221. Localisation of relaxin receptors (Rxfp1) in the uterine artery and the effects of blocking circulating relaxin on passive mechanical wall properties in the uterine artery of late pregnant rats

2008 ◽  
Vol 20 (9) ◽  
pp. 21
Author(s):  
L. A. Vodstrcil ◽  
J. Novak ◽  
M. Tare ◽  
M. E. Wlodek ◽  
L. J. Parry
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Uterine Artery ◽  
Late Pregnancy ◽  
Artery Wall ◽  
Pregnant Rats ◽  
Uterine Arteries ◽  
Wall Properties ◽  
Wall Stiffness

During pregnancy, the uteroplacental circulation undergoes dramatic alterations to allow for the large increase in blood flow to the feto-placental unit. These alterations are achieved through several mechanisms including structural changes in the uterine artery wall and endothelium-dependent vasodilation. Small renal arteries of relaxin-deficient mice and rats have enhanced myogenic reactivity and decreased passive compliance, and are relatively vasoconstricted (Novak et al. 2001, 2006). To date, no study has identified relaxin receptors (Rxfp1) in arteries or investigated the effects of relaxin deficiency in pregnancy on uterine artery function. The aims of this current study were to: 1) localise Rxfp1 in the uterine arteries, 2) measure myogenic reactivity in small uterine arteries after relaxin treatment, and 3) test the hypothesis that blocking circulating relaxin in late pregnancy will increase uterine artery wall stiffness. We demonstrated that Rxfp1 is expressed in the uterine arteries of pregnant mice and rats. Brightfield immunohistochemistry and immunofluorescence using antibodies specific for rat Rxfp1, α-smooth muscle actin and CD31 localised Rxfp1 protein predominantly to the vascular smooth muscle in the uterine artery of pregnant rats. Administration of recombinant human H2 relaxin (4 ug/h) for 6 h or 5 days in intact and ovariectomised rats reduced myogenic reactivity of small uterine arteries in vitro. Pregnant rats were treated with a monoclonal antibody against circulating relaxin (MCA1) or control (MCAF) for 3 days (Days 17–19) and uterine arteries were mounted on a pressure myograph to assess passive mechanical wall properties. Neutralising circulating relaxin in late pregnancy resulted in a significant increase in uterine artery wall stiffness. These data demonstrate that relaxin acts on the vascular smooth muscle cells in the uterine artery and may be involved in the pregnancy-specific vascular remodelling of uterine arteries to increase vasodilation and blood flow to the uterus and placenta. (1) Novak J et al. (2001). J Clin Invest 107: 1469–75 (2) Novak J et al. (2006). FASEB J 20: 2352–62

scholarly journals Augmented dilation to nitric oxide in uterine arteries from rats with type 2 diabetes: implications for vascular adaptations to pregnancy

2014 ◽  
Vol 306 (4) ◽  
pp. H610-H618 ◽  
Author(s):  
Styliani Goulopoulou ◽  
Johanna L. Hannan ◽  
Takayuki Matsumoto ◽  
Adviye Ergul ◽  
R. Clinton Webb
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Soluble Guanylate Cyclase ◽  
Vascular Dysfunction ◽  
Late Pregnancy ◽  
Gk Rats ◽  
Uterine Arteries

Pre-existing diabetes increases the risk of maternal and fetal complications during pregnancy, which may be due to underlying maternal vascular dysfunction and impaired blood supply to the uteroplacental unit. Endothelial dysfunction and reduced vascular smooth muscle responsiveness to nitric oxide (NO) are common vascular impairments in type 2 diabetes (T2D). We hypothesized that uterine arteries from diabetic rats would have reduced vascular smooth muscle sensitivity to NO compared with nondiabetic rats due to impairment in the NO/soluble guanylate cyclase (sGC)/cGMP signaling pathway. Uterine arteries from pregnant Goto-Kakizaki (GK; model of T2D) and Wistar (nondiabetic) rats were studied in a wire myograph. GK nonpregnant uterine arteries had reduced responses to ACh and sodium nitroprusside (SNP) but increased responses to propylamine propylamine NONOate and greater sensitivity to sildenafil compared with Wistar nonpregnant arteries. In late pregnancy, Wistar rats had reduced uterine vascular smooth muscle responsiveness to SNP, but GK rats failed to show this adaptation and had reduced expression of sGC compared with the nonpregnant state. GK rats had a smaller litter size (13.9 ± 0.48 vs. 9.8 ± 0.75; P < 0.05) and a greater number of resorptions compared with Wistar controls (0.8 ± 0.76% vs. 19.9 ± 6.06%; P < 0.05). These results suggest that uterine arteries from rats with T2D show reduced sensitivity of uterine vascular smooth muscle sGC to NO. During pregnancy, the GK uterine vascular smooth muscle fails to show relaxation responses similar to those of arteries from nondiabetic rats.

