Abstract 302: SHR Animals Have ADH Induced Over Stimulation On Sodium Transport

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Guillermo B Silva ◽  
Luis I Juncos ◽  
Nestor H Garcia
Keyword(s):  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Na Transport ◽  
Positive Balance ◽  
Initial Decrease ◽  
Baseline Values ◽  
Camp Levels ◽  
Superoxide Scavenger

During hypertension kidney fails to maintain Na balance, leading to increased blood volume and blood pressure. It has been suggested that humoral defects and in the last decade in Na transport disorders have been described in different tubular segments. Our aim was to investigate the interaction between antidiuretic hormone (ADH) and angiotensin II (Ang II) in oxygen consumption (QO2, as a marker of Na transport ) in the loop of Henle , in normotensive and hypertensive animals. To do that we used suspensions of thick ascending limbs of the loop of Henle and and measured QO2, cAMP and superoxide production. We found that In normotensive animals, the basal QO2 was 112 ± 5 nmol O2/min/mg protein. ADH (1 nM) increased QO2 227% compared to baseline values. In the presence of ADH and Ang II (1 nM) initially decreased QO2 with a subsequent recovery (279 ± 17 nmol O2/min/mg protein). ADH increased cAMP levels, whereas Ang II decreased it. In contratst, ADH caused no effect in superoxide levels in thick ascending limbs of normotensive and increased after 3.3 minutes incubation. In hypertensive rats, the QO2 was stimulated by 98% after ADH. In these rats, and Ang II + ADH produced an initial decrease QO2 and a subsequent over-stimulation by ADH (184 % increase , p <0.05 vs normotensive animals) . Unlike what was observed in normotensive animals, Ang II increased early superoxide levels before at 1.7 minutes incubation and reached significant values compared to basal. In addition Losartan blocked the Ang II -induced effects. The superoxide scavenger tempol blocked the increase in Ang II -induced QO2 in both animal models. Taken together these results indicate that in hypertensive animals there is an additive effect between ADH and Ang II in the thick ascending limb of the loop of Henle. Therefore, the abnormal mechanism observed in hypertensive animals could explain the Na positive balance in this model of arterial hypertension.

scholarly journals Tyrosine Kinase and Mitogen-Activated Protein Kinase/Extracellularly Regulated Kinase Differentially Regulate Intracellular Calcium Concentration Responses to Angiotensin II/III and Bradykinin in Rat Cortical Thick Ascending Limb

Endocrinology ◽  
2006 ◽  
Vol 147 (1) ◽  
pp. 451-463 ◽  
Author(s):  
Annette Hus-Citharel ◽  
Xavier Iturrioz ◽  
Pierre Corvol ◽  
Jeannine Marchetti ◽  
Catherine Llorens-Cortes
Keyword(s):  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Intracellular Calcium ◽  
Calcium Concentration ◽  
Receptor Type ◽  
Intracellular Calcium Concentration ◽  
Thick Ascending Limb ◽  
Ang Ii ◽  
Na Transport ◽  
Herbimycin A

The cortical thick ascending limb (CTAL) coexpresses angiotensin (Ang) II/Ang III receptor type 1A (AT1A-R) and bradykinin (BK) receptor type 2 (B2-R). In several cell types, these two receptors share the same signaling pathways, although their physiological functions are often opposite. In CTAL, little is known about the intracellular transduction events leading to the final physiological response induced by these two peptides. We investigated and compared in this segment the action of Ang II/III and BK on intracellular calcium concentration ([Ca2+]i) response and metabolic CO2 production, an index of Na+ transport, by using inhibitors of protein kinase C (bisindolylmaleimide), Src tyrosine kinase (herbimycin A and PP2), and MAPK/ERK (PD98059 and UO126). Ang II/III and BK (10−7 mol/liter) released Ca2+ from the same intracellular pools but activated different Ca2+ entry pathways. Ang II/III- or BK-induced [Ca2+]i increases were similarly potentiated by bisindolylmaleimide. Herbimycin A and PP2 decreased similarly the [Ca2+]i responses induced by Ang II/III and BK. In contrast, PD98059 and UO126 affected the effects of BK to a larger extent than those of Ang II/III. Especially, the Ca2+ influx induced by BK was more strongly inhibited than that induced by Ang II/III in the presence of both compounds. The Na+ transport was inhibited by BK and stimulated by Ang II/III. The inhibitory action of BK on Na+ transport was blocked by UO126, whereas the stimulatory response of Ang II/III was potentiated by UO126 but blocked by bisindolylmaleimide. These data suggest that the inhibitory effect of BK on Na+ transport seems to be directly mediated by an increase in Ca2+ influx dependent on MAPK/ERK pathway activation. In contrast, the stimulatory effect of Ang II/III on Na+ transport is more complex and involves PKC and MAPK/ERK pathways.

