Angiotensin-(3–4) (Val-Tyr) Normalizes the Elevated Arterial Blood Pressure and Abnormal Na+/Energy Handling Associated With Chronic Undernutrition by Counteracting the Effects Mediated by Type 1 Angiotensin II Receptors

2021 ◽  
Author(s):  
Amaury Pereira-Acacio ◽  
João Veloso-Santos ◽  
Luiz Nossar ◽  
Gloria Costa-Sarmento ◽  
Humberto Muzi-Filho ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Proximal Tubule ◽  
Energy Intake ◽  
Chronic Administration ◽  
Poor Quality ◽  
Vitamin Supplementation ◽  
High Systolic Blood Pressure ◽  
Proximal Tubule Cells ◽  
Arterial Blood ◽  
Control Body

Abstract Purpose To investigate the mechanisms by which chronic administration of a multideficient diet after weaning alters bodily Na+ handling, and culminates in high systolic blood pressure (SBP) at a juvenile age.Methods From 28 to 93 days of age, weaned male Wistar rats were given a diet with low content and poor-quality protein, low lipid, without vitamin supplementation, which mimics the diets consumed in impoverished regions worldwide. We measured food, energy and Na+ ingestion, together with urinary Na+ excretion, Na+ density (Na+ intake/energy intake), plasma Na+ concentration, SBP), and renal proximal tubule Na+-transporting ATPases. Results Undernourished rats aged 93 days had only one-third of the control body mass, lower plasma albumin, higher SBP, higher energy intake, and higher positive Na+ balance accompanied by decreased plasma Na+ concentration. SBP was normalized with Losartan and with Ang-(3–4), and the combination of the 2 substances induced an accentuated negative Na+ balance as a result of strong inhibition of Na+ ingestion. Na+ density in undernourished rats was higher than in control, irrespective of the treatment, and they had downregulated (Na++K+)ATPase and upregulated Na+-ATPase in proximal tubule cells, which returned to control levels after Losartan or Ang-(3–4).Conclusions Na+ density, not only Na+ ingestion, plays a central role in the pathophysiology of elevated SBP in chronically undernourished rats. The observations that Losartan and Ang-(3–4) normalized SBP together with Na+ distribution and handling give support to the proposal that Ang IIÞAT1R and Ang IIÞAT2R axes have opposite roles within the renin-angiotensin-aldosterone system of undernourished juvenile rats.

Abstract 065: Overexpression of an Intracellular Angiotensin II Fusion Protein Selectively in the Mitochondria of the Proximal Tubules Elevates Blood Pressure in Mice via AT 1a Receptor-mediated Mitochondrial Respiratory and Glycolysis Stress

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Xiao C Li ◽  
Manoocher Soleimani ◽  
Hoang Nguyen ◽  
Hong Li ◽  
Jia L Zhuo
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Fusion Protein ◽  
Proximal Tubule ◽  
Physiological Role ◽  
Proximal Tubules ◽  
Ang Ii ◽  
Stress Tests ◽  
Arterial Blood ◽  
Mitochondrial Respiratory