Ca2+-activated K+ channels modulate basal and E2β-induced rises in uterine blood flow in ovine pregnancy

2001 ◽  
Vol 281 (1) ◽  
pp. H422-H431 ◽  
Author(s):  
Charles R. Rosenfeld ◽  
David N. Cornfield ◽  
Timothy Roy
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Uterine Artery ◽  
Late Pregnancy ◽  
Uterine Blood Flow ◽  
Calcium Dependent ◽  
Uterine Arteries ◽  
Near Term ◽  
Artery Flow ◽  
Oxide Synthase

Uterine blood flow (UBF) increases >30-fold during ovine pregnancy. During the last trimester, this reflects vasodilation, which may be due to placentally derived estrogens. In nonpregnant ewes, estradiol-17β (E2β) increases UBF >10-fold by activating nitric oxide synthase and large conductance calcium-dependent potassium channels (BKCa). To determine whether BKCa channels modulate basal and E2β-induced increases in UBF, studies were performed in near-term pregnant ewes with uterine artery flow probes and catheters for intra-arterial infusions of tetraethylammonium (TEA), a selective BKCa channel antagonist at <1 mM, in the absence or presence of E2β (1 μg/kg iv). Uterine arteries were collected to measure BKCa channel mRNA. TEA (0.15 mM) decreased basal UBF ( P < 0.0001) 40 ± 8% and 55 ± 7% ( n = 11) at 60 and 90 min, respectively, and increased resistance 175 ± 48% without affecting ( P > 0.1) mean arterial pressure (MAP), heart rate, or contralateral UBF. Systemic E2β increased UBF 30 ± 6% and heart rate 13 ± 1% ( P ≤ 0.0001, n = 13) without altering MAP. Local TEA (0.15 mM) inhibited E2β-induced increases in UBF without affecting increases in heart rate (10 ± 4%; P = 0.006). BKCa channel mRNA was present in uterine artery myocytes from pregnant and nonpregnant ewes. Exponential increases in ovine UBF in late pregnancy may reflect BKCa channel activation, which may be mediated by placentally derived estrogens.

scholarly journals Adrenergic airway vascular smooth muscle responsiveness in healthy and asthmatic subjects

2001 ◽  
Vol 90 (2) ◽  
pp. 665-669 ◽  
Author(s):  
Jorge Brieva ◽  
Adam Wanner
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Dead Space ◽  
Healthy Subjects ◽  
Contractile Response ◽  
Mucosal Blood Flow ◽  
Forced Expiratory Volume ◽  
Baseline Values ◽  
The Mean

The purpose of the present study was to determine the responsiveness of airway vascular smooth muscle (AVSM) as assessed by airway mucosal blood flow (Q˙aw) to inhaled methoxamine (α1-agonist; 0.6–2.3 mg) and albuterol (β2-agonist; 0.2–1.2 mg) in healthy [ n = 11; forced expiratory volume in 1 s, 92 ± 4 (SE) % of predicted] and asthmatic ( n = 11, mean forced expiratory volume in 1 s, 81 ± 5%) adults. Mean baseline values for Q˙aw were 43.8 ± 0.7 and 54.3 ± 0.8 μl · min−1· ml−1of anatomic dead space in healthy and asthmatic subjects, respectively ( P < 0.05). After methoxamine inhalation, the maximal mean change in Q˙aw was −13.5 ± 1.0 μl · min−1· ml−1in asthmatic and −7.1 ± 2.1 μl · min−1· ml−1in healthy subjects ( P < 0.05). After albuterol, the mean maximal change in Q˙aw was 3.0 ± 0.8 μl · min−1· ml−1in asthmatic and 14.0 ± 1.1 μl · min−1· ml−1in healthy subjects ( P < 0.05). These results demonstrate that the contractile response of AVSM to α1-adrenoceptor activation is enhanced and the dilator response of AVSM to β2-adrenoceptor activation is blunted in asthmatic subjects.

Regulation of types I and III NOS in ovine uterine arteries by daily and acute estrogen exposure

2000 ◽  
Vol 278 (6) ◽  
pp. H2134-H2142 ◽  
Author(s):  
Walid A. Salhab ◽  
Philip W. Shaul ◽  
Blair E. Cox ◽  
Charles R. Rosenfeld
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Smooth Muscle ◽  
Nitric Oxide Synthases ◽  
Uterine Blood Flow ◽  
Calcium Dependent ◽  
Uterine Arteries ◽  
Estrogen Exposure ◽  
The Media ◽  
Estradiol 17Β