Oxidant stress in kidneys of spontaneously hypertensive rats involves both oxidase overexpression and loss of extracellular superoxide dismutase

2004 ◽  
Vol 287 (5) ◽  
pp. F907-F913 ◽  
Author(s):  
S. Adler ◽  
H. Huang
Keyword(s):  
Oxygen Consumption ◽  
Spontaneously Hypertensive Rats ◽  
Oxidant Stress ◽  
Superoxide Production ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Renal Oxygen Consumption ◽  
Enhanced Expression ◽  
Superoxide Scavenger

Oxidant stress is an important contributor to renal dysfunction and hypertension. We have previously demonstrated that regulation of renal oxygen consumption by nitric oxide (NO) is impaired in the kidney of spontaneously hypertensive rats (SHR) due to increased superoxide production. We further explored the mechanisms of enhanced oxidant stress in the kidney of SHR. Suppression of cortical oxygen consumption by bradykinin (BK) or enalaprilat (Enal), which act through stimulation of endogenous NO, was impaired in SHR (BK: −14.1 ± 1.2%; Enal: −15.5 ± 1.2%) and was restored by addition of apocynin, an inhibitor of assembly of the NAD(P)H oxidase complex (BK: −21.0 ± 0.6%; Enal: −25.3 ± 1.4%), suggesting this as the source of enhanced superoxide production. Addition of an angiotensin type 1 receptor blocker, losartan, also restored responsiveness to control levels (BK: −22.0 ± 1.1%; Enal: −23.6 ± 1.3%), suggesting that ANG II is responsible for enhanced oxidase activity. A similar defect in responsiveness to BK and Enal could be induced in Wistar-Kyoto kidneys by ANG II and was reversed by a superoxide scavenger (tempol), apocynin or losartan. Immunoblotting of cortical samples demonstrated enhanced expression of endothelial NO synthase (eNOS 1.9×) and NAD(P)H oxidase components (gp91 phox 1.6× and Rac-1 4.5×). Expression of SOD-1 and -2 were unchanged, but SOD-3 was significantly decreased in SHR (0.5×). Thus NO bioavailability is impaired in SHR owing to an ANG II-mediated increase in superoxide production in association with enhanced expression of NAD(P)H oxidase components, despite increased expression of eNOS. Loss of SOD-3, an important superoxide scavenger, may also contribute to enhanced oxidant stress.

Effects of dietary Ca2+ on erythrocyte Na+-transport systems in spontaneously hypertensive rats

1991 ◽  
Vol 81 (1) ◽  
pp. 107-112 ◽  
Author(s):  
K. Fujito ◽  
M. Yokomatsu ◽  
N. Ishiguro ◽  
H. Numahata ◽  
Y. Tomino ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Transport Systems ◽  
Hypertensive Rats ◽  
Na Transport ◽  
Spontaneously Hypertensive ◽  
Na Pump ◽  
Wistar Kyoto ◽  
Increased Activity ◽  
Regulation Of Blood Pressure

1. The purpose of this study was to determine the effect of dietary Ca2+ intake on blood pressure and erythrocyte Na+ transport in spontaneously hypertensive rats. 2. Spontaneously hypertensive rats and Wistar-Kyoto rats were fed diets with three different Ca2+ contents, 0.1% (low-Ca2+ diet), 0.6% (normal-Ca2+ diet) and 4.0% (high-Ca2+ diet), between 6 and 20 weeks of age. At 20 weeks of age, the levels of erythrocyte Na+ efflux, as well as Na+ and K+ contents in erythrocytes, were measured. 3. On the low-Ca2+ diet, spontaneously hypertensive rats showed an enhancement of hypertension. Conversely, on the high-Ca2+ diet, they showed an attenuation of the increase in blood pressure. Spontaneously hypertensive rats had a lower erythrocyte Na+ content and increased activity of the Na+ pump at higher levels of dietary Ca2+. Passive Na+ permeability and Na+-K+ co-transport were similar in spontaneously hypertensive rats on the low-, normal- and high-Ca2+ diets. There were no significant differences in blood pressure and in Na+ pump activity in WKY on the three different diets. 4. It is concluded that dietary Ca2+ might affect the regulation of blood pressure in spontaneously hypertensive rats by changing the activity of Na+ pump in the cell membrane.

