Abstract P018: The Angiotensin Type 2 Receptor (AT 2 R) Is Involved In The Etiology Of Inverse Salt Sensitivity Of Blood Pressure

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Peng Xu ◽  
Kwabena Sarpong ◽  
John J Gildea ◽  
Stephen Marshall ◽  
Wei Yue ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Plasma Membrane ◽  
Salt Sensitivity ◽  
T Test ◽  
Elevated Blood Pressure ◽  
Sodium Reabsorption ◽  
Elevated Blood ◽  
Salt Diet ◽  
Angiotensin Type 2 Receptor

Renal proximal tubule (RPT) dopamine D 1 -like receptors (D 1 R) and angiotensin II type-2 receptor (AT 2 R) inhibit sodium reabsorption and counter regulate the renin angiotensin systems AT 1 R which stimulates sodium reabsorption. Salt sensitivity of blood pressure (SS) is defined as a ≥7-mmHg rise in blood pressure following a week of daily consumption of 350 mM sodium chloride (NaCl). Inverse salt sensitivity (ISS) is defined as a ≥7-mm Hg increase in blood pressure (BP) after a week of 10 mM NaCl/day. Salt resistant controls were defined as < 7mM Hg change in BP whether on 10 or 350mmHg NaCl/day for one week. Previously, we demonstrated that D 1 R RPT membrane recruitment was inversely proportional to an individual’s degree of BP increase on a 350 mM diet. We hypothesize that the degree of salt sensitivity of blood pressure would be inversely correlated with the recruitment of the AT 2 R to the plasma membrane induced by NaCl. Immunostaining shows that D 1 R was distributed in a fine granular manner throughout the whole plasma membrane, while AT 2 R shows a punctate pattern in both urine-derived SR and ISS RPTCs. There was no difference of basal D 1 R or AT 2 R expression. Increasing cell NaCl (monensin ionophore 10 μM, 1 hour) resulted in a significantly more AT 2 R and D 1 R(control) recruitment to cell surface in ISS cells than in SR cells (D 1 R: MON/VEH: SR, 1.032 ± 0.056, n=4; ISS, 1.537 ± 0.097, n=4; t-test, p<0.01; AT 2 R :MON/VEH: SR, 0.923 ± 0.063, n=3; ISS, 1.28 ± 0.106, n=3; t-test, p<0.05). Because ISS individuals present to the medical system with elevated blood pressure while on a low salt diet, they are often misdiagnosed as hypertensive. As our studies were conducted on RPT cells isolated from individual's urine, the D 1 R and AT 2 R response may contribute to the diagnosis of ISS individuals with elevated blood pressure while on a 10 mM salt diet, and provide better understanding on the etiology of ISS.

scholarly journals Elevated blood pressure in normotensive rats produced by ‘knockdown’ of the angiotensin type 2 receptor

2004 ◽  
Vol 89 (3) ◽  
pp. 313-322 ◽  
Author(s):  
HongWei Wang ◽  
Stefan Gallinat ◽  
Hong-wei Li ◽  
Colin Sumners ◽  
Mohan K. Raizada ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Angiotensin Type 2 Receptor ◽  
Angiotensin Type

Abstract 495: A Novel Test for Low Salt Sensitivity: Angiotensin type-II Receptor Recruitment After Dopamine-1 Receptor Stimulation in Urine-Derived Renal Proximal Tubule Cells

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
John J Gildea ◽  
Staci A Keene ◽  
Dylan T Lahiff ◽  
Robert E Van Sciver ◽  
Cynthia D Schoeffel ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Flow Cytometry ◽  
Clinical Study ◽  
Salt Sensitivity ◽  
High Salt ◽  
Salt Diet ◽  
Independent Events ◽  
Angiotensin Type 2 Receptor ◽  
Low Salt ◽  
Angiotensin Type

