scholarly journals Chronic Metabolic Acidosis Elicits Hypertension via Upregulation of Intrarenal Angiotensin II and Induction of Oxidative Stress

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 2
Author(s):  
Dinesh Aryal ◽  
Tithi Roy ◽  
Jean Christopher Chamcheu ◽  
Keith E. Jackson
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Metabolic Acidosis ◽  
Angiotensin Ii ◽  
Serum Sodium ◽  
Tap Water ◽  
Plasma Renin ◽  
Urinary Sodium ◽  
Chronic Metabolic Acidosis ◽  
Blood Ph

Chronic metabolic acidosis (CMA) can be a consequence of persistent hypertension but could potentially play a role in invoking hypertension. Currently, there is a scarcity of studies examining the outcome of induced chronic acidosis on blood pressure regulation. This study investigates CMA as a cause of hypertension. Chronic acidosis was induced in Sprague Dawley rats (100–150 g) by providing a weak acid solution of 0.28 M ammonium chloride (NH4Cl) in tap water for 8 weeks. To determine whether the rats were acidotic, blood pH was measured, while blood pressure (BP) was monitored by tail-cuff plethysmography weekly. Rats were divided into five groups: control, CMA, CMA ± spironolactone, captopril, and tempol. Serum sodium and potassium; renal interstitial fluid (for Angiotensin II concentration); and kidney proximal tubules (for Na+/K+ ATPase- α1 concentration) were analyzed. Reactive oxygen species (ROS) were detected in renal cortical homogenates using electron paramagnetic resonance (EPR). In the CMA rats, a sustained elevation in mean arterial pressure (MAP) associated with a significant decrease in blood pH was observed compared to that of control over the 8 weeks. A significant decrease in MAP was observed in acidotic rats treated with captopril/tempol, whereas spironolactone treatment caused no decrease in MAP as compared to that of the CMA group. The interstitial angiotensin II was increased in the CMA group but decreased in the CMA with captopril and tempol groups. In addition, the urinary sodium was decreased, and the serum sodium levels increased significantly in the CMA groups as compared to that of control. However, the acidotic groups with captopril and tempol showed reduced levels of serum sodium and an elevation in urinary sodium as compared to that of the CMA group. In addition, there was a significant increase in plasma renin and no change in plasma aldosterone in the CMA group with no significant differences in plasma renin or aldosterone observed during spironolactone, captopril, or tempol treatments. The increased expression of Na+/K+ ATPase-α1 in the CMA group suggests that active transport of Na+ to the blood could be causative of the observed hypertension. Furthermore, the EPR analysis confirmed an elevation in superoxide (O2-) radical levels in the CMA group, but the tempol/captopril treated acidotic groups showed less (O2-) compared to that of either the CMA group or control. Taken together, our data suggest that induction of CMA could potentially be causative of hypertension, while the mechanisms underlying the increased BP could be through the activation of intrarenal Ang II and induction of oxidative stress.

Effect of enalapril (MK-421), an orally active angiotensin I converting enzyme inhibitor, on blood pressure, active and inactive plasma renin, urinary prostaglandin E2, and kallikrein excretion in conscious rats

1984 ◽  
Vol 62 (1) ◽  
pp. 116-123 ◽  
Author(s):  
Ernesto L. Schiffrin ◽  
Jolanta Gutkowska ◽  
Gaétan Thibault ◽  
Jacques Genest
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Ace Inhibition ◽  
Renin Activity ◽  
Prostaglandin E ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Angiotensin I Converting Enzyme

The angiotensin I converting enzyme (ACE) inhibitor enalapril (MK-421), at a dose of 1 mg/kg or more by gavage twice daily, effectively inhibited the pressor response to angiotensin I for more than 12 h and less than 24 h. Plasma renin activity (PRA) did not change after 2 or 4 days of treatment at 1 mg/kg twice daily despite effective ACE inhibition, whereas it rose significantly at 10 mg/kg twice daily. Blood pressure fell significantly and heart rate increased in rats treated with 10 mg/kg of enalapril twice daily, a response which was abolished by concomitant angiotensin II infusion. However, infusion of angiotensin II did not prevent the rise in plasma renin. Enalapril treatment did not change urinary immunorcactive prostaglandin E2 (PGE2) excretion and indomethacin did not modify plasma renin activity of enalapril-treated rats. Propranolol significantly reduced the rise in plasma renin in rats receiving enalapril. None of these findings could be explained by changes in the ratio of active and inactive renin. Water diuresis, without natriuresis and with a decrease in potassium urinary excretion, occurred with the higher dose of enalapril. Enalapril did not potentiate the elevation of PRA in two-kidney one-clip Goldblatt hypertensive rats. In conclusion, enalapril produced renin secretion, which was in part β-adrenergically mediated. The negative short feedback loop of angiotensin II and prostaglandins did not appear to be involved. A vasodilator effect, apparently independent of ACE inhibition, was found in intact conscious sodium-replete rats.