Abstract P059: A A Role of Aminopeptidase A in the Brain on Cardiovascular Regulation of Conscious Rat

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Takuto Nakamura ◽  
Masanobu Yamazato ◽  
Akio Ishida ◽  
Yusuke Ohya
Keyword(s):  
Blood Pressure ◽  
Protein Expression ◽  
Drinking Behavior ◽  
Cardiovascular Regulation ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Aminopeptidase A ◽  
The Brain

Objective: Aminopeptidase A (APA) have important role in conversion of Ang II to Ang III. Intravenous APA administration lowers blood pressure in hypertensive rats. In contrast, APA inhibition in the brain lowers blood pressure in hypertensive rats. Therefore APA might have different role on cardiovascular regulation. However, a role of APA and Ang III on cardiovascular regulation especially in the brain has not been fully understood. Our purpose of present study was to investigate a role of APA and Ang III in the brain on cardiovascular regulation in conscious state. Method: 12-13 weeks old Wistar Kyoto rat (WKY) and 12-16 weeks old spontaneously hypertensive rat (SHR) were used. i) APA distribution in the brain was evaluated by immunohistochemistry. Protein expression of APA was evaluated by Western blotting. Enzymatic activity of APA was evaluated using L-glutamic acid γ-(4-nitroanilide) as a substrate. ii) WKY received icv administration of Ang II 25ng/2μL and Ang III 25ng/2μL. We recorded change in mean arterial pressure (MAP) in conscious and unrestraied state and measured induced drinking time. iii) SHR received icv administeration of recombinant APA 400ng/4μL. We recorded change in MAP in conscious and unrestraied state and measured induced drinking time. Result: i) APA was diffusely immunostained in the cells of brain stem including cardiovascular regulatory area such as rostral ventrolateral medulla. Protein expression and APA activity in the brain were similar between WKY (n=3) and SHR (n=3).ii) Icv administration of Ang II increased MAP by 33.8±3.8 mmHg and induced drinking behavior for 405±90 seconds (n=4). Icv administration of Ang III also increased MAP by 24.7±2.4 mmHg and induced drinking behavior for 258±62 seconds (n=3). These vasopressor activity and induced drinking behavior was completely blocked by pretretment of angiotensin receptor type 1 blocker.iii) Icv administration of APA increased MAP by 10.0±1.7 mmHg (n=3). Conclusion: These results suggested that Ang III in the brain increase blood pressure by Angiotensin type 1 receptor dependent mechanism and APA in the brain may involved in blood pressure regulation as a vasopressor enzyme.

DARPP-32 promoter directs transgene expression to renal thick ascending limb of loop of Henle

1995 ◽  
Vol 269 (4) ◽  
pp. F564-F570 ◽  
Author(s):  
S. Blau ◽  
L. Daly ◽  
A. Fienberg ◽  
G. Teitelman ◽  
M. E. Ehrlich
Keyword(s):  
Transgene Expression ◽  
Ectopic Expression ◽  
Medium Size ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Transcription Start Sites ◽  
Medullary Thick Ascending Limb ◽  
Spiny Neurons ◽  
Adult Kidney ◽  
The Brain

DARPP-32, a dopamine- and adenosine 3',5'-cyclic monophosphate (cAMP)-regulated inhibitor of protein phosphatase-1, is highly colocalized with neuronal and nonneuronal D1-type receptors. DARPP-32 concentration is enriched in the renal outer medulla and in the medium-size spiny neurons of the brain. In the ascending limb of the loop of Henle, DARPP-32 is phosphorylated following stimulation by dopamine and other first messengers, and in this form inhibits the activity of the Na(+)-K(+)-adenosinetriphosphatase pump. For functional analysis of the DARPP-32 promoter in the kidney, we characterized the murine gene. There are two groups of transcription start sites utilized in the brain, but the proximal set appears to be preferentially used in the kidney. In four of four lines of mice carrying a DARPP-32/lacZ transgene with 2.1 kb of 5'-flanking DNA, adult kidney lacZ transgene expression mimicked that of endogenous DARPP-32. There was no ectopic expression in peripheral organs. We conclude that the sequences necessary for direction of DARPP-32 expression to the medullary thick ascending limb are contained within this 2.1-kb fragment.

