Abstract P335: Greater Reduction in Sympathetic Tone following ET B Receptor Blockade in Rats Lacking the Clock Gene Bmal1 during High Salt Diet

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Jermaine G Johnston ◽  
Bryan K Becker ◽  
Chunhua Jin ◽  
David M Pollock
Keyword(s):  
Blood Pressure ◽  
Clock Gene ◽  
Recovery Period ◽  
Sympathetic Tone ◽  
High Salt ◽  
Male Rats ◽  
Receptor Blockade ◽  
High Salt Diet ◽  
Salt Diet ◽  
Cardiovascular Morbidity And Mortality

The absence of diurnal oscillations in blood pressure is associated with increased cardiovascular morbidity and mortality. The clock gene Bmal1 plays important roles in diurnal cardiovascular control as mice lacking Bmal1 have lower blood pressure and lack a diurnal rhythm. Our lab has previously reported a global Bmal1 knockout rat model that lacks a night-day difference in sodium excretion. Due to the importance of endothelin signaling in sodium homeostasis and autonomic tone, we sought to characterize the hemodynamic and autonomic responses of our Bmal1 knockout (KO) rat to high salt diet and endothelin receptor blockade. Male rats homozygous for the Bmal1 mutation (KO, n = 4) and wild type (WT, n = 7) littermate controls were implanted with telemetry transmitters to record blood pressure. After a recovery period of at least one week, the rats were placed on 7 days each of normal salt (0.49% NaCl) diet, high salt (4.0% NaCl) diet, followed by high salt diet containing the specific ET B receptor antagonist A192621 (10 mg/kg/day, p.o.). Rats were placed in metabolic cages for the last three days of each diet. Surprisingly, KO rats had a similar night-day difference in mean arterial pressure (MAP) as WT during normal salt diet (6.3 ± 0.4 vs. 6.9 ± 0.9 mmHg; respectively), high salt diet (7.1 ± 0.1 vs. 5.4 ± 0.9 mmHg; respectively), and high salt + A192621 (5.4 ± 0.4 vs. 4.8 ± 1.1 mmHg; respectively). KO and WT rats had similar 24-hr MAP during normal salt diet (104.1 ± 3.3 vs. 107.3 ± 1.2 mmHg; respectively), high salt diet (113.8 ± 4.1 vs. 114.0 ± 1.4 mmHg; respectively), and high salt + A192621 (136.3 ± 8.6 vs. 133.4 ± 3.1 mmHg; respectively). Despite these similar blood pressure responses to high salt diet and ET B antagonism, KO rats had a significantly greater reduction in vasomotor sympathetic to parasympathetic tone compared to WT rats as demonstrated by low frequency to high frequency (LF/HF) analysis of diastolic blood pressure variability (-0.9 ± 0.3 vs. 0.1 ± 0.2 ΔLF/HF relative to normal salt; respectively; p = 0.01). These results indicate that lack of Bmal1 may result in greater ET B receptor mediated vasomotor sympathetic tone in rats fed a high salt diet and that factors other than Bmal1 may be influential in circadian control of blood pressure in rats.

Abstract 096: Leptin and High Salt Diet Induce Greater Increases in Blood Pressure in Female than Male Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Jessica L Faulkner ◽  
Eric J Belin de Chantemele
Keyword(s):  
Blood Pressure ◽  
Recovery Period ◽  
Pressure Rise ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Male And Female ◽  
Female Mice ◽  
Males And Females ◽  
Blood Pressure Responses

