High-salt diet upregulates kininogen and downregulates tissue kallikrein expression in Dahl-SS and SHR rats

1996 ◽  
Vol 271 (4) ◽  
pp. F824-F830 ◽  
Author(s):  
C. Wang ◽  
C. Chao ◽  
L. M. Chen ◽  
L. Chao ◽  
J. Chao
Keyword(s):  
Blood Pressure ◽  
High Salt ◽  
Transcriptional Level ◽  
Tissue Kallikrein ◽  
Mrna Levels ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Salt Loading ◽  
Salt Diet ◽  
Sd Rats

Tissue kallikrein cleaves low-molecular-weight (low-M(r)) kininogen to produce the vasoactive kinin peptide. It has been suggested that hypertensive patients with low urinary kallikrein excretion may have a defect in sodium handling. In this study, we examined the effect of a high-salt diet on the expression of tissue kallikrein and kininogen genes in Dahl salt-sensitive rats (Dahl-SS), spontaneously hypertensive rats (SHR), and normotensive Sprague-Dawley rats (SD) by Northern and Western blot analysis and radioimmunoassay. Control and experimental groups received normal and high-salt diets containing 0.4% and 8% NaCl, respectively, for 6 wk. High-salt diet induced a significant time-dependent increase of blood pressure in both strains of hypertensive rats and a slight but significant increase of blood pressure in normotensive SD rats. Hepatic kininogen mRNA levels of both Dahl-SS and SHR on a high-salt diet increased 2.4-fold and 2.0-fold, respectively, while alpha 1-antitrypsin mRNA levels were not changed in rats receiving high-salt diet. Immunoreactive total kininogen and low-M(r) kininogen (58 kDa) levels in sera increased in response to high-salt diet in both strains of hypertensive rats. In SD rats, the low-M(r) kininogen level in sera was unaltered, whereas total kininogen increased in response to high-salt diet. Tissue kallikrein mRNAs in the kidney and salivary glands of Dahl-SS, SHR, and SD rats were reduced, whereas beta-actin mRNA was not altered by high-salt diet. Similarly, immunoreactive intrarenal kallikrein levels were reduced in these rats in response to high-salt diet. These studies show that increases in blood pressure after salt loading in Dahl-SS and SHR are accompanied by increases in low-M(r) kininogen. Tissue kallikrein gene expression in hypertensive Dahl-SS and SHR and normotensive SD rats is suppressed after salt loading. These findings show that reduced renal kallikrein expression and increased kininogen expression is regulated at the transcriptional level during salt loading.

scholarly journals Association of a Disrupted Dipping Pattern of Blood Pressure with Progression of Renal Injury during the Development of Salt-Dependent Hypertension in Rats

2020 ◽  
Vol 21 (6) ◽  
pp. 2248 ◽  
Author(s):  
Abu Sufiun ◽  
Asadur Rahman ◽  
Kazi Rafiq ◽  
Yoshihide Fujisawa ◽  
Daisuke Nakano ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Circadian Rhythm ◽  
Renal Injury ◽  
Tissue Injury ◽  
Renal Tissue ◽  
High Salt ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Salt Diet ◽  
The Difference

The aim of the present study is to investigate whether a disruption of the dipping pattern of blood pressure (BP) is associated with the progression of renal injury in Dahl salt-sensitive (DSS) hypertensive rats. Seven-week-old DSS rats were fed a high salt diet (HSD; 8% NaCl) for 10 weeks, followed by a transition to a normal salt diet (NSD; 0.3% NaCl) for 4 weeks. At baseline, NSD-fed DSS rats showed a dipper-type circadian rhythm of BP. By contrast, HSD for 5 days caused a significant increase in the difference between the active and inactive periods of BP with an extreme dipper type of BP, while proteinuria and renal tissue injury were not observed. Interestingly, HSD feeding for 10 weeks developed hypertension with a non-dipper pattern of BP, which was associated with obvious proteinuria and renal tissue injury. Four weeks after switching to an NSD, BP and proteinuria were significantly decreased, and the BP circadian rhythm returned to the normal dipper pattern. These data suggest that the non-dipper pattern of BP is associated with the progression of renal injury during the development of salt-dependent hypertension.