ANG II controls Na+-K+( NH 4 + )-2Cl−cotransport via 20-HETE and PKC in medullary thick ascending limb

1998 ◽  
Vol 274 (4) ◽  
pp. C1047-C1056 ◽  
Author(s):  
Hassane Amlal ◽  
Christian LeGoff ◽  
Catherine Vernimmen ◽  
Manoocher Soleimani ◽  
Michel Paillard ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Thick Ascending Limb ◽  
Ang Ii ◽  
Diacylglycerol Lipase ◽  
Medullary Thick Ascending Limb ◽  
Kinase C ◽  
Cell Ph ◽  
Cytochrome P 450

Cell pH was monitored in medullary thick ascending limbs to determine effects of ANG II on Na+-K+([Formula: see text])-2Cl−cotransport. ANG II at 10−16to 10−12 M inhibited 30–50% ( P < 0.005), but higher ANG II concentrations were stimulatory compared with the 10−12 M ANG II level cotransport activity; eventually, 10−6 M ANG II stimulated 34% cotransport activity ( P < 0.003). Inhibition by 10−12M ANG II was abolished by phospholipase C (PLC), diacylglycerol lipase, or cytochrome P-450-dependent monooxygenase blockade; 10−12 M ANG II had no effect additive to inhibition by 20-hydroxyeicosatetranoic acid (20-HETE). Stimulation by 10−6 M ANG II was abolished by PLC and protein kinase C (PKC) blockade and was partially suppressed when the rise in cytosolic Ca2+ was prevented. All ANG II effects were abolished by DUP-753 (losartan) but not by PD-123319. Thus ≤10−12 M ANG II inhibits via 20-HETE, whereas ≥5 × 10−11 M ANG II stimulates via PKC Na+-K+([Formula: see text])-2Cl−cotransport; all ANG II effects involve AT1 receptors and PLC activation.

Low Na intake suppresses expression of CYP2C23 and arachidonic acid-induced inhibition of ENaC

2006 ◽  
Vol 291 (6) ◽  
pp. F1192-F1200 ◽  
Author(s):  
Peng Sun ◽  
Dao-Hong Lin ◽  
Tong Wang ◽  
Elisa Babilonia ◽  
Zhijian Wang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Collecting Duct ◽  
Inhibitory Effect ◽  
Thick Ascending Limb ◽  
Epoxyeicosatrienoic Acid ◽  
Distal Nephron ◽  
Na Transport ◽  
Deficient Diet ◽  
Epithelial Na Channels ◽  
Clamp Study

We previously demonstrated that arachidonic acid (AA) inhibits epithelial Na channels (ENaC) through the cytochrome P-450 (CYP) epoxygenase-dependent pathway ( 34 ). In the present study, we tested the hypothesis that low Na intake suppresses the expression of CYP2C23, which is mainly responsible for converting AA to epoxyeicosatrienoic acid (EET) in the kidney ( 11 ) and attenuates the AA-induced inhibition of ENaC. Immunostaining showed that CYP2C23 is expressed in the Tamm-Horsfall protein (THP)-positive and aquaporin 2 (AQP2)-positive tubules. This suggests that CYP2C23 is expressed in the thick ascending limb (TAL) and collecting duct (CD). Na restriction significantly suppressed the expression of CYP2C23 in the TAL and CD. Western blot also demonstrated that the expression of CYP2C23 in renal cortex and outer medulla diminished in rats on Na-deficient diet (Na-D) but increased in those on high-Na diet (4%). Moreover, the content of 11,12-epoxyeicosatrienoic acid (EET) decreased in the isolated cortical CD from rats on Na-D compared with those on a normal-Na diet (0.5%). Patch-clamp study showed that application of 15 μM AA inhibited the activity of ENaC by 77% in the CCD of rats on a Na-D for 3 days. However, the inhibitory effect of AA on ENaC was significantly attenuated in rats on Na-D for 14 days. Furthermore, inhibition of CYP epoxygenase with MS-PPOH increased the ENaC activity in the CCD of rats on a control Na diet. We also used microperfusion technique to examine the effect of MS-PPOH on Na transport in the distal nephron. Application of MS-PPOH significantly increased Na absorption in the distal nephron of control rats but had no significant effect on Na absorption in rats on Na-D for 14 days. We conclude that low Na intake downregulates the activity and expression of CYP2C23 and attenuates the inhibitory effect of AA on Na transport.