Salt-sensitivity of blood pressure is an inappropriate increase in blood pressure following high salt intake. Subjects in our clinical study were typed according to their salt-sensitivity status into 3 categories: High-Salt-Sensitive (HSS; ≥ 7 mmHg increase in mean arterial pressure (MAP) on a high salt diet of 300 mEq of sodium, 17% prevalence), Low-Salt-Sensitive (LSS:, who paradoxically showed a ≥ 7 mmHg increase in MAP on a low salt diet of 10 mEq of sodium, 11% prevalence), and Salt-Resistant (SR, individuals who showed no significant increase in blood pressure on either diet, 72% prevalence). We previously demonstrated that LSS subjects show increased recruitment of the natriuretic dopamine-1 receptor (D1R) to the plasma membrane following a salt stimulation as compared to HSS subjects. Stimulation of the D1R in RPTC with fenoldopam (dopaminergic agonist) results in recruitment of the natriuretic angiotensin type-2 receptor (AT2R) to the cell surface. We hypothesized that LSS individuals may also demonstrate an enhanced AT2R RPTC membrane recruitment compared to HSS individuals when challenged with fenoldopam. In order to gain access to fresh RPTC from each subject, we isolated exfoliated RPTC from randomly voided urine from SR, LSS, and HSS subjects from our clinical study. We measured three subjects from each category with a minimum of three voids for each subject. We counted individual cells as independent events using both the confocal microscope (n=245) and the flow cytometer (n=5344). We found an inverse correlation between AT2R recruitment and the degree of salt-sensitivity of blood pressure. Fenoldopam stimulated AT2R recruitment as measured by confocal microscopy (y = -0.0047x + 0.4966, R2 = 0.2488, P<0.0001) and flow cytometry (y =-0.057x + 1.5645, R2=0.2912, P=0.0185). Flow cytometry provided a more sensitive diagnostic for LSS than HSS subjects. AT2R recruitment was more predictive of LSS than HSS. AT2R recruitment may be used as a rapid method to test for LSS individuals who need to be identified and encouraged to increase their sodium intake in order to avoid paradoxical hypertension.

scholarly journals ‘Low-Salt’ Bread as an Important Component of a Pragmatic Reduced-Salt Diet for Lowering Blood Pressure in Adults with Elevated Blood Pressure

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1725 ◽  
Author(s):  
Kevin D. Cashman ◽  
Sorcha Kenny ◽  
Joseph P. Kerry ◽  
Fanny Leenhardt ◽  
Elke K. Arendt
Keyword(s):  
Blood Pressure ◽  
Bone Metabolism ◽  
Plasma Lipids ◽  
Salt Intake ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Salt Diet ◽  
Low Salt ◽  
Dietary Period ◽  
Reduced Salt

Reformulation of bread in terms of salt content remains an important measure to help achieve a reduction in salt intake in the population and for the prevention of hypertension and elevated blood pressure (BP). Our fundamental studies on the reduction of salt on dough and bread characteristics showed that wheat breads produced with 0.3 g salt/100 g (“low-salt”) were found to be comparable quality to that produced with the typical level of salt (1.2%). This food-based intervention trial examined, using a 5 week cross-over design, the potential for inclusion of “low-salt” bread as part of a pragmatic reduced-salt diet on BP, markers of bone metabolism, and plasma lipids in 97 adults with slightly to moderately elevated BP. Assuming all sodium from dietary intake was excreted through the urine, the intake of salt decreased by 1.7 g/day, on average, during the reduced-salt dietary period. Systolic BP was significantly lower (by 3.3 mmHg on average; p < 0.0001) during the reduced-salt dietary period compared to the usual-salt dietary period, but there was no significant difference (p = 0.81) in diastolic BP. There were no significant differences (p > 0.12, in all cases) in any of the urinary- or serum-based biochemical indices of calcium or bone metabolism or in plasma lipids between the two periods. In conclusion, a modest reduction in dietary salt intake, in which the use of “low-salt” (i.e., 0.3 g/100g) bread played a key role along with dietary advice, and led to a significant, and clinically meaningful, decrease in systolic, but not diastolic, BP in adults with mildly to moderately elevated BP.

scholarly journals The significance of some anthropometric parameters and parameters ensuing from them in assessing cardiovascular risk in type 2 diabetes

2006 ◽  
Vol 59 (1-2) ◽  
pp. 67-71
Author(s):  
Aniko Katona-Djurekovic ◽  
Edita Stokic
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Risk ◽  
Hdl Cholesterol ◽  
Elevated Blood Pressure ◽  
Diabetic Patients ◽  
Elevated Blood ◽  
Anthropometric Parameters ◽  
Type 2 Diabetics ◽  
Conicity Index

Introduction. Current clinical practice requires simple and available tools for cardiovascular risk assessment in diabetic patients. Material and methods. This study included 290 type 2 diabetics of both sexes. The following anthropometric parameters were measured: body mass index, waist circumference, sagital abdominal diameter, while ensuing parameters included: waist-to-stature ratio(WSH), ratio of abdominal sagital diameter to height (SADE), and conicity index. Metabolic status was evaluated based on lipidograms and HbAlc, and of cardiovascular parameters blood pressure was measured. Results. Female patients were obese, with central accumulation of fat, elevated blood pressure and lipid disorders such as hypo-HDL cholesterolemia. The applied anthropometric parameters and indicators ensuing from them (WSH, SADH and conicity index), are reliable indicators of elevated blood pressure in diabetic patients. Conclusion. The obtained results showed negative correlation with HDL cholesterol in women, which indirectly indicates to development of hypertension, as one of the most common diabetic complications. Central accumulation of fat with dyslipidemic disorder, characteristic of metabolic syndrome, is of highest importance. Sagital abdominal diameter (SAD) and WSH showed the highest correlation with lipidograms in females, whereas BMI was the best indicator in males. .

