scholarly journals Genotype-Related Effect of Crowding Stress on Blood Pressure and Vascular Function in Young Female Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Peter Slezak ◽  
Angelika Puzserova ◽  
Peter Balis ◽  
Natalia Sestakova ◽  
Miroslava Majzunova ◽  
...  

This study investigated the influence of chronic crowding stress on nitric oxide (NO) production, vascular function and oxidative status in young Wistar-Kyoto (WKY), borderline hypertensive (BHR) and spontaneously hypertensive (SHR) female rats. Five-week old rats were exposed to crowding for two weeks. Crowding elevated plasma corticosterone(P<0.05)and accelerated BP (P<0.01versus basal) only in BHR. NO production and superoxide concentration were significantly higher in the aortas of control BHR and SHR versus WKY. Total acetylcholine (ACh)-induced relaxation in the femoral artery was reduced in control SHR versus WKY and BHR, and stress did not affect it significantly in any genotype. The attenuation of ACh-induced relaxation in SHR versus WKY was associated with reduction of its NO-independent component. Crowding elevated NO production in all strains investigated but superoxide concentration was increased only in WKY, which resulted in reduced NO-dependent relaxation in WKY. In crowded BHR and SHR, superoxide concentration was either unchanged or reduced, respectively, but NO-dependent relaxation was unchanged in both BHR and SHR versus their respective control group. This study points to genotype-related differences in stress vulnerability in young female rats. The most pronounced negative influence of stress was observed in BHR despite preserved endothelial function.

2018 ◽  
Vol 132 (14) ◽  
pp. 1513-1527 ◽  
Author(s):  
Alynne Carvalho-Galvão ◽  
Blessing Ogunlade ◽  
Jiaxi Xu ◽  
Cristiane R.A. Silva-Alves ◽  
Leônidas G. Mendes-Júnior ◽  
...  

TRV027 is a biased agonist for the Angiotensin (Ang)-II type 1 receptor (AT1R), able to recruit β-arrestin 2 independently of G-proteins activation. β-arrestin activation in the central nervous system (CNS) was suggested to oppose the effects of Ang-II. The present study evaluates the effect of central infusion of TRV027 on arterial pressure (AP), autonomic function, baroreflex sensitivity (BRS), and peripheral vascular reactivity. Spontaneously hypertensive (SH) and Wistar Kyoto (WKY) rats were treated with TRV027 for 14 days (20 ng/h) delivered to the lateral ventricle via osmotic minipumps. Mechanistic studies were performed in HEK293T cells co-transfected with AT1R and Ang converting enzyme type 2 (ACE2) treated with TRV027 (100 nM) or Ang-II (100 nM). TRV027 infusion in SH rats (SHR) reduced AP (~20 mmHg, P<0.05), sympathetic vasomotor activity (ΔMAP = −47.2 ± 2.8 compared with −64 ± 5.1 mmHg, P<0.05) and low-frequency (LF) oscillations of AP (1.7 ± 0.2 compared with 5.8 ± 0.4 mmHg, P<0.05) compared with the SHR control group. TRV027 also increased vagal tone, improved BRS, reduced the reactivity of mesenteric arteries to Ang-II and increased vascular sensitivity to phenylephrine (Phe), acetylcholine, (ACh), and sodium nitroprusside (SNP). In vitro, TRV027 prevented the Ang-II-induced up-regulation of ADAM17 and in contrast with Ang-II, had no effects on ACE2 activity and expression levels. Furthermore, TRV027 induced lesser interactions between AT1R and ACE2 compared with Ang-II. Together, these data suggest that due to its biased activity for the β-arrestin pathway, TRV027 has beneficial effects within the CNS on hypertension, autonomic and vascular function, possibly through preserving ACE2 compensatory activity in neurones.