scholarly journals A Subpressor Dose of Angiotensin II Elevates Blood Pressure in a Normotensive Rat Model by Oxidative Stress

2015 ◽  
pp. 153-159 ◽  
Author(s):  
M. M. GOVENDER ◽  
A. NADAR
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Mrna Expression ◽  
Rat Model ◽  
Wistar Rat ◽  
Control Group ◽  
Sod Activity ◽  
Male Wistar Rats ◽  
Experimental Group

Oxidative stress is an imbalance between free radicals and antioxidants, and is an important etiological factor in the development of hypertension. Recent experimental evidence suggests that subpressor doses of angiotensin II elevate oxidative stress and blood pressure. We aimed to investigate the oxidative stress related mechanism by which a subpressor dose of angiotensin II induces hypertension in a normotensive rat model. Normotensive male Wistar rats were infused with a subpressor dose of angiotensin II for 28 days. The control group was sham operated and infused with saline only. Plasma angiotensin II and H2O2 levels, whole-blood glutathione peroxidase, and AT-1a, Cu/Zn SOD, and p22phox mRNA expression in the aorta was assessed. Systolic and diastolic blood pressures were elevated in the experimental group. There was no change in angiotensin II levels, but a significant increase in AT-1a mRNA expression was found in the experimental group. mRNA expression of p22phox was increased significantly and Cu/Zn SOD decreased significantly in the experimental group. There was no significant change to the H2O2 and GPx levels. Angiotensin II manipulates the free radical-antioxidant balance in the vasculature by selectively increasing O2− production and decreasing SOD activity and causes an oxidative stress induced elevation in blood pressure in the Wistar rat.

scholarly journals Long-term exercise attenuates blood pressure responsiveness and modulates kidney angiotensin II signalling and urinary sodium excretion in SHR

2011 ◽  
Vol 12 (4) ◽  
pp. 394-403 ◽  
Author(s):  
Silmara Ciampone ◽  
Rafael Borges ◽  
Ize P de Lima ◽  
Flávia F Mesquita ◽  
Elizabeth C Cambiucci ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Exercise Training ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Receptor Expression ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

Observations have been made regarding the effects of long-term exercise training on blood pressure, renal sodium handling and renal renin–angiotensin–aldosterone (RAS) intracellular pathways in conscious, trained Okamoto–Aoki spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKy) normotensive rats, compared with appropriate age-matched sedentary SHR and WKy. To evaluate the influence of exercise training on renal function and RAS, receptors and intracellular angiotensin II (AngII) pathway compounds were used respectively, and lithium clearance and western blot methods were utilised. The current study demonstrated that increased blood pressure in SHR was blunted and significantly reduced by long-term swim training between the ages of 6 and 16 weeks. Additionally, the investigators observed an increased fractional urinary sodium excretion in trained SHR (SHRT) rats, compared with sedentary SHR (SHRS), despite a significantly decreased creatinine clearance (CCr). Furthermore, immunoblotting analysis demonstrated a decreased expression of AT1R in the entire kidney of TSHR rats, compared with SSHR. Conversely, the expression of the AT2R, in both sedentary and trained SHR, was unchanged. The present study may indicate that, in the kidney, long-term exercise exerts a modulating effect on AngII receptor expression. In fact, the present study indicates an association of increasing natriuresis, reciprocal changes in renal AngII receptors and intracellular pathway proteins with the fall in blood pressure levels observed in TSHR rats compared with age-matched SSHR rats.

Role of endothelin receptors in the hypertensive state of kinin B2 knockout mice subjected to a high-salt diet

2002 ◽  
Vol 103 (s2002) ◽  
pp. 380S-384S ◽  
Author(s):  
Isabelle BROCHU ◽  
Julie LABONTÉ ◽  
Ghassan BKAILY ◽  
Pedro D'ORLÉANS-JUSTE
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Tap Water ◽  
Blood Pressure Measurement ◽  
Rna Extraction ◽  
Angiotensin Receptors ◽  
Rt Pcr ◽  
Arterial Blood

