Abstract P214: Mechanotransduction And Uterine Blood Flow In Preeclampsia- The Role Of Piezo 1 Ion Channels.

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Olufunke O Arishe ◽  
Vanessa Dela Justina ◽  
Fernanda B Priviero ◽  
Clinton R Webb
Keyword(s):  
Blood Flow ◽  
Vascular Remodeling ◽  
Vascular Reactivity ◽  
Small Diameter ◽  
Subsequent Development ◽  
Normal Pregnancy ◽  
Arterial Blood Flow ◽  
Pregnant Rats ◽  
Arterial Blood

Background: There is a large increase in uterine arterial blood flow during normal pregnancy. Structural and cellular adjustments occur in the uterine vasculature during pregnancy to accommodate this increased blood flow through a process is known as ‘vascular remodeling’. The etiology of preeclampsia involves aberrant placentation and vascular remodeling leading to reduced uteroplacental perfusion. However, the underlying source of the deficient vascular remodeling and the subsequent development of preeclampsia remains to be fully understood. Piezo 1 channels have been shown to be highly expressed in vascular smooth muscle cells of small-diameter arteries and play a role in the structural remodeling of the arteries. Studies have also shown that Piezo 1 is present in uterine arteries and it’s not exclusive to the endothelial cells. Hypothesis: This study tests the hypothesis that reduced Piezo 1 activity contributes to decreased uterine vascular relaxation in hypertensive pregnant rats. Methods: Hypertension was induced by treating the pregnant rats with synthetic CpG ODN (ODN 2395) via three intraperitoneal injections (100μg/rats) while the normotensive controls were treated with saline (vehicle) on the 14 th , 17th and 18 th days of pregnancy. Mean arterial pressure (MAP) was measured. In vitro vascular reactivity of uterine arterial (UA) ring segments were evaluated using isometric wire myograph system. Rings were pre-contracted with 3μM phenylephrine (PE), concentration responses of to Yoda1; a pharmacological agonist of Piezo 1 channel were compared. Statistical analysis was performed using nonlinear regression and Students’ t-test. Results: Our results show that MAP was greater in rats treated with ODN2395 vs untreated rats (112 ± 1 vs 90 ± 1 p =0.0004). Concentration-dependent relaxation responses to Yoda1 were greater in UAs of untreated rats compared to those treated with ODN2395 (EC50 0.06571 ± 0.09781 vs. 0.5774 ± 0.1187 p =0.0018). Conclusion: These results suggest that the reduced vasodilation in pregnancy-associated hypertension may be due to a reduced Piezo 1 channel activity.

scholarly journals Mechanotransduction and Uterine Blood Flow in Preeclampsia: The Role of Mechanosensing Piezo 1 Ion Channels

2019 ◽  
Vol 33 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Olufunke O Arishe ◽  
Anthony B Ebeigbe ◽  
R Clinton Webb
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Vascular Remodeling ◽  
Vascular System ◽  
Perinatal Death ◽  
Small Diameter ◽  
Subsequent Development ◽  
Normal Pregnancy ◽  
Arterial Blood Flow ◽  
Arterial Blood

Abstract There is a large increase in uterine arterial blood flow during normal pregnancy. Structural and cellular adjustments occur in the uterine vasculature during pregnancy to accommodate this increased blood flow through a complex adaptive process that is dependent on multiple coordinated and interactive influences and this process is known as “vascular remodeling.” The etiology of preeclampsia involves aberrant placentation and vascular remodeling leading to reduced uteroplacental perfusion. The placental ischemia leads to development of hypertension and proteinuria in the mother, intrauterine growth restriction, and perinatal death in the fetus. However, the underlying source of the deficient vascular remodeling and the subsequent development of preeclampsia remain to be fully understood. Mechanoreceptors in the vascular system convert mechanical force (shear stress) to biochemical signals and feedback mechanisms. This review focuses on the Piezo 1 channel, a mechanosensitive channel that is sensitive to shear stress in the endothelium; it induces Ca2+ entry which is linked to endothelial nitric oxide synthase (eNOS) activation as the mechanoreceptor responsible for uterine vascular dilatation during pregnancy. Here we describe the downstream signaling pathways involved in this process and the possibility of a deficiency in expression of Piezo 1 in preeclampsia leading to the abnormal vascular dysfunction responsible for the pathophysiology of the disease. The Piezo 1 ion channel is expressed in the endothelium and vascular smooth muscle cells (VSMCs) of small-diameter arteries. It plays a role in the structural remodeling of arteries and is involved in mechanotransduction of hemodynamic shear stress by endothelial cells (ECs).

