scholarly journals Central and peripheral slow-pressor mechanisms contributing to Angiotensin II-salt hypertension in rats

2017 ◽  
Vol 114 (2) ◽  
pp. 233-246 ◽  
Author(s):  
Jiao Lu ◽  
Hong-Wei Wang ◽  
Monir Ahmad ◽  
Marzieh Keshtkar-Jahromi ◽  
Mordecai P Blaustein ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Adrenal Cortex ◽  
Salt Intake ◽  
Plasma Corticosterone ◽  
High Salt ◽  
Ang Ii ◽  
Intracerebroventricular Infusion ◽  
High Salt Intake ◽  
Endogenous Ouabain ◽  
Salt Hypertension

AbstractAimsHigh salt intake markedly enhances hypertension induced by angiotensin II (Ang II). We explored central and peripheral slow-pressor mechanisms which may be activated by Ang II and salt.Methods and resultsIn protocol I, Wistar rats were infused subcutaneously with low-dose Ang II (150 ng/kg/min) and fed regular (0.4%) or high salt (2%) diet for 14 days. In protocol II, Ang II-high salt was combined with intracerebroventricular infusion of mineralocorticoid receptor (MR) blockers (eplerenone, spironolactone), epithelial sodium channel (ENaC) blocker (benzamil), angiotensin II type 1 receptor (AT1R) blocker (losartan) or vehicles. Ang II alone raised mean arterial pressure (MAP) ∼10 mmHg, but Ang II-high salt increased MAP ∼50 mmHg. Ang II-high salt elevated plasma corticosterone, aldosterone and endogenous ouabain but not Ang II alone. Both Ang II alone and Ang II-high salt increased mRNA and protein expression of CYP11B2 (aldosterone synthase gene) in the adrenal cortex but not of CYP11B1 (11-β-hydroxylase gene). In the aorta, Ang II-high salt increased sodium-calcium exchanger-1 (NCX1) protein. The Ang II-high salt induced increase in MAP was largely prevented by central infusion of MR blockers, benzamil or losartan. Central blockades significantly lowered plasma aldosterone and endogenous ouabain and markedly decreased Ang II-high salt induced CYP11B2 mRNA expression in the adrenal cortex and NCX1 protein in the aorta.ConclusionThese results suggest that in Ang II-high salt hypertension, MR-ENaC-AT1R signalling in the brain increases circulating aldosterone and endogenous ouabain, and arterial NCX1. These factors can amplify blood pressure responses to centrally-induced sympatho-excitation and thereby contribute to severe hypertension.

Abstract P249: Central Nervous System Control of Plasma Aldosterone and Endogenous Ouabain in Angiotensin II-Salt Hypertension

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Jiao Lu ◽  
Hong-Wei Wang ◽  
Marzieh Keshtkar-Jahromi ◽  
John M Hamlyn ◽  
Frans H Leenen
Keyword(s):  
Adrenal Cortex ◽  
Salt Intake ◽  
Plasma Corticosterone ◽  
High Salt ◽  
System Control ◽  
Ang Ii ◽  
High Salt Diet ◽  
High Salt Intake ◽  
Endogenous Ouabain ◽  
Salt Hypertension

High salt intake markedly enhances hypertension induced by Ang II. We evaluated peripheral mechanisms which may amplify central mechanisms activated by Ang II-salt. In the 1 st exp, Wistar rats were sc infused with Ang II at low dose of 150 ng/kg/min together with 2% high salt diet for 14 days. In the 2 nd exp, MR blockers (eplerenone, spironolactone), ENaC blocker (benzamil), AT 1 R blocker (losartan) or vehicles (Veh) were icv infused combined with Ang II-salt. BP was recorded by telemetry. Plasma corticosterone (Cor), aldosterone (aldo) and endogenous ouabain (EO) were measured by RIA. Gene expression was assessed by real-time qPCR. Ang II alone caused a small increase in MAP (112±1 vs. 99±1 mmHg), but BP was markedly increased by Ang II-salt (152±4 mmHg, P<0.05 vs. others). BP increases to Ang II-salt were largely inhibited by central infusion of MR blockers, benzamil or losartan. Only Ang II together with salt increased plasma aldo, Cor and EO. In the adrenal cortex, both Ang II alone and Ang II-salt increased CYP11B2 expression but neither affected CYP11B1, Hsd3b1 or AT 1 R mRNA expression. Central blockades significantly (p<0.05) lowered plasma aldo and EO in rats on Ang II-salt. Central blockades had no effect on Hsd3b1, CYP11B1 and AT 1 R mRNA but markedly decreased Ang II-salt induced CYP11B2 expression in the adrenal cortex. Together, these results suggest that in Ang II-salt hypertension, Ang II-AT 1 R signaling and MR-ENaC pathway in the brain increase plasma aldo and EO, which may amplify BP responses to central mechanisms and contribute to severe hypertension by Ang II-salt vs Ang II alone.

