Vascular smooth muscle Gq signaling is involved in high blood pressure in both induced renal and genetic vascular smooth muscle-derived models of hypertension

2007 ◽  
Vol 293 (5) ◽  
pp. H3072-H3079 ◽  
Author(s):  
David M. Harris ◽  
Heather I. Cohn ◽  
Stéphanie Pesant ◽  
Rui-Hai Zhou ◽  
Andrea D. Eckhart
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Renal Artery ◽  
Renal Artery Stenosis ◽  
Antihypertensive Therapy ◽  
High Blood Pressure ◽  
Vascular Function ◽  
Artery Stenosis ◽  
Ang Ii

More than 30% of the US population has high blood pressure (BP), and less than a third of people treated for hypertension have it controlled. In addition, the etiology of most high BP is not known. Having a better understanding of the mechanisms underlying hypertension could potentially increase the effectiveness of treatment. Because Gq signaling mediates vasoconstriction and vascular function can cause BP abnormalities, we were interested in determining the role of vascular smooth muscle (VSM) Gq signaling in two divergent models of hypertension: a renovascular model of hypertension through renal artery stenosis and a genetic model of hypertension using mice with VSM-derived high BP. Inhibition of VSM Gq signaling attenuated BP increases induced by renal artery stenosis to a similar extent as losartan, an ANG II receptor blocker and current antihypertensive therapy. Inhibition of Gq signaling also attenuated high BP in our genetic VSM-derived hypertensive model. In contrast, BP remained elevated 25% following treatment with losartan, and prazosin, an α1-adrenergic receptor antagonist, only decreased BP by 35%. Inhibition of Gq signaling attenuated VSM reactivity to ANG II and resulted in a 2.4-fold rightward shift in EC50. We also determined that inhibition of Gq signaling was able to reverse VSM hypertrophy in the genetic VSM-derived hypertensive model. These results suggest that Gq signaling is an important signaling pathway in two divergent models of hypertension and, perhaps, optimization of antihypertensive therapy could occur with the identification of particular Gq-coupled receptors involved.

scholarly journals Clinical response scores to predict blood pressure and renal function improvement following renal artery stenting for atherosclerotic renal artery stenosis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Kablak-Ziembicka ◽  
A Roslawiecka ◽  
R Badacz ◽  
A Sokolowski ◽  
P Musialek ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Logistic Regression ◽  
Renal Function ◽  
Renal Artery ◽  
Renal Artery Stenosis ◽  
Predictive Models ◽  
Artery Stenosis ◽  
Atherosclerotic Renal Artery Stenosis ◽  
Baseline Serum ◽  
Kidney Length

Abstract Background It is little known about predictors of systolic (SBP) and diastolic (DBP) blood pressure or renal function (eGFR) improvement in patients with atherosclerotic renal artery stenosis (ARAS) undergoing stent-assisted angioplasty (PTA). Therefore, we aimed to build a prediction scores that would indicate characteristics of patient subsets with ARAS most likely to have clinical improvement following PTA. Methods 201 patients who underwent PTA for ARAS (2003–2018) were categorized as eGFR or SBP/DBP responders based on eGFR increase of ≥11 ml/min/1.73m2, decrease of SBP ≥20mmHg and DBP ≥5mmHg at 12-months following PTA. The remaining patients were classified as non-responders. The performance of logistic regression models were evaluated by basic decision characteristics. Continuous data have been transformed into binary coding with help of operating characteristic (ROC) curve. Predictive models have been constructed for each followed by construction of predictive models in each of 3 categories. Results Logistic regression analysis showed that: baseline SBP>145 mmHg, DBP >82 mmHg, previous myocardial infarction and Renal-Aotric-Ratio >5.1 were independent influencing factors of SBP response, with relative risk percentage shares of 69.8%; 12.1%; 10.9%; and 7.2%, respectively (sensitivity: 82%, specificity: 86.3%, positive (PPV):82% and negative (NPV) predictive values: 86.3%). The DBP decrease prediction model included baseline SBP >145 mmHg and DBP >82 mmHg, the ARAS progression, index kidney length >106 mm, and bilateral PTA with respective shares of 35.0%; 21.8%; 18.2%; 13.3% and 11.8%. (sensitivity: 76%, specificity: 77.8%, PPV: 80.7% and NPV: 72.6%). The eGFR increase was associated with baseline serum creatinine >122 μmol/L but eGFR greater than 30 ml/min/1.73m2, index kidney length >98 mm, end-diastolic velocity in index renal artery, renal resistive index <0.74, and requirement for >3 BP medications, with respective shares of 24.4%; 24.4%; 21.2%; 15% and 15% (sensitivity: 33.3%, specificity: 93.5%, PPV: 65.6% and NPV: 78.9%). Conclusions Current study identified clinical characteristics of patients who most likely to respond to PTA for ARAS. The sutability of the score should be verified in a prospective cohort of patients referred to PTA of ARAS Funding Acknowledgement Type of funding source: None

