scholarly journals Elevated aldosterone and blood pressure in a mouse model of familial hyperaldosteronism with ClC-2 mutation

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Julia Schewe ◽  
Eric Seidel ◽  
Sofia Forslund ◽  
Lajos Marko ◽  
Jörg Peters ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mouse Model ◽  
Oscillatory Activity ◽  
Type Ii ◽  
Mild Form ◽  
Familial Hyperaldosteronism ◽  
Aldosterone Production ◽  
Knockout Model ◽  
Knockin Mouse

AbstractGain-of-function mutations in the chloride channel ClC-2 were recently described as a cause of familial hyperaldosteronism type II (FH-II). Here, we report the generation of a mouse model carrying a missense mutation homologous to the most common FH-II-associated CLCN2 mutation. In these Clcn2R180Q/+ mice, adrenal morphology is normal, but Cyp11b2 expression and plasma aldosterone levels are elevated. Male Clcn2R180Q/+ mice have increased aldosterone:renin ratios as well as elevated blood pressure levels. The counterpart knockout model (Clcn2−/−), in contrast, requires elevated renin levels to maintain normal aldosterone levels. Adrenal slices of Clcn2R180Q/+ mice show increased calcium oscillatory activity. Together, our work provides a knockin mouse model with a mild form of primary aldosteronism, likely due to increased chloride efflux and depolarization. We demonstrate a role of ClC-2 in normal aldosterone production beyond the observed pathophysiology.

Role of Prostacyclin in Blood Pressure Regulation and Aldosterone Production in Conscious Rabbits

1984 ◽  
Vol 66 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Isamu Miyamori ◽  
Toshio Morise ◽  
Masatoshi Ikeda ◽  
Hideo Koshida ◽  
Yoshiyu Takeda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Blood Pressure Response ◽  
Control Level ◽  
Ang Ii ◽  
Pressure Regulation ◽  
Aldosterone Production ◽  
Hormonal Action ◽  
Conscious Rabbits

1. The effects of subdepressor infusion of prostacyclin (PGI2, 5.3 pmol min−1 kg−1) on arterial pressure and aldosterone production induced by angiotensin II (ANG II) were studied in conscious rabbits. 2. Indomethacin pretreatment caused an augmented blood pressure response after ANG II infusion, which returned to near control level after concomitant infusion of a subdepressor dose of PGI2. 3. Aldosterone production after ANG II was significantly attenuated after pretreatment with indomethacin. PGI2 infusion restored this reduced response to near control level. 4. These results may suggest that PGI2 in the circulation could also serve to modulate the pressor and hormonal action(s) of ANG II.

scholarly journals Generation and Application of Inducible Chimeric RNA ASTN2-PAPPAas Knockin Mouse Model

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 277
Author(s):  
Yichen Luo ◽  
Liang Du ◽  
Zhimeng Yao ◽  
Fan Liu ◽  
Kai Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Mouse Model ◽  
Mouse Genome ◽  
Chemical Carcinogen ◽  
Diagnosis And Prognosis ◽  
Chimeric Rnas ◽  
Chimeric Rna ◽  
Biochemical Indices ◽  
Knockin Mouse

Chimeric RNAs (chiRNAs) play many previously unrecognized roles in different diseases including cancer. They can not only be used as biomarkers for diagnosis and prognosis of various diseases but also serve as potential therapeutic targets. In order to better understand the roles of chiRNAs in pathogenesis, we inserted human sequences into mouse genome and established a knockin mouse model of the tamoxifen-inducible expression of ASTN2-PAPPA antisense chimeric RNA (A-PaschiRNA). Mice carrying the A-PaschiRNA knockin gene do not display any apparent abnormalities in growth, fertility, histological, hematopoietic, and biochemical indices. Using this model, we dissected the role of A-PaschiRNA in chemical carcinogen 4-nitroquinoline 1-oxide (4NQO)-induced carcinogenesis of esophageal squamous cell carcinoma (ESCC). To our knowledge, we are the first to generate a chiRNA knockin mouse model using the Cre-loxP system. The model could be used to explore the roles of chiRNA in pathogenesis and potential targeted therapies.

scholarly journals Molecular Pathogenesis of Pseudohypoaldosteronism Type II: Generation and Analysis of a Wnk4D561A/+ Knockin Mouse Model