An intracrine mitochondrial renin-angiotensin system (RAS) has recently been identified in various animal and human tissues, but whether the mitochondrial RAS plays a physiological role in the regulation of blood pressure remains unknown. The present study tested whether overexpression of an intracellular angiotensin II fusion protein, ECFP/ANG II, selectively in the mitochondria of the proximal tubules alters blood pressure, and whether the effects may involve AT 1a receptors and the Na + /H + exchanger 3 (NHE3). An adenoviral vector encoding ECFP/ANG II, a mitochondria targeting sequence, and the sglt2 promoter, Ad-sglt2-mito-ECFP/ANG II, was constructed for proximal tubule- and mitochondria-specific overexpression for 2 weeks. In adult male C57BL/6J mice, overexpression of mito-ECFP/ANG II in the mitochondria of the proximal tubules increased systolic blood pressure (SBP) significantly (Control: 116 ± 3 vs. mito-ECFP/ANG II: 128 ± 3 mmHg; p <0.01, n=15). The blood pressure-increasing effect of Ad-sglt2-mito-ECFP/ANG II was blocked in proximal tubule-specific AT 1a -KO mice (Control: 105 ± 2 vs. mito-ECFP/ANG II: 104 ± 4 mmHg; n.s ., n=7), or in proximal tubule-specific NHE3-KO mice (Control: 108 ± 3 vs. mito-ECFP/ANG II: 107 ± 3 mmHg; n.s ., n=13), respectively. In further experiments, mouse proximal tubule cells were transfected with Ad-sglt2-mito-ECFP/ANG II for 48 h and treated with the AT 1 blocker losartan (10 μM) or the AT 2 blocker PD123319 (10 μM) to measure mitochondrial respiratory and glycolytic function using Seahorse XF Cell Mito and XF Glycolysis Stress Tests. The mito-ECFP/ANG II expression was robust and colocalized with MitoTracker® Red FM. Overexpression of mito-ECFP/ANG II markedly increased oxygen consumption rate (OCR) (Control: 139.4 ± 9.2 vs. mito-ECFP/ANG II: 236.3 ± 12.6 pmol/min; p <0.01, n=12) and extracellular acidification rate (ECAR) (Control: 8.8 ± 0.6 vs. mito-ECFP/ANG II: 11.8 ± 1.2 mpH/min; p <0.01, n=12), respectively. Losartan blocked the effects of mito-ECFP/ANG II on OCR and ECAR, whereas PD123319 had no effect. We conclude that intracellular ANG II may activate AT 1 receptors in the mitochondria of the proximal tubules to alter mitochondrial respiratory and glycolytic function and arterial blood pressure.

Abstract 79: Caveolin-1 Knockout Mice Have Salt-Sensitive Hypertension and Dopamine-1 Receptor Defects in Renal Cortex and Isolated Renal Proximal Tubule Cells

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
John J Gildea ◽  
Nancy L Howell ◽  
Robert E Van Sciver ◽  
Brandon A Kemp ◽  
Robert M Carey ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Proximal Tubule ◽  
Kinase Activity ◽  
Renal Cortex ◽  
Renal Proximal Tubule ◽  
Normal Blood Pressure ◽  
Proximal Tubule Cells ◽  
Caveolin 1 ◽  
Tubule Cells ◽  
Renal Proximal Tubule Cells

Dopamine-1 receptors (D1R) are necessary for kidney proximal tubule-dependent natriuresis and maintenance of normal blood pressure, especially under high salt conditions. G-protein coupled receptor kinase 4 (GRK4) is a negative regulator of D1R function and single nucleotide polymorphisms in GRK4 have been associated with both hypertension and salt sensitivity in humans. Caveolin-1 (CAV1) directly binds to GRK4 and decreases kinase activity. We hypothesized that CAV1 knockout mice (CAV1KO) would have increased GRK4 kinase activity due to lack of physical interaction and inhibition of GRK4; thus overactive GRK4 would inactivate the D1R. Mean arterial blood pressure (MAP, in mmHg ±SEM) measured over 5 days was not significantly different for Wild-type mice (WT, 128.9±4.2 mmHg, n=4) vs CAV1KO (129.5±3.5 mmHg, n=4) on normal chow (0.3% sodium). However, on a 4% high sodium diet, the MAP of CAV1KO mice increased in just 2 days by 20.1±4.2 mmHg (p<0.05 vs either Day 0 CAV1KO or Day 2 WT, n=4). The CAV1KO MAP increased by 25.9±6.6 mmHg by day 7 (p<0.05 vs either Day 0 CAV1KO or Day 7 WT, n=4). Hyperphosphorylation and inactivation of the D1R in renal cortex was examined by looking at phospho-serine D1R by immuno-precipitation and Western dot blotting. A 92.5% ± 18.8 SEM increase in phospho-D1R was found in the CAV1KO renal cortex (n=4, p<0.01 vs WT; 14,574/7570 RFU). Cortical slices were made and incubated for 30 minutes with fenoldopam (FEN, 10 μM) with or without LE300 (D1R-like antagonist, 10 μM) or vehicle (VEH). Cyclic AMP was measured by TR-FRET (Lance, Perkin Elmer). FEN significantly increased cAMP 5.6 fold ± 1.2 SEM (n=4, p<0.01 vs VEH; 7.84/1.4 pmole/mg protein) in WT but not in CAV1KO slices, and this effect was completely blocked by LE300. Primary mouse CAV1KO and WT renal proximal tubule cell lines were established and monensin (sodium ionophore, 5 μM, 30 minutes)-induced plasma membrane D1R recruitment increased as measured by confocal microscopy in WT (30.4% ± 7.4 SEM, n=11, p<0.01 vs VEH; 8990/6894 RFU) but not in CAV1KO proximal tubule cells. In summary, CAV1 is necessary in high salt conditions for maintaining normal blood pressure in mice and for preserving normal D1R function in kidney cortex and in mouse renal proximal tubule cells.