MO233RENAL ARTERY STENOSIS: DO NOT FORGET INHERITED THROMBOPHILIA

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Marwa Omrane ◽  
Yosra Ben Ariba ◽  
Imen Ouertani ◽  
Jannet Labidi
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Renal Artery ◽  
High Blood Pressure ◽  
Protein C ◽  
Artery Bypass ◽  
Duplex Ultrasound ◽  
Protein S ◽  
Artery Stenosis ◽  
Inherited Thrombophilia

Abstract Background and Aims Inherited thrombophilia can be defined as a genetically determined predisposition to develop thromboembolic complications. Inherited prothrombotic risk factors include antithrombin deficiency, protein C and protein S deficiencies, activated protein C resistance due to Leiden factor V mutation, inherited hyperhomocysteinemia, prothrombin G20210A variant, dysfibrinogenemia and elevated factor VIII levels. Method We report the case of a patient with history of bilateral renal artery stenosis who presented with renal artery bypass thrombosis related to an inherited thrombophilia. Results We report a case of 40-year-old male patient who presented with extremely high blood pressure and hypokalemia without other biological abnormalities. The duplex ultrasound showed bilateral renal stenosis with chronic occlusion of the right renal artery and a tight stenosis of the left renal artery estimated at 50%. Renal angiography confirmed the bilateral stenosis, associated to a small right kidney. Renal scintigraphy with DMSA showed normal left renal function and right renal function estimated at 2%. The therapeutic decision was to perform an aorto-renal bypass surgery by the saphenous vein.After renal artery bypass the blood pressure improved markedly, maintaining this result at 12 months follow-up at clinical examination and duplex ultrasound. One year later, the patient presented with high blood pressure. The duplex ultrasound showed a stenosis of the bypass with a double stenosis of the left aorto renal bypass on renal angioscanner. The patient underwent angioplasty of the venous bridge with implantation of 2 stents with improvement of blood pressure after angioplasty. Six months later, the patient presented an unbalanced blood pressure, the ultrasound control with a vascular Doppler showed a stenosis at the stent. The antihypertensive treatment was increased, a thrombophilia balance was requested concluding a combined protein C and protein S deficiency. Conclusion An etiological assessment should be carried out systematically in the event of thrombosis occurring before the age of 40 or in the case of iterative venous or arterial thrombosis. A genetic study where appropriate and a family screening are then recommended.

scholarly journals Angiotensin II, Hypercholesterolemia, and Vascular Smooth Muscle Cells: A Perfect Trio for Vascular Pathology

2020 ◽  
Vol 21 (12) ◽  
pp. 4525
Author(s):  
Amanda St. Paul ◽  
Cali B. Corbett ◽  
Rachael Okune ◽  
Michael V. Autieri
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Vascular Diseases ◽  
Reduce Blood Pressure ◽  
Vascular Pathology ◽  
Lipid Lowering ◽  
Ang Ii

Cardiovascular disease is the leading cause of morbidity and mortality in the Western and developing world, and the incidence of cardiovascular disease is increasing with the longer lifespan afforded by our modern lifestyle. Vascular diseases including coronary heart disease, high blood pressure, and stroke comprise the majority of cardiovascular diseases, and therefore represent a significant medical and socioeconomic burden on our society. It may not be surprising that these conditions overlap and potentiate each other when we consider the many cellular and molecular similarities between them. These intersecting points are manifested in clinical studies in which lipid lowering therapies reduce blood pressure, and anti-hypertensive medications reduce atherosclerotic plaque. At the molecular level, the vascular smooth muscle cell (VSMC) is the target, integrator, and effector cell of both atherogenic and the major effector protein of the hypertensive signal Angiotensin II (Ang II). Together, these signals can potentiate each other and prime the artery and exacerbate hypertension and atherosclerosis. Therefore, VSMCs are the fulcrum in progression of these diseases and, therefore, understanding the effects of atherogenic stimuli and Ang II on the VSMC is key to understanding and treating atherosclerosis and hypertension. In this review, we will examine studies in which hypertension and atherosclerosis intersect on the VSMC, and illustrate common pathways between these two diseases and vascular aging.

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