Upregulation of juxtaglomerular NOS1 and COX-2 precedes glomerulosclerosis in fawn-hooded hypertensive rats

2001 ◽  
Vol 280 (4) ◽  
pp. F706-F714 ◽  
Author(s):  
Wilko Weichert ◽  
Alexander Paliege ◽  
Abraham P. Provoost ◽  
Sebastian Bachmann
Keyword(s):  
Smooth Muscle Actin ◽  
Age Groups ◽  
Juxtaglomerular Apparatus ◽  
Thick Ascending Limb ◽  
Hypertensive Rats ◽  
Renin Mrna ◽  
The Media ◽  
Cox 2 ◽  
Nitric Oxide Synthase 1 ◽  
Oxide Synthase

This study describes elevated histochemical signals for nitric oxide synthase-1 (NOS1) and cyclooxygenase-2 (COX-2) in juxtaglomerular apparatus (JGA) and adjacent thick ascending limb of the kidney of fawn-hooded hypertensive rats (FHH). Two different age groups of FHH (8 and 16 wk; FHH8 and FHH16, respectively) were compared with genetically related fawn-hooded rats with normal blood pressure (FHL) that served as controls. Histopathological changes in FHH comprised focal segmental glomerulosclerosis (FSGS), focal matrix overexpression, and a moderate arteriolopathy with hypertrophy of the media, enhanced immunoreactivity for α-smooth muscle actin, and altered distribution of myofibrils. Macula densa NOS activity, as expressed by NADPH-diaphorase staining, and NOS1 mRNA abundance were significantly elevated in FHH8 (+153 and +88%; P < 0.05) and FHH16 (+93 and +98%; P < 0.05), respectively. Even higher elevations were registered for COX-2 immunoreactivity in FHH8 (+166%; P < 0.05) and FHH16 (+157%; P < 0.05). The intensity of renin immunoreactivity and renin mRNA expression in afferent arterioles was also elevated in FHH8 (+51 and +166%; P < 0.05) and FHH16 (+105 and +136%; P < 0.05), respectively. Thus we show that coordinate upregulation of tubular NOS1, COX-2, and renin expression precedes, and continues after, the manifestation of glomerulosclerotic damage in FHH. These observations may have implications in understanding the role of local paracrine mediators in glomerular disease.

scholarly journals More actors in ammonia absorption by the thick ascending limb

2012 ◽  
Vol 302 (3) ◽  
pp. F293-F297 ◽  
Author(s):  
Pascal Houillier ◽  
Soline Bourgeois
Keyword(s):  
Current Knowledge ◽  
Collecting Duct ◽  
Ammonia Excretion ◽  
Hydrogen Ion ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Transport Mechanisms ◽  
Sodium Hydrogen ◽  
Ammonia Transport ◽  
Ammonia Absorption

This review will briefly summarize current knowledge on the basolateral ammonia transport mechanisms in the thick ascending limb (TAL) of the loop of Henle. This segment transports ammonia against a concentration gradient and is responsible for the accumulation of ammonia in the medullary interstitium, which, in turn, favors ammonia secretion across the collecting duct. Experimental data indicate that the sodium/hydrogen ion exchanger isoform 4 (NHE4; Scl9a4) is a sodium/ammonia exchanger and plays a major role in this process. Disruption of murine NHE4 leads to metabolic acidosis with inappropriate urinary ammonia excretion and decreases the ability of the TAL to absorb ammonia and to build the corticopapillary ammonia gradient. However, NHE4 does not account for the entirety of ammonia absorption by the TAL, indicating that, at least, one more transporter is involved.

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