Relationship between vascular reactivity in vitro and blood flows in rats with cirrhosis

1999 ◽  
Vol 97 (3) ◽  
pp. 313-318 ◽  
Author(s):  
Dominique PATERON ◽  
Frédéric OBERTI ◽  
Pascale LEFILLIATRE ◽  
Nary VEAL ◽  
Khalid A. TAZI ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vascular Reactivity ◽  
Regional Blood Flow ◽  
Arterial Blood Flow ◽  
Blood Flows ◽  
Arterial Blood ◽  
Vascular Responsiveness ◽  
Microsphere Method ◽  
Radioactive Microsphere Method

In cirrhosis there is a hyperdynamic circulation, which occurs mainly in the systemic and splanchnic regions. Using isolated-vessel models, previous studies have shown reduced aortic reactivity to vasoconstrictors in rats with cirrhosis. The aim of the present study was to evaluate and compare the vascular responsiveness to phenylephrine in arterial rings and the blood flows from different regions in rats with cirrhosis and controls. Reactivity was studied in isolated thoracic aortic, superior mesenteric arterial and carotid arterial rings from sham-operated and bile-duct-ligated rats by measuring the cumulative concentration-dependent tension induced by phenylephrine (10-9–10-4 M). Blood flows were measured by the radioactive microsphere method. In rats with cirrhosis, a significant hyporeactivity to phenylephrine was observed in both the aorta and the superior mesenteric artery compared with the corresponding arteries of normal rats. This hyporesponsiveness was corrected by Nω-nitro-l-arginine (0.1 mM). In contrast, carotid artery reactivity and the responses to Nω-nitro-l-arginine were similar in the cirrhotic and control groups. In each case, cardiac output and mesenteric arterial blood flow were significantly higher in cirrhotic than in normal rats. Cerebral blood flows were not significantly different between the two groups. In cirrhotic rats, arterial hyporeactivity may be a consequence of increased regional blood flow and increased production of nitric oxide.

Nitric Oxide and Vascular Reactivity in Pregnant Rats with Adriamycin Nephropathy

1997 ◽  
Vol 93 (3) ◽  
pp. 227-234 ◽  
Author(s):  
Mauro Rathaus ◽  
Eduardo Podjarny ◽  
Sydney Benchetrit ◽  
Janice Green ◽  
Jacques Bernheim
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Vascular Reactivity ◽  
Normal Pregnancy ◽  
Pregnant Rats ◽  
Arterial Blood ◽  
Adriamycin Nephropathy ◽  
Mesenteric Vessels

1. In previous studies we have shown that, after the administration of adriamycin, hypertension developed in rats who became pregnant (adriamycin-pregnant rats), whereas virgin animals remained normotensive. Subsequently, we showed that this hypertension was prevented by administration of l-arginine, suggesting that deficient synthesis of nitric oxide may be pathogenetic in this model. 2. To further assess the role of nitric oxide in this model, we measured mean arterial blood pressure after administration of l-arginine to adriamycin-pregnant rats or of NG-nitro-l-arginine-methyl ester (l-NAME) to normal pregnant rats. In other experiments, we assessed the response of isolated perfused arterial mesenteric vessels, precontracted with noradrenaline, to acetylcholine, l-arginine or l-NAME. 3. Blood pressure was decreased in normal pregnant rats, whereas it was elevated in adriamycin-pregnant rats. l-NAME treatment increased blood pressure in normal pregnant rats and l-arginine decreased it in adriamycin-pregnant rats. 4. Mesenteric vessels of adriamycin-pregnant rats exibited an exaggerated vasoconstrictory response to noradrenaline, when compared with the blunted response observed in normal pregnancy. The addition of l-NAME in vitro induced a further contraction, significantly greater in normal pregnant rats. The vasodilatory response to acetylcholine and l-arginine was greater in vessels from adriamycin-pregnant rats. In contrast, responses to either nitroprusside or diazoxide were similar in all groups. 5. The results suggest a state of reduced nitric oxide synthesis in rats with adriamycin nephropathy, leading to vascular maladaption and hypertension in pregnancy.

A new method for visualizing pulmonary artery microvasculature using synchrotron radiation pulmonary microangiography: the measurement of pulmonary arterial blood flow velocity in the high pulmonary blood flow rat model

2018 ◽  
Vol 59 (12) ◽  
pp. 1482-1486 ◽  
Author(s):  
Chiho Tokunaga ◽  
Shonosuke Matsushita ◽  
Hiroaki Sakamoto ◽  
Kazuyuki Hyodo ◽  
Misao Kubota ◽  
...  
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Synchrotron Radiation ◽  
Pulmonary Artery ◽  
Rat Model ◽  
Vascular Remodeling ◽  
Pulmonary Blood Flow ◽  
Arterial Blood Flow ◽  
Non Invasive ◽  
Arterial Blood