Mice with disruption of the kinin B2 receptor (B2KO mice) are sensitive to salt-rich diets, which causes hypertension. The aim of the study was to assess the role of endothelin-1 (ET-1) and angiotensin-II in hypertensive B2KO mice on a salt-rich diet. We also wanted to verify if there is an upregulation of the mRNA expression of the precursors or receptors for these hormones. Two groups of B2KO mice (20–25g) were investigated. The first group received an 8% NaCl diet with 1% NaCl in drinking water (HS) and the second was fed with normal food with tap water (NS). The antagonists tested were the ETA receptor antagonist BQ-123 (1 and 5mg/kg), the ETB receptor antagonist BQ-788 (0.25 and 1mg/kg), the angiotensin receptor type 1 antagonist losartan (10mg/kg) and the angiotensin-converting enzyme inhibitor captopril (3mg/kg). These were injected intraperitoneally 30min prior to blood pressure measurement by the tail-cuff method. We also studied the level of expression of preproET-1, ET-1 receptors, angiotensinogen and angiotensin receptors by RNA extraction from the heart and kidneys of these mice followed by reverse transcriptase (RT)-PCR. B2KO mice (HS) were hypertensive after 8 weeks compared with B2KO mice on normal diet (HS, 93.4±1.5mmHg, n = 7; NS, 61.4±2.7mmHg, n = 7). In the HS group, the mean arterial blood pressure was significantly reduced by BQ-123 (5mg/kg) to 61.9±1.8mmHg (n = 7), by BQ-788 (1mg/kg) to 58.8±2.6mmHg (n = 6), by losartan (10mg/kg) to 73.2±1.7mmHg (n = 8) and by captopril (3mg/kg) to 86.0±2.3mmHg (n = 8). The expression studied by RT-PCR did not show any difference (either in precursors or receptors expression) between hypertensive and normal mice. The four antagonists used seemed to reverse the hypertension. These results suggest that ET-1 and angiotensin-II are probably involved in the mechanism that leads to hypertension since the effect of these hormones is probably not compensated by kinins in B2KO mice. Further studies are necessary to understand the implication of the cross-talk between these hormones in the hypertensive state.

Hypertension in Dahl salt-sensitive rats: biochemical and immunohistochemical studies

1992 ◽  
Vol 83 (1) ◽  
pp. 13-22 ◽  
Author(s):  
J. Bouhnik ◽  
J. P. Richoux ◽  
H. Huang ◽  
F. Savoie ◽  
T. Baussant ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
High Salt ◽  
Renin Activity ◽  
Deficient Diet ◽  
High Salt Diet ◽  
Salt Diet ◽  
Plasma Angiotensin

1. The renin-angiotensin and kinin-kallikrein systems of Dahl salt-sensitive and salt-resistant rats fed diets with different salt contents were analysed using biochemical and immunocytochemical techniques. 2. Blood pressure increased by 45% in salt-sensitive rats only, after 4 weeks on a high-salt diet. The plasma renin activity and plasma angiotensin II concentration remained at the same levels in salt-sensitive rats on the high-salt diet as on the normal salt diet, whereas the plasma renin activity and plasma angiotensin II concentration of salt-resistant rats fed the high-salt diet were lower. The plasma renin activity and the plasma angiotensin II concentration were elevated in both salt-resistant and salt-sensitive rats fed the salt-deficient diet but were much more elevated in salt-resistant than in salt-sensitive rats. 3. The kidney immunocytochemical data paralleled the data on plasma parameters. Salt-sensitive rats had fewer renin positive juxtaglomerular apparatuses than salt-resistant rats on the normal diet, and the increase on the sodium-deficient diet was also smaller in salt-sensitive rats. Salt-sensitive rats fed the high-salt diet and the standard diet had almost no angiotensin II immunoreactivity compared with the salt-resistant rats on the same diets. 4. The total renal kallikrein content of salt-sensitive rats was lower than that of salt-resistant rats on all three diets, as was the amount of kallikrein excreted in the urine on the standard and the high-salt diets. The differences resulted from a reduction in active kallikrein. The increase in kallikrein in salt-sensitive and salt-resistant rats on the salt-deficient diet was not significantly different. 5. There were similar changes in immunopositive kallikrein in the kidneys of salt-sensitive and salt-resistant rats with diet, with a large increase in kallikrein biosynthesis on the low-salt diet. The plasma concentration of high-molecular-mass kininogen was not significantly different in salt-sensitive and salt-resistant rats, but there was a significant increase in T-kininogen in salt-sensitive rats fed the high-salt diet. 6. In conclusion, the absence of decreases in the plasma renin activity and the plasma angiotensin II concentration in salt-sensitive rats fed the high-salt diet might partially explain the increase in blood pressure.