Recent studies by our group demonstrated that leptin is a direct regulator of aldosterone secretion and increases blood pressure via sex-specific mechanisms involving leptin-mediated activation of the aldosterone-mineralocorticoid receptor signaling pathway in females and sympatho-activation in males. Although it is well accepted that females secrete more leptin and aldosterone than males, it is unknown whether leptin infusion raises blood pressure similarly in male and female mice and whether higher aldosterone levels sensitize females to salt-induced hypertension. We hypothesized that female mice would be more sensitive to leptin than males and also have a potentiated blood pressure rise in response to high salt diet compared to males. Male and female Balb/C mice were implanted with radiotelemeters for continuous measurement of mean arterial pressure (MAP) at 10 weeks of age. MAP was measured for seven days prior to feeding with a high-salt diet (HS, 4%NaCl) for seven days. Following a recovery period, animals were then implanted with osmotic minipumps containing leptin (0.9mg/kg/day) recorded for seven days. Baseline MAP was similar between males and females (101.3±2.9 vs 99.3±3.7 mmHg, n=4 and 5, respectively), however, HS diet resulted in a greater MAP increase in females (15.0±2.6 mmHg) compared to males (3.1±4.5 mmHg, P<0.05). MAP with leptin treatment was increased with leptin in females moreso than in males, however, this did not reach significance (6.8±5.8 vs 1.8±5.9 mmHg, respectively). This potential sex difference in blood pressure responses to leptin was not associated with changes in body weight (0.07±0.44 vs -0.22±0.2 g, respectively) nor changes in blood glucose (-19.67±15.06 vs -15.4±11.4 mg/dl, respectively) in males and females in response to leptin. In summary, female mice are more sensitive to HS diet-induced blood pressure increases than males. Females may be more sensitive to leptin-mediated blood pressure increases than males. Further investigation is needed to determine whether these sex differences in blood pressure responses to HS diet and leptin are mediated by aldosterone or other mechanisms.

Multiple blood pressure loci on rat chromosome 13 attenuate development of hypertension in the Dahl S hypertensive rat

2007 ◽  
Vol 31 (2) ◽  
pp. 228-235 ◽  
Author(s):  
Carol Moreno ◽  
Mary L. Kaldunski ◽  
Tao Wang ◽  
Richard J. Roman ◽  
Andrew S. Greene ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Damage ◽  
High Salt ◽  
Male Rats ◽  
Brown Norway ◽  
High Salt Diet ◽  
Salt Diet ◽  
Chromosome 13 ◽  
Congenic Strains ◽  
Multiple Blood

Previous studies have indicated that substitution of chromosome 13 of the salt-resistant Brown Norway BN/SsNHsdMcwi (BN) rat into the genomic background of the Dahl salt-sensitive SS/JrHsdMcwi (SS) rat attenuates the development of salt-sensitive hypertension and renal damage. To identify the regions within chromosome 13 that attenuate the development of hypertension during a high-salt diet in the SS rat, we phenotyped a series of overlapping congenic lines covering chromosome 13, generated from an intercross between the consomic SS-13BN rat and the SS rat. Blood pressure was determined in chronically catheterized rats after 2 wk of high-salt diet (8% NaCl) together with microalbuminuria as an index of renal damage. Four discrete regions were identified, ranging in size from 4.5 to 16 Mbp, each of which independently provided significant protection from hypertension during high-salt diet, reducing blood pressure by 20–29 mmHg. Protection was more robust in female than male rats in some of the congenic strains, suggesting a sex interaction with some of the genes determining blood pressure during high-salt diet. Among the 23 congenic strains, several regions overlapped. When three of the “protective” regions were combined onto one broad congenic strain, no summation effect was seen, obtaining the same decrease in blood pressure as with each one independently. We conclude from these studies that there are four regions within chromosome 13 containing genes that interact epistatically and influence arterial pressure.

Abstract P149: Bilateral Renal Denervation Attenuates Hypertension in Male Rats Deficient of Functional Endothelin B Receptors but Does Not Affect Salt-Sensitivity

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Bryan K Becker ◽  
Amanda C Feagans ◽  
Chunhua Jin ◽  
David M Pollock
Keyword(s):  
Blood Pressure ◽  
Total Protein ◽  
Renal Denervation ◽  
High Salt ◽  
Male Rats ◽  
Renal Nerves ◽  
High Salt Diet ◽  
Salt Diet ◽  
Endothelin B ◽  
Renal Sympathetic