Nitric oxide contributes to estrogen-mediated uterine vasodilation; however, the nitric oxide synthases (NOS) involved and their location within uterine arteries are incompletely documented. We investigated the effects of repetitive daily and acute estradiol-17β (E2β) exposure on uterine hemodynamics and NOS abundance and localization in uterine arteries from nonpregnant ovariectomized ewes receiving daily intravenous E2β (1 μg/kg, n = 5) or no E2β ( n = 7) for 5 days to determine NOS abundance, cGMP contents, and NOS immunohistochemistry. Daily E2β increased basal and E2β-mediated rises in uterine blood flow (UBF) 36 and 43% (<0.01), respectively, calcium-dependent NOS activity 150% ( P < 0.02) in endothelium-intact and -denuded (∼40% of total NOS) arteries, and cGMP contents 39% ( P < 0.05). Endothelial (eNOS) was detected in luminal endothelium, whereas neuronal NOS (nNOS) protein was only in the media. A second group of ewes received E2β (1 μg/kg iv) for 4 days and acute intravenous E2β ( n = 8) or vehicle ( n= 4) on day 5. UBF rose 5.5-fold ( P < 0.001) 115 min after E2β, at which time only endothelium-derived calcium-dependent NOS activity increased 30 ± 13% ( P < 0.05). Daily E2β enhances basal and E2β-mediated increases in UBF, which parallel increases in endothelium-derived eNOS and smooth muscle-derived nNOS. Acute E2β, however, selectively increases endothelium-derived eNOS.

scholarly journals Bexarotene Exerts Protective Effects Through Modulation of the Cerebral Vascular Smooth Muscle Cell Phenotypic Transformation by Regulating PPARγ/FLAP/LTB4 After Subarachnoid Hemorrhage in Rats

2019 ◽  
Vol 28 (9-10) ◽  
pp. 1161-1172 ◽  
Author(s):  
Zhaosi Zhang ◽  
Guosheng Zhao ◽  
Liu Liu ◽  
Junchi He ◽  
Rami Darwazeh ◽  
...  
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Vascular Smooth Muscle ◽  
Neurological Impairment ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Cortical Blood Flow ◽  
Phenotypic Transformation ◽  
Cerebral Cortical Blood Flow

Vascular smooth muscle cells (VSMCs) play an important role after a subarachnoid hemorrhage (SAH). The changes in VSMCs following bexarotene treatment after SAH are unknown. In the present study, neurological impairment, decreased cerebral cortical blood flow and transformation of cerebral VSMCs from a contractile to a synthetic phenotype were observed after SAH. Bexarotene reduced neurological impairment, improved cerebral cortical blood flow, inhibited VSMC phenotypic transformation and suppressed the expression of 5-lipoxygenase-activating protein (FLAP) and leukotriene B4 (LTB4), which was partly reversed by GW9662, an inhibitor of peroxisome proliferator-activated receptor gamma (PPARγ). Mechanistically, sh-PPARγ-mediated phenotypic transformation of VSMCs was partially suppressed by MK886, an antagonist of FLAP. Therefore, we conclude that bexarotene reduced neurological impairment, improved cerebral cortical blood flow and inhibited the VSMC phenotypic transformation after SAH, which was achieved by activating PPARγ-mediated inhibition of FLAP/LTB4 in VSMCs

Decreased function of voltage-gated potassium channels contributes to augmented myogenic tone of uterine arteries in late pregnancy

2008 ◽  
Vol 294 (1) ◽  
pp. H272-H284 ◽  
Author(s):  
Vsevolod Telezhkin ◽  
Tara Goecks ◽  
Adrian D. Bonev ◽  
George Osol ◽  
Natalia I. Gokina
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Late Pregnancy ◽  
Intraluminal Pressure ◽  
Delayed Rectifier ◽  
Myogenic Tone ◽  
Channel Activity ◽  
Voltage Gated ◽  
Uterine Arteries ◽  
Increased Pressure

Increased pressure-induced (myogenic) tone in small uteroplacental arteries from late pregnant (LP) rats has been previously observed. In this study, we hypothesized that this response may result from a diminished activity of vascular smooth muscle cell (SMC) voltage-gated delayed-rectifier K+ (Kv) channels, leading to membrane depolarization, augmented Ca2+ influx, and vasoconstriction (tone). Elevation of intraluminal pressure from 10 to 60 and 100 mmHg resulted in a marked, diltiazem-sensitive rise in SMC cytosolic Ca2+ concentration ([Ca2+]i) associated with a vasoconstriction of uteroplacental arteries of LP rats. In contrast, these changes were significantly diminished in uterine arteries from nonpregnant (NP) rats. Gestational augmentation of pressure-induced Ca2+ influx through L-type Ca2+ channels was associated with an enhanced SMC depolarization, the appearance of electrical and [Ca2+]i oscillatory activities, and vasomotion. Exposure of vessels from NP animals to 4-aminopyridine, which inhibits the activity of Kv channels, mimicked the effects of pregnancy by increasing pressure-induced depolarization, elevation of [Ca2+]i, and development of myogenic tone. Furthermore, currents through Kv channels were significantly reduced in myocytes dissociated from arteries of LP rats compared with those of NP controls. Based on these results, we conclude that decreased Kv channel activity contributes importantly to enhanced pressure-induced depolarization, Ca2+ entry, and increase in myogenic tone present in uteroplacental arteries from LP rats.

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