2019 ◽  
Vol 25 (1) ◽  
Author(s):  
ASHOK KUMAR ◽  
ALPANA PARMAR ◽  
ANAND KUMAR BAJPEYEE

Young female Black rat (Rattus rattus), were administered monthly long acting steroid contraceptive to induce hypertriglyceridemia. It was observed that by 3 weeks of the second injection of estrogen containing mixed type of contraceptive, female rats developed consistent and frank hyperglyceridemia . TG in the treated rats was 195.8 ± 7.44 mg /100 ml as compared to 91.5 ± 6.27 mg/100ml in plasma of the control group.


Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 676
Author(s):  
Kunanya Masodsai ◽  
Yi-Yuan Lin ◽  
Sih-Yin Lin ◽  
Chia-Ting Su ◽  
Shin-Da Lee ◽  
...  

This study aimed to investigate the aging-related endothelial dysfunction mediated by insulin and insulin-like growth factor-1 (IGF-1) and antioxidant deficiency in hypertension. Male spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar–Kyoto rats (WKYs) were randomly divided into 24-week-old (younger) and 48-week-old (older) groups, respectively. The endothelial function was evaluated by the insulin- and IGF-1-mediated vasorelaxation of aortic rings via the organ bath system. Serum levels of nitric oxide (NO), malondialdehyde (MDA), catalase, and total antioxidant capacity (TAC) were examined. The insulin- and IGF-1-mediated vasorelaxation was significantly impaired in both 24- and 48-week-old SHRs compared with age-matched WKYs and was significantly worse in the 48-week-old SHR than the 24-week-old SHR. After pretreatments of phosphoinositide 3-kinase (PI3K) or NO synthase (NOS) inhibitors, the insulin- and IGF-1-mediated vasorelaxation became similar among four groups. The serum level of MDA was significantly increased, while the NO, catalase, and TAC were significantly reduced in the 48-week-old SHR compared with the 24-week-old SHR. This study demonstrated that the process of aging additively affected insulin- and IGF-1-mediated endothelial dysfunction in SHRs, which could be partly attributed to the reduced NO production and antioxidant deficiency.


2014 ◽  
Vol 39 (11) ◽  
pp. 1280-1285 ◽  
Author(s):  
Aleksandra Mazur ◽  
Peter Buzzacott ◽  
Kate Lambrechts ◽  
Qiong Wang ◽  
Marc Belhomme ◽  
...  

Vascular bubble formation results from supersaturation during inadequate decompression contributes to endothelial injuries, which form the basis for the development of decompression sickness (DCS). Risk factors for DCS include increased age, weight–fat mass, decreased maximal oxygen uptake, chronic diseases, dehydration, and nitric oxide (NO) bioavailability. Production of NO is often affected by diving and its expression–activity varies between the genders. Little is known about the influence of sex on the risk of DCS. To study this relationship we used an animal model of Nω-nitro-l-arginine methyl ester (l-NAME) to induce decreased NO production. Male and female rats with diverse ages and weights were divided into 2 groups: treated with l-NAME (in tap water; 0.05 mg·mL–1 for 7 days) and a control group. To control the distribution of nitrogen among tissues, 2 different compression–decompression protocols were used. Results showed that l-NAME was significantly associated with increased DCS in female rats (p = 0.039) only. Weight was significant for both sexes (p = 0.01). The protocol with the highest estimated tissue pressures in the slower compartments was 2.6 times more likely to produce DCS than the protocol with the highest estimated tissue pressures in faster compartments. The outcome of this study had significantly different susceptibility to DCS after l-NAME treatment between the sexes, while l-NAME per se had no effect on the likelihood of DCS. The analysis also showed that for the appearance of DCS, the most significant factors were type of protocol and weight.


2011 ◽  
Vol 122 (5) ◽  
pp. 215-226 ◽  
Author(s):  
Fernanda R. C. Giachini ◽  
Victor V. Lima ◽  
Fernando P. Filgueira ◽  
Anne M. Dorrance ◽  
Maria Helena C. Carvalho ◽  
...  