Prolonged NOS inhibition in the brain elevates blood pressure in normotensive rats

1998 ◽  
Vol 275 (2) ◽  
pp. R410-R417 ◽  
Author(s):  
Atsushi Sakima ◽  
Hiroshi Teruya ◽  
Masanobu Yamazato ◽  
Rijiko Matayoshi ◽  
Hiromi Muratani ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
High Salt ◽  
Salt Loading ◽  
Salt Diet ◽  
Intracerebroventricular Infusion ◽  
Air Jet ◽  
Sd Rats ◽  
Low Salt ◽  
The Brain

Systemic inhibition of nitric oxide synthase (NOS) evokes hypertension, which is enhanced by salt loading, partly via augmented sympathetic activity. We investigated whether inhibition of brain NOS elevates blood pressure (BP) in normotensive rats and, if so, whether the BP elevation is enhanced by salt loading. After a 2-wk low-salt (0.3%) diet, male Sprague-Dawley (SD) rats were divided into four groups. Groups 1 and 2 received a chronic intracerebroventricular infusion of 0.5 mg ⋅ kg−1 ⋅ day−1of N G-monomethyl-l-arginine (l-NMMA), and groups 3 and 4 were given artificial cerebrospinal fluid (aCSF). Groups 1 and 3 were placed on a high-salt (8%) diet, whereas groups 2 and 4 were on a low-salt diet. On day 9or 10, group 1 showed significantly higher mean arterial pressure (MAP) in a conscious unrestrained state (129 ± 3 mmHg vs. 114 ± 3, 113 ± 1, and 108 ± 3 mmHg in groups 2, 3, and 4, respectively, P < 0.05). On a high-salt diet, response of renal sympathetic nerve activity but not of BP to air-jet stress was significantly larger in rats givenl-NMMA than in rats given aCSF (29 ± 4% vs. 19 ± 3%, P < 0.05). When the intracerebroventricular infusions were continued for 3 wk, MAP was significantly higher in rats givenl-NMMA than in rats given aCSF irrespective of salt intake, although the difference was ∼7 mmHg. Thus chronic inhibition of NOS in the brain only slightly elevates BP in SD rats. Salt loading causes a more rapid rise in BP. The mechanisms of the BP elevation and its acceleration by salt loading remain to be elucidated.

scholarly journals High salts intake, cardiovascular system and kidney in spontaneous hypertensive rats

2017 ◽  
Vol 16 (3) ◽  
pp. 62-69
Author(s):  
A. G. Kucher ◽  
O. N. Beresneva ◽  
M. M. Parastaeva ◽  
G. T. Ivanova ◽  
M. I. Zarajsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Pressure ◽  
Heart Rate ◽  
Cardiovascular System ◽  
High Salt ◽  
Myocardial Remodeling ◽  
Hypertensive Rats ◽  
Relative Level ◽  
High Salt Diet ◽  
Salt Diet

Objective. To study the influence of diet containing high or normal NaCl on the arterial blood pressure level (BP), heart rate (HR), processes of myocardial remodeling and of nuclear transcription factor kB (NFkB) expression in myocardium and kidney in spontaneously hypertensive rats (SHR). Design and methods. The two groups of male SHRs received a diet with normal (0.34 %; n = 24, control) and high content of NaCl (8.0 %; n = 25; experimental group) for 2 months. Blood pressure (BP), heart rate (HR), cardiac left ventricular mass index (LVMI), left (LKMI) and right (RKMI) kidney mass indexes were determined. Morphological study of myocardium (light microscopy), including quantitative morphometry was carried out. In part of animals the relative level of NFkB gene expression in heart and kidney tissues was studied. Results and discussion. In rats fed a diet containing 8 % NaCl BP and HR did not change significantly compared with the control. However, LVMI, RKMI, LKMI were significantly higher in high-salt diet-treated animals than in controls. The heart of high-salt diet-treated animals developed the changes leading to hypertrophy and possibly hyperplasia of cardiomyocytes. In these animals, perivascular fibrosis, significant increase of arterial wall thickness and vacuolization of smooth muscle cells were revealed. The relative level of NFKB gene expression in rats receiving high-salt diet was 33-fold higher in myocardium and 12-fold higher in kidneys than in animals fed a normal salt diet. Conclusion. The high-salt diet is not necessarily accompanied by an increase in blood pressure, but causes myocardial remodeling, apparently due to direct «toxic» effects. The negative impact on the cardiovascular system of high-salt diet is in part mediated through NFkB-associated signaling pathways. Furthermore, high NaCl diet causes activation of NFkB in the kidneys.

scholarly journals Sex dependent compensatory mechanisms to preserve blood pressure homeostasis in PGI2 receptor deficient mice