Central infusion of aliskiren prevents sympathetic hyperactivity and hypertension in Dahl salt-sensitive rats on high salt intake

2012 ◽  
Vol 302 (7) ◽  
pp. R825-R832 ◽  
Author(s):  
Bing S. Huang ◽  
Roselyn A. White ◽  
Li Bi ◽  
Frans H. H. Leenen
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
Receptor Blocker ◽  
Ang Ii ◽  
Sympathetic Hyperactivity ◽  
Direct Renin Inhibitor ◽  
Intracerebroventricular Infusion ◽  
High Salt Intake ◽  
The Brain

Central infusion of an angiotensin type 1 (AT1) receptor blocker prevents sympathetic hyperactivity and hypertension in Dahl salt-sensitive (S) rats on high salt. In the present study, we examined whether central infusion of a direct renin inhibitor exerts similar effects. Intracerebroventricular infusion of aliskiren at the rate of 0.05 mg/day markedly inhibited the increase in ANG II levels in the cerebrospinal fluid and in blood pressure (BP) caused by intracerebroventricular infusion of rat renin. In Dahl S rats on high salt, intracerebroventricular infusion of aliskiren at 0.05 and 0.25 mg/day for 2 wk similarly decreased resting BP in Dahl S rats on high salt. In other groups of Dahl S rats, high salt intake for 2 wk increased resting BP by ∼25 mmHg, enhanced pressor and sympathoexcitatory responses to air-stress, and desensitized arterial baroreflex function. All of these effects were largely prevented by intracerebroventricular infusion of aliskiren at 0.05 mg/day. Aliskiren had no effects in rats on regular salt. Neither high salt nor aliskiren affected hypothalamic ANG II content. These results indicate that intracerebroventricular infusions of aliskiren and an AT1 receptor blocker are similarly effective in preventing salt-induced sympathetic hyperactivity and hypertension in Dahl S rats, suggesting that renin in the brain plays an essential role in the salt-induced hypertension. The absence of an obvious increase in hypothalamic ANG II by high salt, or decrease in ANG II by aliskiren, suggests that tissue levels do not reflect renin-dependent ANG II production in sympathoexcitatory angiotensinergic neurons.

Hemodynamics, fluid volume, and hormonal responses to chronic high-salt intake in dogs

1990 ◽  
Vol 259 (6) ◽  
pp. H1629-H1636 ◽  
Author(s):  
J. E. Krieger ◽  
J. F. Liard ◽  
A. W. Cowley
Keyword(s):  
Angiotensin Ii ◽  
Salt Intake ◽  
Peripheral Resistance ◽  
Plasma Renin ◽  
Total Body Weight ◽  
High Salt ◽  
Plasma Sodium ◽  
Plasma Protein Concentration ◽  
Hormonal Responses ◽  
High Salt Intake

The sequential hemodynamics, fluid and electrolyte balances, and the hormonal responses to a 7-day high-salt (NaCl) intake were investigated in sodium-depleted conscious dogs (n = 6). Studies were carried out in metabolic cages mounted on sensitive load cells, which enabled continuous 24 h/day monitoring of total body weight (TBW) as an index of changes in body water. Beat-by-beat hemodynamics were determined 24 h/day. Water (700 ml/day iv) intake was maintained constant. Daily fluid and electrolyte balances and hormonal analyses were performed. An increase of daily salt intake from 8 to 120 meq increased TBW 251 +/- 44 g (P less than 0.05), which was sustained thereafter. Average 24-h mean arterial pressure (MAP) and heart rate (HR) remained unchanged. Average cardiac output (CO) increased 11% (P less than 0.05) above control values by day 2, while total peripheral resistance (TPR) decreased proportionally. CO and TPR returned to control values only when low salt was resumed. Blood volume (BV) was unchanged on day 2 as indicated by direct measurement of BV (51Cr-labeled red blood cells) or by analysis of plasma protein concentration. A 92-meq (P less than 0.05) sodium retention was observed initially, and plasma sodium concentration increased slightly. Plasma renin activity, angiotensin II, and aldosterone levels decreased significantly, whereas vasopressin and atrial natriuretic peptide levels remained unchanged. In summary, chronic high-salt intake resulted in a net retention of water and sodium with no changes in MAP, HR, or BV. The rise in CO was offset by a reduction in TPR, which appeared at least in part related to angiotensin II suppression.