Acute hypotension induced by aortic clamp vs. PTH provokes distinct proximal tubule Na+ transporter redistribution patterns

2004 ◽  
Vol 287 (4) ◽  
pp. R878-R885 ◽  
Author(s):  
Patrick K. K. Leong ◽  
Li E. Yang ◽  
Harrison W. Lin ◽  
Niels H. Holstein-Rathlou ◽  
Alicia A. McDonough
Keyword(s):  
Blood Pressure ◽  
Proximal Tubule ◽  
Subcellular Distribution ◽  
Urine Output ◽  
Volume Flow ◽  
High Dose ◽  
Arterial Blood ◽  
Acute Hypotension ◽  
High Doses ◽  
Cortical Membranes

Renal parathyroid hormone (PTH) action is often studied at high doses (100 μg PTH/kg) that lower mean arterial pressure significantly, albeit transiently, complicating interpretation of studies. Little is known about the effect of acute hypotension on proximal tubule Na+ transporters. This study aimed to determine the effects of acute hypotension, induced by aortic clamp or by high-dose PTH (100 μg PTH/kg), on renal hemodynamics and proximal tubule Na/H exchanger isoform 3 (NHE3) and type IIa Na-Pi cotransporter protein (NaPi2) distribution. Subcellular distribution was analyzed in renal cortical membranes fractionated on sorbitol density gradients. Aortic clamp-induced acute hypotension (from 100 ± 3 to 78 ± 2 mmHg) provoked a 62% decrease in urine output and a significant decrease in volume flow from the proximal tubule detected as a 66% decrease in endogenous lithium clearance. There was, however, no significant change in glomerular filtration rate (GFR) or subcellular distribution of NHE3 and NaPi2. In contrast, high-dose PTH rapidly (<2 min) decreased arterial blood pressure to 51 ± 3 mmHg, decreased urine output, and shifted NHE3 and NaPi2 out of the low-density membranes enriched in apical markers. PTH at much lower doses (<1.4 μg·kg−1·h−1) did not change blood pressure and was diuretic. In conclusion, acute hypotension per se increases proximal tubule Na+ reabsorption without changing NHE3 or NaPi2 subcellular distribution, indicating that trafficking of transporters to the surface is not the likely mechanism; in comparison, hypotension secondary to high-dose PTH blocks the primary diuretic effect of PTH but does not inhibit the PTH-stimulated redistribution of NHE3 and NaPi2 to the base of the microvilli.

scholarly journals Pengaruh Relaksasi Autogenik terhadap Penurunan Tekanan Darah pada Klien Hipertensi di Wilayah Kerja Puskesmas 23 Ilir Palembang Tahun 2015

2018 ◽  
Vol 11 (3) ◽  
pp. 192
Author(s):  
Sasono Mardiono
Keyword(s):  
Blood Pressure ◽  
Health Centers ◽  
P Value ◽  
Relaxation Techniques ◽  
Arterial Blood ◽  
Therapy Technique ◽  
Lower Blood ◽  
Post Test ◽  
Autogenic Relaxation ◽  
Control Body