Sex differences in Ca2+-dependent signalling and homoeostasis in the vasculature of hypertensive rats are well characterized. However, sex-related differences in SOCE (store-operated Ca2+ entry) have been minimally investigated. We hypothesized that vascular protection in females, compared with males, reflects decreased Ca2+ mobilization due to diminished activation of Orai1/STIM1 (stromal interaction molecule 1). In addition, we investigated whether ovariectomy in females affects the activation of the Orai1/STIM1 pathway. Endothelium-denuded aortic rings from male and female SHRSP (stroke-prone spontaneously hypertensive rats) and WKY (Wistar–Kyoto) rats and from OVX (ovariectomized) or sham female SHRSP and WKY rats were used to functionally evaluate Ca2+ influx-induced contractions. Compared with females, aorta from male SHRSP displayed: (i) increased contraction during the Ca2+-loading period; (ii) similar transient contraction during Ca2+ release from the intracellular stores; (iii) increased activation of STIM1 and Orai1, as shown by the blockade of STIM1 and Orai1 with neutralizing antibodies, which reversed the sex differences in contraction during the Ca2+-loading period; and (iv) increased expression of STIM1 and Orai1. Additionally, we found that aortas from OVX-SHRSP showed increased contraction during the Ca2+-loading period and increased Orai1 expression, but no changes in the SR (sarcoplasmic reticulum)-buffering capacity or STIM1 expression. These findings suggest that augmented activation of STIM1/Orai1 in aortas from male SHRSP represents a mechanism that contributes to sex-related impaired control of intracellular Ca2+ levels. Furthermore, female sex hormones may negatively modulate the STIM/Orai1 pathway, contributing to vascular protection observed in female rats.


Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0002722021
Author(s):  
Giannie Barsha ◽  
Sarah L Walton ◽  
Edmund Kwok ◽  
Katrina M Mirabito Colafella ◽  
Anita P Pinar ◽  
...  

Background: The anti-fibrotic effects of recombinant human relaxin (RLX) in the kidney are dependent on an interaction between its cognate receptor (RXFP1) and the angiotensin type 2 receptor (AT2R) in male models of disease. Whether RLX has therapeutic effects, which are also mediated via the AT2R, in hypertensive adult and aged/reproductively senescent females is unknown. Thus, we determined whether treatment with RLX provides cardiorenal protection, via an AT2R-dependent mechanism, in adult and aged female stroke prone-spontaneously hypertensive rats (SHRSP). Methods: In 6- (6MO) and 15-month-old (15MO; reproductively senescent) female SHRSP, systolic blood pressure (SBP), glomerular filtration rate (GFR) and proteinuria were measured before and after 4 weeks treatment with vehicle (Veh), RLX (0.5 mg/kg/day s.c.) or RLX+PD123319 (AT2R antagonist; 3 mg/kg/day s.c.). Aortic endothelium-dependent relaxation and fibrosis of the kidney, heart and aorta were assessed. Results: In 6MO SHRSP, RLX significantly enhanced GFR by ~25% (P=0.001) and reduced cardiac fibrosis (P=0.01) as compared to vehicle-treated counterparts. These effects were abolished or blunted by PD123319 co-administration. In 15MO females, RLX reduced interstitial renal (P=0.02) and aortic (P=0.003) fibrosis, and lowered SBP (13±3 mmHg; P=0.04) relative to controls. These effects were also blocked by PD123319 co-treatment (all p<0.05 versus RLX treatment alone). RLX also markedly improved vascular function by ~40% (P<0.0001) in 15MO SHRSP, but this was not modulated by PD123319 co-treatment. Conclusion: The anti-fibrotic and organ-protective effects of RLX, when administered to a severe model of hypertension, conferred cardiorenal protection in adult and reproductively senescent female rats, to a great extent via an AT2R-mediated mechanism.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Lei Zhang ◽  
Jie Yu ◽  
Yingying Liu ◽  
Weixing Guo ◽  
Yunlun Li