Independent studies of renal sympathetic nerves and the endothelin (ET) system have demonstrated important contributions of each in the progression of hypertension. Very few studies, however, have investigated the interaction between the ET system and renal nerves in relation to blood pressure control and electrolyte homeostasis. Although endothelin B (ETB) receptors in the renal medulla promote natriuresis, ETB receptors on sympathetic neurons are thought to increase neuronal activity. We hypothesized that renal denervation reduces blood pressure in a salt-sensitive, hypertensive model of ET dysfunction, the ETB-deficient (ETB-def) rat, which lacks functional ETB receptors in all tissues except neurons. After bilateral renal sympathetic denervation (Dnx) or sham operation of ETB-def and transgenic control (TG) rats, baseline blood pressure was recorded via telemetry for 5 days on a normal salt (0.49% NaCl) diet followed by a high salt (4.0%) diet. At baseline, ETB-def Dnx rats had a lower 24-hr systolic blood pressure (SBP) (152.6 ± 3.6 mmHg) relative to ETB-def sham (167.8 ± 2.6 mmHg; p < 0.005; n = 7/group). Denervation did not significantly affect TG rats relative to sham on normal salt (138.8 ± 2.5 vs. 144.7 ± 0.5 mmHg respectively; p = 0.53; n = 6/group). Following 10 days of high salt diet, ETB-def sham rats had an increased 24-hr SBP (+10.59 ± 2.8 mmHg relative to baseline; p < 0.005). There was a similar increase in SBP in ETB-def Dnx rats (+10.03 ± 2.3 mmHg relative to baseline; p < 0.005), although the ETB-def Dnx group remained lower than ETB-def sham. High salt had no effect on TG sham or Dnx animals (-2.2 ± 1.3 and -0.6 ± 2.8 mmHg relative to baseline). Preliminary evidence from a subset of the animals in this experiment indicated a dramatically reduced inner medullary ET-1 content in ETB-def sham rats vs. TG sham (97.9 ± 15.4 vs. 327.0 ± 25.4 ng/mg total protein; p < 0.005; n = 3-4/group) in both ETB-def and TG groups, Dnx tended to increase inner medullary ET-1 content (181.8 ± 75.8 and 402.7 ± 19.6 ng/mg total protein respectively). We conclude that in a model of ET dysfunction, the renal nerves are integral mediators of hypertension during normal salt diet, but do not mediate the increase in pressure following high salt diet in this model of salt-sensitive hypertension.

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.

scholarly journals Gambaran Tekanan Darah Tikus Wistar Jantan dan Betina Setelah Pemberian Diet Tinggi Garam

2013 ◽  
Vol 2 (3) ◽  
pp. 146
Author(s):  
Mutia Lailani ◽  
Zulkarnain Edward ◽  
Rahmatina B Herman
Keyword(s):  
Blood Pressure ◽  
High Salt ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
Control Group Design ◽  
High Salt Diet ◽  
Salt Diet ◽  
Group Design ◽  
Post Test

AbstrakHipertensi masih menjadi masalah kesehatan di dunia. Penyebabnya diduga berkaitan dengan diet tinggi garam. Tujuan Penelitian ini ialah untuk mengetahui gambaran tekanan darah tikus Wistar setelah pemberian diet tinggigaram. Penelitian ini adalah eksperimental dengan post-test only control group design. Subjek penelitian terdiri dari 10 ekor tikus Wistar jantan dan 10 ekor betina yang dibagi menjadi kelompok kontrol (K) dan kelompok perlakuan (P). Diet tinggi garam (NaCl8%, 3ml/hari) diberikan pada kelompok P selama empat minggu. Hasil penelitian menunjukkan bahwa terjadi peningkatan tekanan darah yang bermakna pada kelompok P bila dibandingkan dengan kelompok K, yaitu tekanan darah sistolik (TDS) 191±17mmHg (P) dan 168±16mmHg (K) (p<0,05), tekanan darah diastolik (TDD) 162±17mmHg (P) dan 139±13mmHg (K) (p<0,05), tekanan arteri rata-rata (TAR) 176±17mmHg (P) dan 156±15mmHg (K) (p<0,05). Peningkatan TDS dan TDD hanya terjadi pada tikus jantan, tidak pada tikus betina. Pada tikus jantan TDS 185±13mmHg (P) dan 159±9mmHg (K) (p<0,05), TDD 159±18mmHg (P) dan 131±10mmHg (K) (p<0,05), TAR 172±16mmHg (P) dan 150±15mmHg (K) (p>0,05). Pada tikus betina TDS 197±19mmHg (P) dan 178±16mmHg (K) (p>0,05), TDD 165±18mmHg (P) dan 148±11mmHg (K) (p>0,05), TAR 181±18mmHg (P) dan 162±14mmHg (K) (p>0,05). Kesimpulan studi ini adalah peningkatan tekanan darah setelah pemberian diet tinggi garam hanya terjadi pada tikus jantan.Kata kunci: diet tinggi garam, tekanan darah, hipertensiAbstractHypertension remains a health problem in the world. The cause is believed to be related to the high-salt diet. The purpose of this studi was to describe the blood pressure of Wistar rats after administration of high-salt diet. This research was experimental with post-test only control group design. Ten male and ten female Wistar rats were divided into two groups: control group(K) and treated group(P). High-salt diet (8%NaCl, 3ml/day) was given to the P group for four weeks. Blood pressure increased significantly in group P compared to group K, systolic blood pressure (SBP) 191±17mmHg (P) and 168±16mmHg (K) in (p<0.05), diastolic blood pressure (DBP) 162±17mmHg (P) and 139±13mmHg (K) in (p<0.05), mean arterial pressure (MAP) 176±17mmHg (P) and 156±15mmHg (K) in (p<0.05). The increase in SBP and DBP only occurred in male rats, not in female rats. In male rats, SBP were 185±13mmHg (P) and 159±9mmHg (K) in (p<0.05), DBP were 159±18mmHg (P) and 131±10mmHg (K) in (p<0.05), MAP were 172±16mmHg (P) and 150±15mmHg (K) in (p>0.05). In female rats, SBP were197±19mmHg (P) and 178±16mmHg (K) in (p>0.05), DBP were 165±18mmHg (P) and 148±11mmHg (K) in (p>0.05), MAP were 181±18mmHg (P) and 162±14mmHg (K) in (p>0.05). The conclusion of this study is an increase of blood pressure after the administration of high-salt diet only occured in male rats.Keywords: high-salt diet, blood pressure, hypertension

