scholarly journals Mas Receptor Activation Contributes to the Improvement of Nitric Oxide Bioavailability and Vascular Remodeling During Chronic AT1R (Angiotensin Type-1 Receptor) Blockade in Experimental Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (6) ◽  
pp. 1753-1761
Author(s):  
Carmine Savoia ◽  
Emanuele Arrabito ◽  
Rosa Parente ◽  
Carmine Nicoletti ◽  
Luca Madaro ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Pressure Control ◽  
Pressure Control ◽  
Favorable Effect ◽  
Receptor Blockade ◽  
No Bioavailability ◽  
And Function ◽  
Angiotensin Type

Angiotensin (1–7) production increases during AT1R (angiotensin type-1 receptor) blockade. The contribution of Ang (1–7) (angiotensin [1–7]) and its receptor (MasR) to the favorable effect of angiotensin receptor blockers on remodeling and function of resistance arteries remains unclear. We sought to determine whether MasR contributes to the improvement of vascular structure and function during chronic AT1R blockade. Spontaneously hypertensive rats were treated with Ang (1–7) or olmesartan ± MasR antagonist A-779, or vehicle, for 14 days. Blood pressure was measured by tail cuff methodology. Mesenteric arteries were dissected and mounted on a pressurized micromyograph to evaluate media-to-lumen ratio (M/L) and endothelial function. Expression of MasR and eNOS (endothelial nitric oxide synthase) was evaluated by immunoblotting, plasma nitrate by colorimetric assay, and reactive oxygen species production by dihydroethidium staining. Independently of blood pressure, olmesartan significantly reduced M/L and improved NO bioavailability, A-779 prevented these effects. Likewise, Ang (1–7) significantly reduced M/L and NO bioavailability. MasR expression was significantly increased by Ang (1–7) as well as by olmesartan, and it was blunted in the presence of A-779. Both Ang (1–7) and olmesartan increased eNOS expression and plasma nitrite which were reduced by A-779. Superoxide generation was attenuated by olmesartan and Ang (1–7) and was blunted in the presence of A-779. These MasR-mediated actions were independent of AT2R activation since olmesartan and Ang (1–7) increased MasR expression and reduced M/L in Ang II (angiotensin II)–infused AT2R knockout mice, independently of blood pressure control. A-779 prevented these effects. Hence, MasR activation may contribute to the favorable effects of AT1R antagonism on NO bioavailability and microvascular remodeling, independently of AT2R activation and blood pressure control.

Nitric oxide: Its identity and role in blood pressure control

Life Sciences ◽  
1995 ◽  
Vol 57 (17) ◽  
pp. 1547-1556 ◽  
Author(s):  
Shyamal Das ◽  
Keshava N. Kumar
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Pressure Control ◽  
Pressure Control

Joint testing of overall and simple effects for the two-by-two factorial trial design

2021 ◽  
Vol 18 (5) ◽  
pp. 521-528
Author(s):  
Eric S Leifer ◽  
James F Troendle ◽  
Alexis Kolecki ◽  
Dean A Follmann
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Control ◽  
Multiple Testing ◽  
Pressure Control ◽  
Factorial Analysis ◽  
Testing Procedures ◽  
Type 1 Error ◽  
Multiple Testing Procedures ◽  
To Receive

