Abstract 9: Endothelin B Receptors Protect Against Hypertension Induced by Chronic Angiotensin II in Female Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Wararat Kittikulsuth ◽  
David M Pollock

Endothelin B (ET B ) receptors mediate vasodilation, anti-inflammation and natriuresis, which ultimately contribute to blood pressure control. We previously showed that renal medullary ET B receptor function is maintained in female angiotensin (Ang) II hypertensive rats, while male Ang II hypertensive rats have blunted ET B -induced natriuretic responses. Because female rats are more resistance to blood pressure elevation induced by high salt intake and/or Ang II infusion, we hypothesized that ET B receptors protect female rats against the hypertensive response and renal injury induced by a high salt diet and chronic Ang II infusion compared to males. Male and female rats received Ang II infusion (150 ng/kg/min; sc.) with 4% NaCl for 4 weeks; blood pressure was measured by telemetry. After a week of Ang II infusion with a high salt diet, subsets of both male and female rats received the ET B antagonist, A-192621, at three doses on consecutive weeks (1, 3, and 10 mg/kg/d in food). Male rats had a significantly higher blood pressure compared to females after 4 weeks of Ang II (178±10 vs. 138±10 mmHg; p<0.05). A-192621 resulted in a dose-dependent increase in blood pressure in female Ang II hypertensive rats (167±8 mmHg at 10 mg/kg/d; p<0.05); the increase produced by A-192621 in male Ang II hypertensive rats was not statistically significant (193±10 mmHg). After 4 weeks of Ang II infusion, the level of proteinuria and nephrinuria was higher in male rats compared to female. A-192621 did not further increase urinary excretion of protein or nephrin in both male and female Ang II hypertensive rats. In conclusion, these results support the hypothesis that ET B receptors provide more protection against hypertension during chronic Ang II infusion in female rats compared to male.

2020 ◽  
Vol 318 (3) ◽  
pp. R567-R578 ◽  
Author(s):  
Susana Quirós Cognuck ◽  
Wagner L. Reis ◽  
Marcia S. Silva ◽  
Gislaine Almeida-Pereira ◽  
Lucas K. Debarba ◽  
...  

Maintenance of the volume and osmolality of body fluids is important, and the adaptive responses recruited to protect against osmotic stress are crucial for survival. The objective of this work was to compare the responses that occur in aging male and female rats during water deprivation. For this purpose, groups of male and female Wistar rats aged 3 mo (adults) or 18 mo (old) were submitted to water deprivation (WD) for 48 h. The water and sodium (0.15 M NaCl) intake, plasma concentrations of oxytocin (OT), arginine vasopressin (AVP), corticosterone (CORT), atrial natriuretic peptide (ANP), and angiotensin II (ANG II) were determined in hydrated and water-deprived animals. In response to WD, old male and female rats drank less water and saline than adults, and both adult and old females drank more water and saline than respective males. Dehydrated old animals displayed lower ANG II plasma concentration and CORT response compared with the respective normohydrated rats. Dehydrated adult males had higher plasma ANP and AVP as well as lower CORT concentrations than dehydrated adult females. Moreover, plasma OT and CORT levels of old female rats were higher than those in the dehydrated old male rats. Relative expression of ANG II type 1 receptor mRNA was decreased in the subfornical organ of adult and old male rats as well as adult female rats in response to WD. In conclusion, the study elucidated the effect of sex and age on responses induced by WD, altering the degree of dehydration induced by 48 h of WD.


Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Bryan K Becker ◽  
Amanda C Feagans ◽  
Chunhua Jin ◽  
David M Pollock

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.


2002 ◽  
Vol 283 (2) ◽  
pp. H562-H567 ◽  
Author(s):  
Denise M. Galipeau ◽  
Linfu Yao ◽  
John H. McNeill

Hyperinsulinemia and insulin resistance have been linked to hypertension; however, the influence of sex on this relationship has not been well studied. The purpose of this experiment was to compare the effects of chronic insulin treatment on insulin sensitivity and blood pressure in male and female rats. Male and female Wistar rats were treated with insulin (2 U/day) via subcutaneous sustained release implants for 5 wk. Systolic blood pressure was measured via the tail-cuff method before and after treatment, and insulin sensitivity was assessed with an oral glucose tolerance test. The insulin sensitivity of female rats was 4.5-fold greater than male rats. Chronic insulin treatment impaired insulin sensitivity in both sexes; however, this occurred to a greater degree in male rats. Blood pressure increased in male rats treated with insulin only. The results demonstrate that hyperinsulinemia and insulin resistance are associated with hypertension in male rats only. Therefore, the link between these conditions appears to depend on sex.


2013 ◽  
Vol 2 (3) ◽  
pp. 146
Author(s):  
Mutia Lailani ◽  
Zulkarnain Edward ◽  
Rahmatina B Herman

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


Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Wenjie Wu ◽  
Sydney Murphy

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


1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Song ◽  
Fang Yuan ◽  
Xiaohong Li ◽  
Xipeng Ma ◽  
Xinmin Yin ◽  
...  

Abstract Background Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). Results Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.


2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.


2021 ◽  
pp. 102796
Author(s):  
Bryan K. Becker ◽  
Jermaine G. Johnston ◽  
Carolyn Young ◽  
Alfredo A. Torres Rodriguez ◽  
Chunhua Jin ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Maryam Malek ◽  
Mehdi Nematbakhsh

Background. Angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor (ACE2/Ang-1-7/MasR) appears to counteract most of the deleterious actions of angiotensin-converting enzyme/angiotensin II/angiotensin II receptor 1 (ACE/Ang II/AT1R) in renal ischemia/reperfusion (I/R) injury but ACE2 activity and its levels are sexually dimorphic in the kidney. This study was designed to evaluate the effects of activation endogenous ACE2 using the diminazene aceturate (DIZE) in renal I/R injury in male and female rats.Methods. 36 Wistar rats were divided into two groups of male and female and each group distinct to three subgroups (n=6). I/R group was subjected to 45 min of bilateral ischemia and 24 h of reperfusion, while treatment group received DIZE (15 mg/kg/day) for three days before the induction of I/R. The other group was assigned as the sham-operated group.Results. DIZE treatment in male rats caused a significant decrease in blood urea nitrogen (BUN), creatinine, liver functional indices, serum malondialdehyde (MDA), and increase kidney nitrite levels (P<0.05), and in female rats a significant increase in creatinine and decrease serum nitrite levels compared to the I/R group (P<0.05).Conclusions. DIZE may protect the male kidney from renal I/RI through antioxidant activity and elevation of circulating nitrite level.


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