Abstract 160: Characterization of a Comt Knock-out Rat for Blood Pressure and Associated Phenotypes.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Marc Casati ◽  
Mathew Hoffman ◽  
Rebecca Schilling ◽  
Michael Flister ◽  
Aron M Geurts ◽  
...  
Keyword(s):  
Blood Pressure ◽  
High Salt ◽  
Male Rats ◽  
Zinc Finger Nucleases ◽  
Dependent Manner ◽  
Electrolyte Excretion ◽  
High Salt Diet ◽  
Salt Diet ◽  
Low Salt ◽  
Salt Sensitive Hypertension

The catecholamine system plays an important role in the control of blood pressure and sodium excretion. One of the inactivation pathways of catecholamines is the enzymatic metabolism by catechol-O-methyltransferase (Comt). There are conflicting data regarding the role of Comt on the development of salt-sensitive hypertension, so the goal of our study was to evaluate the importance of Comt in the context of a susceptible background in vivo. Comt was mutated in the Dahl SS rat by zinc finger nucleases (ZFNs) injections targeting the sequence CTGTTCCAGGTCACCATCctcaatGGGGCATCCCAGGATCTT into SS/JrHsdMcwi (Dahl S) rat embryos. The resulting mutation was a 14-bp frameshift deletion in exon 4. Conscious blood pressure was measured by telemetry on male and female Comt knockout and wild type (WT) rats on low salt diet (0.4% NaCl) and during three weeks of high salt diet (8%NaCl). Disruption of Comt caused the protein not to express in the kidneys of the Dahl S rat. There were no differences in mean arterial pressure (MAP) between the Comt -/- and the Comt +/+ male rats at any time point during the day-night cycle at low or high salt diet. Body and organ weights, and protein and electrolyte excretion was also unchanged by the Comt mutation. On the other hand, female Comt -/- rats evidenced a higher MAP, which was only significantly higher at night during low salt diet (112±2 mmHg in Comt +/+ vs 125±2 mmHg in the Comt -/-, n>6) and both during day and night after 21 days of high-salt diet (∼ 30 mmHg difference between Comt +/+ and Comt -/- strains at both day and night). Systolic blood pressure differences were mostly responsible for the observed blood pressure diferences in females KO of the Comt gene, despite blood pressure effect, was not followed by a parallel difference in urine flow, electrolyte excretion or renal damage (protein and albumin excretion). In conclusion, we are the first ones to show that disruption of Comt enhances salt-sensitive hypertension in a gender-dependent manner.