Enhanced intrarenal receptor-mediated prorenin activation in chronic progressive anti-thymocyte serum nephritis rats on high salt intake

2012 ◽  
Vol 303 (1) ◽  
pp. F130-F138 ◽  
Author(s):  
Yanjie Huang ◽  
Tatsuo Yamamoto ◽  
Taro Misaki ◽  
Hiroyuki Suzuki ◽  
Akashi Togawa ◽  
...  
Keyword(s):  
Apical Membrane ◽  
Salt Intake ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
High Salt ◽  
Ang Ii ◽  
Kidney Fibrosis ◽  
High Salt Intake ◽  
Collecting Ducts

Despite suppression of the circulating renin-angiotensin system (RAS), high salt intake (HSI) aggravates kidney injury in chronic kidney disease. To elucidate the effect of HSI on intrarenal RAS, we investigated the levels of intrarenal prorenin, renin, (pro)renin receptor (PRR), receptor-mediated prorenin activation, and ANG II in chronic anti-thymocyte serum (ATS) nephritic rats on HSI. Kidney fibrosis grew more severe in the nephritic rats on HSI than normal salt intake. Despite suppression of plasma renin and ANG II, marked increases in tubular prorenin and renin proteins without concomitant rises in renin mRNA, non-proteolytically activated prorenin, and ANG II were noted in the nephritic rats on HSI. Redistribution of PRR from the cytoplasm to the apical membrane, along with elevated non-proteolytically activated prorenin and ANG II, was observed in the collecting ducts and connecting tubules in the nephritic rats on HSI. Olmesartan decreased cortical prorenin, non-proteolytically activated prorenin and ANG II, and apical membranous PRR in the collecting ducts and connecting tubules, and attenuated the renal lesions. Cell surface trafficking of PRR was enhanced by ANG II and was suppressed by olmesartan in Madin-Darby canine kidney cells. These data suggest the involvement of the ANG II-dependent increase in apical membrane PRR in the augmentation of intrarenal binding of prorenin and renin, followed by nonproteolytic activation of prorenin, enhancement of renin catalytic activity, ANG II generation, and progression of kidney fibrosis in the nephritic rat kidneys on HSI. The origin of the increased tubular prorenin and renin remains to be clarified. Further studies measuring the urinary prorenin and renin are needed.

Cardiac sympathetic afferent stimulation induces salt-sensitive sympathoexcitation through hypothalamic epithelial Na+ channel activation

2015 ◽  
Vol 308 (5) ◽  
pp. H530-H539 ◽  
Author(s):  
Koji Ito ◽  
Yoshitaka Hirooka ◽  
Kenji Sunagawa
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Salt Intake ◽  
Receptor Activation ◽  
High Salt ◽  
Salt Diet ◽  
Intracerebroventricular Infusion ◽  
High Salt Intake ◽  
Tnf Α ◽  
Excitatory Responses

The cardiac sympathetic afferent (CSA), which plays an important role in heart-brain communication for sympathoexcitation, is stimulated in heart failure. Additionally, high salt intake leads to further sympathoexcitation due to activation of hypothalamic epithelial Na+ channels (ENaCs) in heart failure. In the present study, we stimulated the CSA in adult male mice by epicardial application of capsaicin and using ethanol as a control to determine whether CSA stimulation led to activation of hypothalamic ENaCs, resulting in salt-induced sympathoexcitation. Three days after capsaicin treatment, an upregulation of hypothalamic α-ENaCs, without activation of mineralocorticoid receptors, was observed. We also examined expression levels of the known ENaC activator TNF-α. Hypothalamic TNF-α increased in capsaicin-treated mice, whereas intracerebroventricular infusion of the TNF-α blocker etanercept prevented capsaicin-induced upregulation of α-ENaCs. To examine brain arterial pressure (AP) sensitivity toward Na+, we performed an intracerebroventricular infusion of high Na+-containing (0.2 M) artificial cerebrospinal fluid. AP and heart rate were significantly increased in capsaicin-treated mice compared with control mice. CSA stimulation also caused excitatory responses with high salt intake. Compared with a regular salt diet, the high-salt diet augmented AP, heart rate, and 24-h urinary norepinephrine excretion, which is an indirect marker of sympathetic activity with mineralocorticoid receptor activation, in capsaicin-treated mice but not in ethanol-treated mice. Treatment with etanercept or the ENaC blocker benzamil prevented these salt-induced excitatory responses. In summary, we show that CSA stimulation leads to an upregulation of hypothalamic α-ENaCs mediated via an increase in TNF-α and results in increased salt sensitivity.

scholarly journals High-Salt Intake Induces Cardiomyocyte Hypertrophy in Rats in Response to Local Angiotensin II Type 1 Receptor Activation