Hypertension is an increasing arterial blood pressure which is abnormally persistent when systolic blood pressure equal to or greater than 140 mmHg and diastolic equal to or greater than 90 mmHg. Medical management of clients with hypertension were not only by pharmacological methods solely, but also by non-pharmacological treatments. One non pharmacology therapy technique, that can lowers blood pressure, was autogenic relaxation. Relaxation is autogenic relaxation specific which implies that you have the ability to control body functions, such as heart rate, blood pressure and blood flow. The design of this research was quasi experiment with the approach pre and post test only design. The purpose of this study was to determine the effect of autogenic relaxation to decrease blood pressure in hypertensive clients in the region of Palembang Ilir 23 health centers in 2015. The sample in this study was accidental sampling. Autogenic relaxation on the respondent performed three times and measured blood pressure as much as six times. Statistical test used T Dependent. The result of this research are there were some effects of autogenic relaxation namely the decreasing of blood pressure (p value = 0.000). It was concluded that there was effect of autogenic relaxation on decreasing blood pressure of hypertension clients. Based on the results of this study are expected to autogenic relaxation techniques can be applied to lower blood pressure in hypertensive clients. And to disseminate the research results to the clients of hypertension, so people know the benefits of hypertension autogenic relaxation in lowering blood pressure.

Abstract MP61: Sex Difference In The Response Of Human Renal Proximal Tubule Cells To A Nephrotoxic Agent.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Shaun Moore ◽  
Megha Kumar ◽  
Daniel Yaqub ◽  
John J Gildea ◽  
Robin Felder ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Proximal Tubule ◽  
Dopamine D2 Receptor ◽  
Renal Proximal Tubule ◽  
Ki 67 ◽  
Proximal Tubule Cells ◽  
Renal Inflammation ◽  
Males And Females ◽  
Tubule Cells ◽  
Renal Proximal Tubule Cells

Our previous work indicated that the renal dopamine D2 receptor (D2R) has a significant role in regulating renal inflammation and injury, as well as in blood pressure control. In mice, D2R has protective effects in the kidney by limiting the inflammatory and fibrotic reaction; impaired D2R function results in renal inflammation and damage. Some common single nucleotide polymorphisms (SNPs; rs 6276 and 6277) in the human DRD2 gene are associated with decreased D 2 R expression and function and high blood pressure. To determine the effects of the presence of SNPs in the response to the nephrotoxic aristolochic acid (AA, 5μg/ml, 24 h), we studied immortalized human renal proximal tubule cells isolated from normal tissue of nephrectomies and genotyped for DRD2 SNPs and DRD2 wild-type (WT). We also determined whether this response is sex dependent. D2R protein was higher in male than in female WT (135±5 vs 100±4%; n=3/group; P<0.04) and lower in males with SNPs (43±2%, P<0.05) and females with SNPs (23±2%,P<0.05), compared with their respective WT counterparts. In both male groups (WT and SNPs), AA increased D2R protein by 80-100% but had no effect in WT females and increased ~50% in females with SNPs. The TNFα mRNA was higher in males with WT and SNPs which was increased by AA 9-10-fold in WT males and females but only 2-3-fold in those with SNPs. The TGFβ mRNA was similar in WT males and females and increased to the same extent in both groups with SNPs and was not affected by AA in all groups. Col1a1 mRNA was higher (30%) in WT males and females than those with SNPs; AA decreased Col1a1 mRNA in all groups. FN1 mRNA was higher (30-40%) in males and females with SNPs than WT; AA increased FN1 mRNA only in males and females with SNPs. The mRNA expression of the cell proliferation marker Ki-67 was higher in WT females than WT males (1.5-2-fold) and higher with SNPs than WT in both groups; AA increased Ki-67 mRNA in both groups and to a greater extent in males than in females. Taken together our data indicate that the presence of DRD2 SNPs affects the baseline expression of inflammatory and fibrotic factors and the response to AA is dependent on both sex and the presence of DRD2 SNPs. These data may have potential clinical translation since rs6276/6277 is commonly expressed (42%/23%) in the human population.

Study of Antihypertensive Activity of Anvillea radiata in L-Name-Induced Hypertensive Rats and HPLC-ESI-MS Analysis

2020 ◽  
Vol 20 (7) ◽  
pp. 1059-1072
Author(s):  
Mourad Akdad ◽  
Mohammed Ajebli ◽  
Andrea Breuer ◽  
Farid Khallouki ◽  
Robert W. Owen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Administration ◽  
Antihypertensive Activity ◽  
Hypertensive Rats ◽  
Esi Ms ◽  
Vasorelaxant Effect ◽  
Aerial Parts ◽  
Arterial Blood ◽  
Ms Analysis ◽  
Ca2 Channels