Abstract P267: Sex Differences in Cyp450 Activity and the Development of Hypertension and Renal Injury in the Dahl S Rat

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Wenjie Wu ◽  
Sydney Murphy
Keyword(s):  
Blood Pressure ◽  
Renal Injury ◽  
High Salt ◽  
Female Rats ◽  
Male Rats ◽  
High Salt Diet ◽  
Salt Diet ◽  
Renal Vessels ◽  
Female Relative ◽  
Renal Vascular

It is well documented that a sexual dimorphism exists in the regulation of blood pressure in both the human population as well as experimental animal models, however evidence of a sex difference is lacking in the Dahl S rat. Thus, we hypothesize that alterations in CYP450 expression and 20-HETE production contribute to the progression of renal injury in Dahl S rats. Consistent with what we have previously reported, no difference was noted in the blood pressure of male or female Dahl SSJr rat (213.8±12 vs 196.8±13 mmHg, ns) following 4 weeks of a high salt diet (8%NaCl). However, proteinuria (148±25 vs 355±22 mg/day, p<0.05) and renal injury (1.9±0.01 vs 2.5±0.2) were lower in female relative to male rats. In addition, GFR was significantly reduced in male vs female rats (392.4±89 vs 829.5±98 μl/min/g, p<0.05) following at high salt challenge. Renal cortical (11.3.8±16 vs 20.99±2.8 pmol/min/mg, p<0.05) and outer medullary (19.4±3 vs 6.9±1.8 pmol/min/mg, p<0.05) 20-HETE production was elevated in female versus male rats. Furthermore, renal vascular 20-HETE production was elevated in the renal vessels compared to males (0.53±0.23 vs 3.2±1.2 pmol/min/mg, p<0.05). Thus, alterations in the production of renal eicosanoids may contribute to the delay in renal injury in females relative to male Dahl SSJr rats. AHA 14SDG20160020

scholarly journals Metabolic Syndrome and Salt-Sensitive Hypertension in Polygenic Obese TALLYHO/JngJ Mice: Role of Na/K-ATPase Signaling

2019 ◽  
Vol 20 (14) ◽  
pp. 3495 ◽  
Author(s):  
Yanling Yan ◽  
Jiayan Wang ◽  
Muhammad A. Chaudhry ◽  
Ying Nie ◽  
Shuyan Sun ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Significant Rise ◽  
Protein Carbonylation ◽  
High Salt ◽  
Kidney Cortex ◽  
High Salt Diet ◽  
Salt Diet ◽  
Salt Sensitive Hypertension

We have demonstrated that Na/K-ATPase acts as a receptor for reactive oxygen species (ROS), regulating renal Na+ handling and blood pressure. TALLYHO/JngJ (TH) mice are believed to mimic the state of obesity in humans with a polygenic background of type 2 diabetes. This present work is to investigate the role of Na/K-ATPase signaling in TH mice, focusing on susceptibility to hypertension due to chronic excess salt ingestion. Age-matched male TH and the control C57BL/6J (B6) mice were fed either normal diet or high salt diet (HS: 2, 4, and 8% NaCl) to construct the renal function curve. Na/K-ATPase signaling including c-Src and ERK1/2 phosphorylation, as well as protein carbonylation (a commonly used marker for enhanced ROS production), were assessed in the kidney cortex tissues by Western blot. Urinary and plasma Na+ levels were measured by flame photometry. When compared to B6 mice, TH mice developed salt-sensitive hypertension and responded to a high salt diet with a significant rise in systolic blood pressure indicative of a blunted pressure-natriuresis relationship. These findings were evidenced by a decrease in total and fractional Na+ excretion and a right-shifted renal function curve with a reduced slope. This salt-sensitive hypertension correlated with changes in the Na/K-ATPase signaling. Specifically, Na/K-ATPase signaling was not able to be stimulated by HS due to the activated baseline protein carbonylation, phosphorylation of c-Src and ERK1/2. These findings support the emerging view that Na/K-ATPase signaling contributes to metabolic disease and suggest that malfunction of the Na/K-ATPase signaling may promote the development of salt-sensitive hypertension in obesity. The increased basal level of renal Na/K-ATPase-dependent redox signaling may be responsible for the development of salt-sensitive hypertension in polygenic obese TH mice.

Endothelin B receptors impair baroreflex function and increase blood pressure variability during high salt diet

2021 ◽  
pp. 102796
Author(s):  
Bryan K. Becker ◽  
Jermaine G. Johnston ◽  
Carolyn Young ◽  
Alfredo A. Torres Rodriguez ◽  
Chunhua Jin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Variability ◽  
High Salt ◽  
Increase Blood Pressure ◽  
High Salt Diet ◽  
Salt Diet ◽  
Baroreflex Function ◽  
Endothelin B
Sign in / Sign up

Export Citation Format

Share Document