2020 ◽  
Author(s):  
Soon Yew Tang ◽  
Seán T. Anderson ◽  
Hu Meng ◽  
Dimitra Sarantopoulou ◽  
Emanuela Ricciotti ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Oxidant Stress ◽  
High Salt ◽  
Prostaglandin E ◽  
High Salt Diet ◽  
Salt Loading ◽  
Salt Diet ◽  
Female Mice ◽  
The Impact ◽  
Deficient Mice

AbstractInhibitors of microsomal prostaglandin E synthase-1 (mPges-1) are in the early phase of clinical development. Deletion of mPges-1 confers analgesia, restrains atherogenesis and fails to accelerate thrombogenesis, while suppressing prostaglandin (PG) E2, but increasing biosynthesis of prostacyclin (PGI2). In hyperlipidemic mice, this last effect represents the dominant mechanism by which mPges-1 deletion restrains thrombogenesis, while suppression of PGE2 accounts for its anti-atherogenic effect. However, the impact of mPges-1 depletion on blood pressure (BP) in this setting remains unknown.To address how differential effects on PGE2 and PGI2 might modulate salt-evoked BP responses in the absence of mPges-1, we generated mice lacking the I prostanoid (Ipr) receptor or mPges-1 on a hyperlipidemic background caused by deletion of the low density lipoprotein receptor (Ldlr KOs). Here, mPges-1 depletion significantly increased the BP response to salt loading in male Ldlr KO mice, whereas, despite the direct vasodilator properties of PGI2, Ipr deletion suppressed it. Furthermore, combined deletion of the Ipr abrogated the exaggerated BP response in male mPges-1 KO mice. Suppression of PGE2 biosynthesis was enough to explain the exaggerated BP response to salt loading by either mPges-1/Ldlr depletion or by an MPGES-1 inhibitor in mice expressing human mPGES-1. However, the lack of a hypertensive response to salt in Ipr-deficient mice was attributable to reactive activation of the atrial natriuretic peptide pathway. Interestingly, these unexpected BP phenotypes were not observed in female mice fed a high salt diet. This is attributable to the protective effect of estrogen in Ldlr KO mice and in Ipr /Ldlr DKOs. Thus, estrogen compensates for a deficiency in PGI2 to maintain BP homeostasis in response to high salt in hyperlipidemic female mice. In males, by contrast, augmented formation of ANP plays a similar compensatory role, restraining hypertension and oxidant stress in the setting of Ipr depletion. Hyperlipidemic males on a high salt diet might be at risk of a hypertensive response to mPGES-1 inhibitors.

scholarly journals Salt-induced sympathoexcitation involves vasopressin V1a receptor activation in the paraventricular nucleus of the hypothalamus

2015 ◽  
Vol 309 (11) ◽  
pp. R1369-R1379 ◽  
Author(s):  
Natalia Ribeiro ◽  
Helena do Nascimento Panizza ◽  
Karoline Martins dos Santos ◽  
Hildebrando C. Ferreira-Neto ◽  
Vagner Roberto Antunes
Keyword(s):  
Blood Pressure ◽  
High Blood Pressure ◽  
Paraventricular Nucleus ◽  
Receptor Activation ◽  
High Salt ◽  
Male Rats ◽  
Plasma Sodium ◽  
High Salt Diet ◽  
Salt Loading ◽  
Salt Diet

A high-salt diet can lead to hydromineral imbalance and increases in plasma sodium and osmolality. It is recognized as one of the major contributing factors for cardiovascular diseases such as hypertension. The paraventricular nucleus (PVN) plays a pivotal role in osmotically driven sympathoexcitation and high blood pressure, the precise mechanisms of which are not fully understood. Recent evidence indicates that AVP released from magnocellular neurons might be involved in this process. Using a combination of in vivo and in situ studies, we sought to investigate whether AVP, acting on PVN neurons, can change mean arterial pressure (MAP) and sympathetic nerve activity (SNA) in euhydrated male rats. Furthermore, we wanted to determine whether V1a receptors on PVN neurons would be involved in salt-induced sympathoexcitation and hypertension. In rats, 4 days of salt loading (NaCl 2%) elicited a significant increase in plasma osmolality (39 ± 7 mosmol/kgH2O), an increase in MAP (26 ± 2 mmHg, P < 0.001), and sympathoexcitation compared with euhydrated rats. Microinjection of AVP into the PVN of conscious euhydrated animals (100 nl, 3 μM) elicited a pressor response (14 ± 2 mmHg) and a significant increase in lumbar SNA (100 nl, 1 mM) (19 ± 5%). Pretreatment with a V1a receptor antagonist, microinjected bilaterally into the PVN of salt-loaded animals, elicited a decrease in lumbar SNA (−14 ± 5%) and MAP (−19 ± 5 mmHg), when compared with the euhydrated group. Our findings show that AVP plays an important role in modulating the salt-induced sympathoexcitation and high blood pressure, via V1a receptors, within the PVN of male rats. As such, V1a receptors in the PVN might contribute to neurogenic hypertension in individuals consuming a high-salt diet.