Objective: This study aimed to evaluate the effect of the aqueous extract of Anvillea radiate (A. radiata) aerial parts (AEAR) on arterial blood pressure in normotensive and hypertensive rats. Methods: The effect of the acute and sub-chronic administration of AEAR on the following blood pressure parameters: systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP), and heart rate (HR) was evaluated in normotensive and L-NAME induced hypertensive rats. In the second experiment, the vasorelaxant effect of AEAR was assessed in isolated aortic rings from rats with functional endothelium pre-contracted with epinephrine (EP) or KCl, and six antagonists/ inhibitors were used to explore the mechanisms of action involved in the vasorelaxant effect. In order to determine the phytochemical contents of Anvillea radiata, HPLC-ESI-MS analysis was conducted. Results: Daily oral administration of AEAR (100 mg/kg) provoked a significant decrease in SBP, MBP, and DBP without affecting HR in hypertensive rats. In addition, AEAR (0.08-0.64 mg/ml) revealed a vasorelaxant effect in thoracic aortic rings pre-contracted by EP (10 μM) or KCl (80 mM). This effect was reduced in the presence of Nifedipine, L-Name or Methylene blue. The polyphenolic compounds of AEAR were determined. Conclusion: This study revealed that AEAR possesses a potent antihypertensive activity and its vasorelaxant activity seems to be mediated through Ca2+ channels, direct nitric oxide (NO), and NO/cGMP pathways. Chlorogenic acid and caffeic acid identified in A. radiata could be at least partially responsible for the antihypertensive activity of this extract.

Platelet-activating factor and solute transport processes in the kidney

2003 ◽  
Vol 284 (2) ◽  
pp. F274-F281 ◽  
Author(s):  
Rajash K. Handa ◽  
Jack W. Strandhoy ◽  
Carlos E. Giammattei ◽  
Shelly E. Handa
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Proximal Tubule ◽  
Sodium Transport ◽  
Platelet Activating Factor ◽  
Systemic Blood Pressure ◽  
Systemic Blood ◽  
Arterial Blood ◽  
Oxide Synthase ◽  
Cytochrome P 450

We examined the hemodynamic and tubular transport mechanisms by which platelet-activating factor (PAF) regulates salt and water excretion. In anesthetized, renally denervated male Wistar rats, with raised systemic blood pressure and renal arterial blood pressure maintained at normal levels, intrarenal PAF infusion at 2.5 ng · min−1 · kg−1resulted in a small fall in systemic blood pressure (no change in renal arterial blood pressure) and an increase in renal blood flow and urinary water, sodium, and potassium excretion rates. The PAF-induced changes in cardiovascular and renal hemodynamic function were abolished and renal excretory function greatly attenuated by treating rats with a nitric oxide synthase inhibitor. To determine whether a tubular site of action was involved in the natriuretic effect of PAF, cortical proximal tubules were enzymatically dissociated from male Wistar rat kidneys, and oxygen consumption rates (Qo 2) were used as an integrated index of transcellular sodium transport. PAF at 1 nM maximally inhibited Qo 2 in both untreated and nystatin-stimulated (sodium entry into renal cell is not rate limiting) proximal tubules by ∼20%. Blockade of PAF receptors or Na+-K+-ATPase pump activity with BN-52021 or ouabain, respectively, abolished the effect of PAF on nystatin-stimulated proximal tubule Qo 2. Inhibition of nitric oxide synthase or guanylate cyclase systems did not alter PAF-mediated inhibition of nystatin-stimulated proximal tubule Qo 2, whereas phospholipase A2 or cytochrome- P-450 monooxygenase inhibition resulted in a 40–60% reduction. These findings suggest that stimulation of PAF receptors on the proximal tubule decreases transcellular sodium transport by activating phospholipase A2 and the cytochrome- P-450 monooxygenase pathways that lead to the inhibition of an ouabain-sensitive component of the basolateral Na+-K+-ATPase pump. Thus PAF can activate both an arachidonate pathway-mediated suppression of proximal tubule sodium transport and a nitric oxide pathway-mediated dilatory action on renal hemodynamics that likely contributes to the natriuresis and diuresis observed in vivo.

Sign in / Sign up

Export Citation Format

Share Document