Fructose-rich diet differently affects angiotensin II receptor content in the nucleus and a plasma membrane fraction of visceral adipose tissue

2017 ◽  
Vol 42 (12) ◽  
pp. 1254-1263 ◽  
Author(s):  
Maja Bundalo ◽  
Ana Djordjevic ◽  
Biljana Bursac ◽  
Maja Zivkovic ◽  
Goran Koricanac ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adipose Tissue ◽  
Plasma Membrane ◽  
Visceral Adipose Tissue ◽  
Elevated Blood Pressure ◽  
Angiotensin Receptors ◽  
Nuclear Fraction ◽  
Mrna Levels ◽  
Elevated Blood ◽  
Visceral Adipose

The adipose tissue renin–angiotensin system (RAS) is proposed to be a pathophysiological link between adipose tissue dysregulation and metabolic disorders induced by a fructose-rich diet (FRD). RAS can act intracellularly. We hypothesized that adipocyte nuclear membranes possess angiotensin receptor types 1 and 2 (AT1R and AT2R), which couple to nuclear signaling pathways and regulate oxidative gene expression under FRD conditions. We analyzed the effect of consumption of 10% fructose solution for 9 weeks on biochemical parameters, adipocyte morphology, and expression of AT1R, AT2R, AT1R-associated protein (ATRAP), NADPH oxidase 4 (NOX4), matrix metalloproteinase-9 (MMP-9), and manganese superoxide dismutase (MnSOD) in adipose tissue of Wistar rats. We detected AT1R and AT2R in the nuclear fraction. FRD reduced the level of angiotensin receptors in the nucleus, while increased AT1R and decreased AT2R levels were observed in the plasma membrane. FRD increased the ATRAP mRNA level and decreased MnSOD mRNA and protein levels. No significant differences were observed for MMP-9 and NOX4 mRNA levels. These findings coincided with hyperleptinemia, elevated blood pressure and triglycerides, and unchanged visceral adipose tissue mass and morphology in FRD rats. Besides providing evidence for nuclear localization of angiotensin receptors in visceral adipose tissue, this study demonstrates the different effects of FRD on AT1R expression in different cellular compartments. Elevated blood pressure and decreased antioxidant capacity in visceral fat of fructose-fed rats were accompanied by an increased AT1R level in the plasma membrane, while upregulation of ATRAP and a decrease of nuclear membrane AT1R suggest an increased capacity for attenuation of excessive AT1R signaling and visceral adiposity.

scholarly journals Association of Alcohol Intake With Hypertension in Type 2 Diabetes Mellitus: The ACCORD Trial

2020 ◽  
Vol 9 (18) ◽  
Author(s):  
Jonathan J. Mayl ◽  
Charles A. German ◽  
Alain G. Bertoni ◽  
Bharathi Upadhya ◽  
Prashant D. Bhave ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Alcohol Consumption ◽  
Elevated Blood Pressure ◽  
Moderate Alcohol Consumption ◽  
Elevated Blood ◽  
Pressure Stage ◽  
Heavy Alcohol Consumption ◽  
Stage 1

Background Heavy alcohol consumption has a well‐established association with hypertension. However, doubt persists whether moderate alcohol consumption has a similar link. This relationship is not well‐studied in patients with diabetes mellitus. We aimed to describe the association of alcohol consumption with prevalent hypertension in participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial. Methods and Results Alcohol consumption was categorized as none, light (1–7 drinks/week), moderate (8–14 drinks/week), and heavy (≥15 drinks/week). Blood pressure was categorized using American College of Cardiology/American Heart Association guidelines as normal, elevated blood pressure, stage 1 hypertension, and stage 2 hypertension. Multivariable logistic regression was used to explore the association between alcohol consumption and prevalent hypertension. A total of 10 200 eligible participants were analyzed. Light alcohol consumption was not associated with elevated blood pressure or any stage hypertension. Moderate alcohol consumption was associated with elevated blood pressure, stage 1, and stage 2 hypertension (odds ratio [OR], 1.79; 95% CI, 1.04–3.11, P =0.03; OR, 1.66; 95% CI, 1.05–2.60, P =0.03; and OR, 1.62; 95% CI, 1.03–2.54, P =0.03, respectively). Heavy alcohol consumption was associated with elevated blood pressure, stage 1, and stage 2 hypertension (OR, 1.91; 95% CI, 1.17–3.12, P =0.01; OR, 2.49; 95% CI, 1.03–6.17, P =0.03; and OR, 3.04; 95% CI, 1.28–7.22, P =0.01, respectively). Conclusions Despite prior research, our findings show moderate alcohol consumption is associated with hypertension in patients with type 2 diabetes mellitus and elevated cardiovascular risk. We also note a dose‐risk relationship with the amount of alcohol consumed and the degree of hypertension.

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