2014 ◽  
Vol 144 (10) ◽  
pp. 1571-1578 ◽  
Author(s):  
Isis A. Katayama ◽  
Rafael C. Pereira ◽  
Ellen P. B. Dopona ◽  
Maria H. M. Shimizu ◽  
Luzia N. S. Furukawa ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Salt Intake ◽  
Receptor Activation ◽  
High Salt ◽  
Cardiomyocyte Hypertrophy ◽  
High Salt Intake

scholarly journals ROS Production Is Increased in the Kidney but Not in the Brain of Dahl Rats With Salt Hypertension Elicited in Adulthood

2015 ◽  
pp. 303-312 ◽  
Author(s):  
M. VOKURKOVÁ ◽  
H. RAUCHOVÁ ◽  
L. ŘEZÁČOVÁ ◽  
I. VANĚČKOVÁ ◽  
J. ZICHA
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Nadph Oxidase ◽  
Salt Intake ◽  
Renal Medulla ◽  
High Salt ◽  
Ros Production ◽  
High Salt Intake ◽  
Salt Hypertension ◽  
The Brain

Enhanced production of superoxide radicals by nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase in the brain and/or kidney of salt hypertensive Dahl rats has been proposed to participate in the pathogenesis of this form of experimental hypertension. Most information was obtained in young Dahl salt-sensitive (DS) rats subjected to high salt intake prior to sexual maturation. Therefore, the aim of our study was to investigate whether salt hypertension induced in adult DS rats is also accompanied with a more pronounced oxidative stress in the brain or kidney as compared to Dahl salt-resistant (DR) controls. NADPH oxidase activity as well as the content of thiobarbituric acid-reactive substances (TBARS) and conjugated dienes (oxidative index), which indicate a degree of lipid peroxidation, were evaluated in two brain regions (containing either hypothalamic paraventricular nucleus or rostral ventrolateral medulla) as well as in renal medulla and cortex. High salt intake induced hypertension in DS rats but did not modify blood pressure in DR rats. DS and DR rats did not differ in NADPH oxidase-dependent production of ROS, TBARS content or oxidative index in either part of the brain. In addition, high-salt diet did not change significantly any of these brain parameters. In contrast, the enhanced NADPH oxidase-mediated ROS production (without significant signs of increased lipid peroxidation) was detected in the renal medulla of salt hypertensive DS rats. Our findings suggest that there are no signs of enhanced oxidative stress in the brain of adult Dahl rats with salt hypertension induced in adulthood.

Depressor effect of chymase inhibitor in mice with high salt-induced moderate hypertension

2015 ◽  
Vol 309 (11) ◽  
pp. H1987-H1996 ◽  
Author(s):  
Sankar Devarajan ◽  
Eiji Yahiro ◽  
Yoshinari Uehara ◽  
Shigehisa Habe ◽  
Akira Nishiyama ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Drinking Water ◽  
Salt Intake ◽  
Renin Angiotensin System ◽  
High Salt ◽  
Ang Ii ◽  
Relative Contribution ◽  
High Salt Intake ◽  
Chymase Inhibitor ◽  
Depressor Effect

The aim of the present study was to determine whether long-term high salt intake in the drinking water induces hypertension in wild-type (WT) mice and whether a chymase inhibitor or other antihypertensive drugs could reverse the increase of blood pressure. Eight-week-old male WT mice were supplied with drinking water containing 2% salt for 12 wk (high-salt group) or high-salt drinking water plus an oral chymase inhibitor (TPC-806) at four different doses (25, 50, 75, or 100 mg/kg), captopril (75 mg/kg), losartan (100 mg/kg), hydrochlorothiazide (3 mg/kg), eplerenone (200 mg/kg), or amlodipine (6 mg/kg). Control groups were given normal water with or without the chymase inhibitor. Blood pressure and heart rate gradually showed a significant increase in the high-salt group, whereas a dose-dependent depressor effect of the chymase inhibitor was observed. There was also partial improvement of hypertension in the losartan- and eplerenone-treated groups but not in the captopril-, hydrochlorothiazide-, and amlodipine-treated groups. A high salt load significantly increased chymase-dependent ANG II-forming activity in the alimentary tract. In addition, the relative contribution of chymase to ANG II formation, but not actual average activity, showed a significant increase in skin and skeletal muscle, whereas angiotensin-converting enzyme-dependent ANG II-forming activity and its relative contribution were reduced by high salt intake. Plasma and urinary renin-angiotensin system components were significantly increased in the high-salt group but were significantly suppressed in the chymase inhibitor-treated group. In conclusion, 2% salt water drinking for 12 wk caused moderate hypertension and activated the renin-angiotensin system in WT mice. A chymase inhibitor suppressed both the elevation of blood pressure and heart rate, indicating a definite involvement of chymase in salt-sensitive hypertension.

Sign in / Sign up

Export Citation Format

Share Document