2007 ◽  
Vol 5 (5) ◽  
pp. 331-344 ◽  
Author(s):  
Sung-Sen Yang ◽  
Tetsuji Morimoto ◽  
Tatemitsu Rai ◽  
Motoko Chiga ◽  
Eisei Sohara ◽  
...  
Keyword(s):  
Mouse Model ◽  
Molecular Pathogenesis ◽  
Type Ii ◽  
Pseudohypoaldosteronism Type Ii ◽  
Knockin Mouse ◽  
Pseudohypoaldosteronism Type

scholarly journals HYPERTENSION DOES NOT CONTRIBUTE TO MICROBLEEDS ONSET IN FEMALE EFAD MICE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S93-S93
Author(s):  
Mafalda Cacciottolo ◽  
Todd E Morgan ◽  
Caleb E Finch
Keyword(s):  
Blood Pressure ◽  
Alzheimer Disease ◽  
Mouse Model ◽  
Age Changes ◽  
Clinical Burden ◽  
Longitudinal Measurements ◽  
Age Related ◽  
Amyloid Deposits ◽  
Tail Cuff

Abstract Cerebral microbleeds (MBs) contribute to pre-clinical cognitive decline and are an additional clinical burden in Alzheimer Disease (AD). Hypertension is associated with MBs, with nearly 2-fold higher likelihood for MBs per SD increment in blood pressure (BP). We investigated the possible role of age-related hypertension in the EFAD mouse model (transgenic for carrying familial AD mutations and targeted replacement of human APO-E3 or -E4). MBs were detected by Prussian Blue histochemistry. We extended prior findings with observations that MBs arise early in life, by 2 months, and confirmed female excess for ApoE3 and-E4 carriers. Wildtype C57BL/6J mice also accumulated MBs, and a 10-fold lower level and more slowly up to 21mo of age. BP was measured by the tail-cuff method. All mice had BP in the normotensive range, <150 mm Hg, systolic. Longitudinal measurements of blood pressure at ages 2, 4, and 6 months showed few age changes, except for E3FAD females at 6 months (systolic, +20%, p<0.05; diastolic, +33%, p<0.05). A possible decrease in blood pressure was observed in EFAD mice (-33%, p<0.01) compared to C57BL/6J mice. A not statistical trend of increase was observed in older C57BL/6J mice up to 18 mo of age, consistent with previous reports. Older ages are required for complete negation of role of hypertension in the MB model. Ongoing studies will examine mice older than 6 months for potential relations of blood pressure and MB, and in relation to brain amyloid deposits which surrounded MBs in our prior study.

scholarly journals Role of blood pressure and the renin-angiotensin system in development of diabetic nephropathy (DN) in eNOS−/− db/db mice

2012 ◽  
Vol 302 (4) ◽  
pp. F433-F438 ◽  
Author(s):  
Ming-Zhi Zhang ◽  
Suwan Wang ◽  
Shilin Yang ◽  
Haichun Yang ◽  
Xiaofeng Fan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Diabetic Nephropathy ◽  
Triple Therapy ◽  
Type Ii Diabetes ◽  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Type Ii ◽  
Angiotensin System ◽  
Renin Angiotensin

Randomized clinical trials have clearly shown that inhibition of the renin-angiotensin system (RAS) will slow the rate of progression of diabetic nephropathy, but controversy remains about whether the observed beneficial effects result from more than control of blood pressure. Deletion of eNOS in a model of type II diabetes, db/db mice (eNOS−/− db/db), induces an accelerated nephropathy and provides an excellent model of human diabetic nephropathy. As is frequently seen in type II diabetes, blood pressure is moderately elevated in eNOS−/− db/db mice. To determine the role of elevated blood pressure per se vs. additional deleterious effects of the RAS in mediation of disease progression, 8-wk-old eNOS−/− db/db mice were randomly divided into three groups: vehicle, treatment with the angiotensin-converting enzyme inhibitor (ACEI) captopril, or treatment with “triple therapy” (hydralazine, resperine, hydrocholorothiazide), and the animals were euthanized after treatment for 12 wk. Blood pressure was reduced to comparable levels with ACE inhibition or triple therapy. Although both treatment regimens decreased development of diabetic nephropathy, ACE inhibition led to more profound reductions in albuminuria, glomerulosclerosis, markers of tubulointerstitial injury, macrophage infiltration, and markers of inflammation. Therefore, this animal model suggests that while there is an important role for blood pressure control, RAS blockade provides additional benefits in slowing the progression of diabetic nephropathy.

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