Background Increased pulmonary blood flow (PBF) and shear stress may provoke irreversible vascular remodeling, yet invasive visualization of the microvasculature complicates monitoring. A non-invasive imaging methodology would therefore safely provide mechanistic insights into the progression of high PBF-induced vascular remodeling. Purpose To establish a novel microvasculature visualization method using synchrotron radiation pulmonary microangiography (SRPA) that can also calculate PBF velocity in vivo. Material and Methods A high PBF rat model was established by making a fistula between the abdominal aorta and inferior vena cava. After eight weeks, SRPA was performed and the dynamic density changes in the right lower pulmonary artery (PA) were calculated by software. SRPA was performed with a HARP (High-Gain Avalanche Rushing amorphous Photoconductor) receiver. PBF velocity was calculated by contrast medium transit time within the PA. All data were presented as mean ± standard error (SE). Student's t-test was used for comparison between the two groups. Results High dynamic spatial and contrast resolution from SRPA in the PA allowed for clear pulmonary microangiography and accurate detection of higher PBF in the rat model (82.3 ± 8.5 mm/s high-PBF group vs. 46.1 ± 4.3 mm/s control group, P < 0.01). Conclusions These novel results demonstrate that SRPA was useful in both visualizing the dynamic flow distribution within the microvasculature and calculating PBF velocity. This newly developed, non-invasive technology may become a powerful tool in clarifying the mechanism of vascular remodeling associated with high PBF-induced shear stress.

scholarly journals Endothelial miR-17∼92 cluster negatively regulates arteriogenesis via miRNA-19 repression of WNT signaling

2015 ◽  
Vol 112 (41) ◽  
pp. 12812-12817 ◽  
Author(s):  
Shira Landskroner-Eiger ◽  
Cong Qiu ◽  
Paola Perrotta ◽  
Mauro Siragusa ◽  
Monica Y. Lee ◽  
...  
Keyword(s):  
Blood Flow ◽  
Wnt Signaling ◽  
Critical Role ◽  
Arterial Blood Flow ◽  
In Vivo Model ◽  
Mirna Regulation ◽  
Arterial Blood ◽  
Specific Deletion

The contribution of endothelial-derived miR-17∼92 to ischemia-induced arteriogenesis has not been investigated in an in vivo model. In the present study, we demonstrate a critical role for the endothelial-derived miR-17∼92 cluster in shaping physiological and ischemia-triggered arteriogenesis. Endothelial-specific deletion of miR-17∼92 results in an increase in collateral density limbs and hearts and in ischemic limbs compared with control mice, and consequently improves blood flow recovery. Individual cluster components positively or negatively regulate endothelial cell (EC) functions in vitro, and, remarkably, ECs lacking the cluster spontaneously form cords in a manner rescued by miR-17a, -18a, and -19a. Using both in vitro and in vivo analyses, we identified FZD4 and LRP6 as targets of miR-19a/b. Both of these targets were up-regulated in 17∼92 KO ECs compared with control ECs, and both were shown to be targeted by miR-19 using luciferase assays. We demonstrate that miR-19a negatively regulates FZD4, its coreceptor LRP6, and WNT signaling, and that antagonism of miR-19a/b in aged mice improves blood flow recovery after ischemia and reduces repression of these targets. Collectively, these data provide insights into miRNA regulation of arterialization and highlight the importance of vascular WNT signaling in maintaining arterial blood flow.

scholarly journals Blood flow-induced Notch activation and endothelial migration enable embryonic vascular remodeling

2016 ◽  
Author(s):  
Bart Weijts ◽  
Edgar Gutierrez ◽  
Semion K Saikin ◽  
Ararat J Ablooglu ◽  
David Traver ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vascular Remodeling ◽  
Venous Blood ◽  
Arterial Blood Flow ◽  
Venous Blood Flow ◽  
Upstream Migration ◽  
Venous Circulation ◽  
Arterial Blood ◽  
Arteries And Veins ◽  
Notch Activation

Arteries and veins are formed independently by different types of endothelial cells (ECs). In vascular remodeling, arteries and veins become connected and some arteries become veins. It is unclear how ECs in transforming vessels change their type and how fates of individual vessels are determined. In embryonic trunk, vascular remodeling transforms arterial intersegmental vessels (ISVs) into a functional network of arteries and veins. We found that, once an ISV is connected to venous circulation, venous blood flow promotes upstream migration of ECs that results in displacement of arterial ECs by venous ECs, completing the transformation of this ISV into a vein without trans-differentiation of ECs. Arterial blood flow initiated in two neighboring ISVs prevents their transformation into veins by activating Notch signaling in ECs. Together, different responses of ECs to arterial and venous blood flow lead to the formation of a balanced network with equal numbers of arteries and veins.

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