCR and Western blots, and their local distribution was visualized in cryosections using immunohistochemistry and immunofluorescence. BP was lower in pregnant than virgin rats. Phenylephrine (Phe) caused concentration-dependent contraction that was reduced in the aorta of pregnant compared with virgin rats. Treatment with the AT2R antagonist PD-123319 caused greater enhancement of Phe contraction, and the AT2R agonist CGP-42112A caused greater relaxation of Phe contraction in the aorta of pregnant than virgin rats. ANG II plus the AT1R blocker losartan induced greater NO production in the aorta of pregnant than virgin rats. RT-PCR revealed increased mRNA expression of vascular endothelial NO synthase (eNOS), little change in AT1Rs, and increased AT2Rs in pregnant compared with virgin rats. Western blots revealed an increased protein amount of activated phospho-eNOS, little change in AT1Rs, and increased AT2Rs in pregnant compared with virgin rats. Immunohistochemistry and immunofluorescence analysis in aortic sections of virgin rats revealed abundant AT1R staining in tunica media that largely colocalized with actin in vascular smooth muscle and less AT2Rs mainly in the tunica intima and endothelium. In pregnant rats, AT1R staining in the smooth muscle layer and adventitia was reduced, and endothelial AT2R staining was enhanced. These data suggest an enhanced AT2R-mediated vascular relaxation pathway involving increased expression/activity of endothelial AT2Rs and increased postreceptor activated phospho-eNOS, which may contribute to the decreased BP during pregnancy. |
| Databáze: | OpenAIRE |
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