Background/aims: The two-by-two factorial design randomizes participants to receive treatment A alone, treatment B alone, both treatments A and B( AB), or neither treatment ( C). When the combined effect of A and B is less than the sum of the A and B effects, called a subadditive interaction, there can be low power to detect the A effect using an overall test, that is, factorial analysis, which compares the A and AB groups to the C and B groups. Such an interaction may have occurred in the Action to Control Cardiovascular Risk in Diabetes blood pressure trial (ACCORD BP) which simultaneously randomized participants to receive intensive or standard blood pressure, control and intensive or standard glycemic control. For the primary outcome of major cardiovascular event, the overall test for efficacy of intensive blood pressure control was nonsignificant. In such an instance, simple effect tests of A versus C and B versus C may be useful since they are not affected by a subadditive interaction, but they can have lower power since they use half the participants of the overall trial. We investigate multiple testing procedures which exploit the overall tests’ sample size advantage and the simple tests’ robustness to a potential interaction. Methods: In the time-to-event setting, we use the stratified and ordinary logrank statistics’ asymptotic means to calculate the power of the overall and simple tests under various scenarios. We consider the A and B research questions to be unrelated and allocate 0.05 significance level to each. For each question, we investigate three multiple testing procedures which allocate the type 1 error in different proportions for the overall and simple effects as well as the AB effect. The Equal Allocation 3 procedure allocates equal type 1 error to each of the three effects, the Proportional Allocation 2 procedure allocates 2/3 of the type 1 error to the overall A (respectively, B) effect and the remaining type 1 error to the AB effect, and the Equal Allocation 2 procedure allocates equal amounts to the simple A (respectively, B) and AB effects. These procedures are applied to ACCORD BP. Results: Across various scenarios, Equal Allocation 3 had robust power for detecting a true effect. For ACCORD BP, all three procedures would have detected a benefit of intensive glycemia control. Conclusions: When there is no interaction, Equal Allocation 3 has less power than a factorial analysis. However, Equal Allocation 3 often has greater power when there is an interaction. The R package factorial2x2 can be used to explore the power gain or loss for different scenarios.

Autonomic blood pressure control in children and adolescents with type 1 diabetes mellitus

2009 ◽  
Vol 10 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Margit Krause ◽  
Heinz Rüdiger ◽  
Martin Bald ◽  
Andrea Näke ◽  
Ekkehart Paditz
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Children And Adolescents ◽  
Blood Pressure Control ◽  
Pressure Control

Diabetes mellitus and the kidney

2020 ◽  
pp. 4975-4987
Author(s):  
Rudolf Bilous
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Glomerular Filtration Rate ◽  
Glycaemic Control ◽  
Blood Pressure Control ◽  
Ace Inhibitors ◽  
Filtration Rate ◽  
Pressure Control

Diabetic nephropathy is the commonest cause of endstage renal disease in the developed world. Aetiology and pathology—causation is related to glycaemic control, hypertension, inflammation, genetic factors, and dietary and other environmental factors. Pathological hallmarks in the glomerulus are thickening of the glomerular basement membrane and mesangial expansion, with or without nodule formation, secondary to an accumulation of extracellular matrix. Many patients have a varying severity of tubulointerstitial inflammation and fibrosis. Staging and natural history—is classically described in terms of urinary albumin excretion rate (UAER). Clinical features—most patients (>60%) will have a normal UAER throughout their diabetic life, but 1 to 2% of the remainder develop persistent moderately increased albuminuria each year. Once UAER exceeds 200 µg/min, there tends to be a relentless increase in proteinuria and glomerular filtration rate declines progressively at a rate that largely depends upon blood pressure control. Prevention—tight glycaemic control can prevent moderately increased albuminuria in both type 1 and type 2 diabetes. Whether intensive blood pressure control using angiotensin-converting enzyme (ACE) inhibitors can also prevent this remains controversial. In both type 1 and type 2 diabetes, intensive blood pressure control using ACE inhibitors or angiotensin II receptor blockers (ARBs) slows progression from moderately to severely increased albuminuria and also slows the rate of decline in glomerular filtration rate in those with severely increased albuminuria. Management—aims for (1) control of glycaemia, (2) control of hypertension (<130/80 mmHg) using an ACE inhibitor or an ARB as first line; and (3) other interventions, including some or all of serum lipid lowering, smoking cessation, and reduction of dietary protein and salt.

Does nitric oxide synthesis really contribute to systemic blood pressure control?

1995 ◽  
Vol 13 (6) ◽  
pp. 709 ◽  
Author(s):  
Marielle M. E. Krekels ◽  
Frank C. Huvers ◽  
Peter W. de Leeuw ◽  
Nicolaas C. Schaper
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Pressure Control ◽  
Pressure Control ◽  
Systemic Blood Pressure ◽  
Nitric Oxide Synthesis ◽  
Systemic Blood
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