Fenofibrate lowers blood pressure in two genetic models of hypertension

2000 ◽  
Vol 78 (5) ◽  
pp. 367-371 ◽  
Author(s):  
Raied Khaled Shatara ◽  
Dale W Quest ◽  
Thomas W Wilson
Keyword(s):  
Blood Pressure ◽  
Weight Gain ◽  
High Salt ◽  
Lipid Lowering ◽  
Urine Protein ◽  
High Salt Diet ◽  
Salt Diet ◽  
Urine Protein Excretion ◽  
Protein Excretion ◽  
Sd Rats

Fenofibrate, a commonly used lipid lowering drug, induces the expression of the gene coding for cytochrome P450-4A, whose major product is 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE, a potassium channel antagonist, could increase or decrease blood pressure (BP). We studied the effects of four weeks of oral fenofibrate on BP, urine output (UVol), plasma renin activity (PRA), and urine protein excretion in young (4-5 weeks) stroke prone spontaneously hypertensive rats (SHRSP), older (25 weeks) SHRSP, Dahl salt sensitive rats (Dahl S) on a high salt diet, Dahl S rats on a normal salt diet, and normotensive Sprague-Dawley (SD) rats. Fenofibrate prevented the increase in BP in 4-5 week old SHRSP, reduced BP in 25 week old SHRSP, but had no effect on BP in normotensive SD rats. Similarly, fenofibrate prevented the increase in BP in Dahl S rats on a high salt diet, but had no effect in Dahl S rats on a low salt diet. Fenofibrate increased UVol (and reduced weight gain) in young SHRSP and tended to increase it in other groups. It also increased PRA 2 to 5-fold in all groups except older SHRSP. Young SHRSP receiving fenofibrate excreted significantly less urine protein than control rats. The drug reduced proteinuria in Dahl S rats on high salt diet, but had no significant effect on proteinuria in other groups. In summary, fenofibrate reduced blood pressure and weight gain, increased UVol and PRA, and reduced urine protein excretion in young SHRSP. Other groups of animals showed these changes to a variable, but directionally similar extent. These findings are consistent with a natriuretic effect of fenofibrate. Key words: hypertension, animal models, natriuresis, fenfibrate, lipid lowering agents.

Effects of hypertension and aging on fibronectin expression in aorta of Dahl salt-sensitive rats

1994 ◽  
Vol 267 (4) ◽  
pp. H1523-H1529
Author(s):  
I. Takasaki ◽  
T. Takizawa ◽  
K. Sugimoto ◽  
E. Gotoh ◽  
H. Shionoiri ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mrna Levels ◽  
High Salt Diet ◽  
Salt Loading ◽  
Salt Diet ◽  
Factors Associated ◽  
Severe Stage ◽  
Fibronectin Expression ◽  
Low Salt ◽  
Fibronectin Mrna

Effects of hypertension and aging on aortic fibronectin expression were investigated in male Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats fed either a low- or high-salt diet from 5 to 37 wk of age. In comparison to low-salt controls, the steady-state mRNA levels for aortic fibronectin in salt-loaded Dahl-S rats were dramatically increased at 37 wk of age, corresponding to a severe stage of hypertension with high mortality, whereas at earlier ages representing early to established phases of hypertension, no significant changes were observed. Salt loading affected neither blood pressure nor aortic fibronectin expression in Dahl-R rats. Aging without coexisting hypertension did not cause significant changes in aortic fibronectin mRNA levels all through the study period in either strain of rats. These results suggest that aortic fibronectin may be strongly regulated by factors associated with severe hypertensive organ damages caused by long-standing hypertension in salt-loaded Dahl-S rats. Also suggested was that aortic fibronectin may not play a major role in the pathogenesis of early aortic changes occurring in response to hypertension or as a process of aging.

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