Angiotensin II infusion increases vasopressin, ACTH, and 11-hydroxycorticosteroid secretion

1978 ◽  
Vol 234 (1) ◽  
pp. R66-R71 ◽  
Author(s):  
D. J. Ramsay ◽  
L. C. Keil ◽  
M. C. Sharpe ◽  
J. Shinsako
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Concentration ◽  
Plasma Renin Activity ◽  
Plasma Levels ◽  
Intravenous Infusion ◽  
Plasma Renin ◽  
Acth Secretion ◽  
Plasma Vasopressin ◽  
Bilateral Carotid

The effects of intravenous infusion of Asp1. Ile5-angiotensin II on blood pressure, plasma vasopressin, ACTH and 11-hydroxycorticosteroid levels and on plasma renin activity were studied in five trained, conscious dogs. The dogs were prepared with bilateral carotid loops. Infusion of angiotensin II at rates of 5, 10, and 20 ng/kg.min raised its plasma concentration from 23 +/- 7 to 48 +/- 8, 125 +/- 8, and 187 +/- 21 pg/ml, respectively. The lowest rate of infusion was mildly pressor, the two higher rates more so. All rates of infusion promptly increased vasopressin levels and depressed renin levels. The two higher rates also stimulated ACTH, although with a latency of 30-45 min. Since the rates of infusion of angiotensin II employed produced plasma levels within the physiological range, it is suggested that peripherally generated angiotensin II may play an important role in the regulation of vasopressin, and ACTH secretion.

scholarly journals The NADPH Oxidase Isoform 1 Contributes to Angiotensin II-Mediated DNA Damage in the Kidney

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 586
Author(s):  
Anna Zimnol ◽  
Nora Spicker ◽  
Ronja Balhorn ◽  
Katrin Schröder ◽  
Nicole Schupp
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Dna Damage ◽  
Angiotensin Ii ◽  
Knockout Mice ◽  
Dna Lesions ◽  
Mouse Strains ◽  
Nadph Oxidases ◽  
Systemic Oxidative Stress ◽  
The Impact

In higher concentrations, the blood pressure regulating hormone angiotensin II leads to vasoconstriction, hypertension, and oxidative stress by activating NADPH oxidases which are a major enzymatic source of reactive oxygen species (ROS). With the help of knockout animals, the impact of the three predominant NADPH oxidases present in the kidney, i.e., Nox1, Nox2 and Nox4 on angiotensin II-induced oxidative damage was studied. Male wildtype (WT) C57BL/6 mice, Nox1-, Nox2- and Nox4-deficient mice were equipped with osmotic minipumps, delivering either vehicle (PBS) or angiotensin II, for 28 days. Angiotensin II increased blood pressure and urinary albumin levels significantly in all treated mouse strains. In Nox1 knockout mice these increases were significantly lower than in WT, or Nox2 knockout mice. In WT mice, angiotensin II also raised systemic oxidative stress, ROS formation and DNA lesions in the kidney. A local significantly increased ROS production was also found in Nox2 and Nox4 knockout mice but not in Nox1 knockout mice who further had significantly lower systemic oxidative stress and DNA damage than WT animals. Nox2 and Nox4 knockout mice had increased basal DNA damage, concealing possible angiotensin II-induced increases. In conclusion, in the kidney, Nox1 seemed to play a role in angiotensin II-induced DNA damage.

Failure of angiotensin II to suppress plasma renin activity in normotensive subjects with a positive family history of hypertension

2005 ◽  
Vol 109 (3) ◽  
pp. 311-317 ◽  
Author(s):  
Hans Herlitz ◽  
Eva Palmgren ◽  
Bengt Widgren ◽  
Mattias Aurell
Keyword(s):  
Angiotensin Ii ◽  
Family History ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Urinary Sodium ◽  
Renin Activity ◽  
Ang Ii ◽  
History Of ◽  
Family History Of Hypertension ◽  
Normotensive Subjects

The renin–angiotensin system is implicated in the pathophysiology of hypertension. Renin release is regulated by a number of factors, including circulating Ang II (angiotensin II), the so-called short feedback loop. The aim of the present study was to investigate the responsiveness of circulating Ang II on PRA (plasma renin activity) in normotensive subjects with a PFH or NFH (positive or negative family history of hypertension respectively). PRA, renal haemodynamics and urinary sodium excretion were measured during infusion of Ang II without and with pretreatment with the AT1 (Ang II type 1) receptor blocker irbesartan. Normotensive men with a PFH (n=13) and NFH (n=10), with a mean age of 38 years, were given on different occasions intravenous Ang II infusions of 0.1, 0.5 and 1.0 ng·kg−1 of body weight·min−1 before and after pretreatment with 150 mg of irbesartan once a day for 5 consecutive days. RPF (renal plasma flow) and GFR (glomerular filtration rate) were also measured. Before Ang II infusion, the PFH and NFH groups did not differ with respect to BP (blood pressure), body mass index, PRA, RBF (renal blood flow) or urinary sodium. There was no difference in BP or renal haemodynamic response to the highest Ang II dose between the groups. PRA declined with the highest Ang II dose (P<0.01) in subjects with a NFH, but not in subjects with a PFH. After treatment with irbesartan when Ang II had no effect on BP in either group, Ang II also suppressed PRA in subjects with a PFH (P<0.01), and the difference between the groups at baseline was thus eliminated. In conclusion, these findings indicate that subjects with a PFH have a defective Ang II suppression of PRA, which is corrected by AT1 receptor blockade.

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