Objectives. Yishenjiangyafang is a traditional Chinese medicine used to clinically treat hypertension. This study aimed to explore the effect of yishenjiangyafang on plasma metabolomics in senile spontaneously hypertensive rats (SHRs). Methods. Twelve 50-week-old SHR (6 males and 6 females) were randomly divided into two groups: a treatment group, in which rats were intragastrically administered with yishenjiangyafang (10.08 g kg−1·d−1), and a model group, in which all SHRs were administered the same volume of saline. Six age- and gender-matched Wistar–Kyoto (WKY) rats were used as the control group. Treatment was given for 6 days per week and lasted for 8 weeks. Systolic and diastolic blood pressures of the rats were measured with the noninvasive tail artery pressure measurement system. An ultraperformance liquid chromatography quadruple electrostatic field orbit (UPLC-Q-Exactive) was used to determine metabolite changes in the plasma of SHR rats before and after yishenjiangyafang treatment in the treatment group as well as in the model and control groups. Results. After yishenjiangyafang treatment, SHRs had significant lower blood pressure. Using UPLC-Q-Exactive, we identified 26 metabolic targets of yishenjiangyafang in aged SHRs and revealed that yishenjiangyafang targeted four major metabolic pathways, linoleic acid metabolism, glycerophospholipid metabolism, arginine and proline metabolism, and steroid hormone biosynthesis. Conclusion. Yishenjiangyafang decreases the blood pressure of SHRs at least in part through targeting of four major metabolic pathways. Our study illustrates mechanisms underlying the clinical application of yishenjiangyafang in the treatment of hypertensive patients.


1998 ◽  
Vol 274 (2) ◽  
pp. R510-R516 ◽  
Author(s):  
Margaret P. Chandler ◽  
Stephen E. Dicarlo

Arterial pressure (AP), heart rate (HR), cardiac sympathetic tonus (ST), and parasympathetic tonus (PT) were determined in spontaneously hypertensive rats (SHR, 8 male and 8 female) and Wistar-Kyoto normotensive rats (WKY, 8 male and 12 female) before and after acute exercise. Before exercise, hypertensive rats (regardless of gender) had an increased ST (+15 beats/min), increased resting HR (+12 beats/min), and decreased PT (−11 beats/min). Similarly, female rats (regardless of strain) also had an increased ST (+15 beats/min), increased resting HR (+39 beats/min), and decreased PT (−14 beats/min). Hypertensive rats had a significant reduction in AP (−17 ± 3 mmHg), ST (−26 beats/min), PT (−7 beats/min), and HR (−14 beats/min) after exercise. In contrast, AP was not reduced in normotensive rats and ST (+18 beats/min) and HR (+42 beats/min) were increased in female normotensive rats after exercise. However, male normotensive rats had a postexercise reduction in ST (−14 beats/min) and HR (−19 beats/min). In summary, AP, ST, and resting HR were higher whereas PT was lower in hypertensive vs. normotensive rats. Furthermore, females had a higher resting HR, intrinsic HR, and ST and lower PT than male rats. These data demonstrate that gender and the resting level of AP influence cardiac autonomic regulation.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
John P Valenzuela ◽  
Weiguo Li ◽  
Yasir Abdul ◽  
Rebecca Ward ◽  
Sally El-Shafey ◽  
...  

Women are protected from stroke until they reach menopause in part due to neuroprotection conferred by sex hormones. We and others have shown that that diabetes increases neurovascular injury and worsens stroke outcomes in males. Given the clinical evidence that diabetes increases stroke risk especially in younger individuals and females, we hypothesized that diabetes worsens stroke outcome even in young females. We further postulated that moderate hyperglycemia worsens hemorrhagic transformation (HT) and outcomes independent of changes in infarct size. High fat diet plus low dose streptozotocin model of diabetes was used. Control and diabetic weight-matched male and female rats (10-12 weeks old, n=5-7) were subjected to embolic stroke with a fibrin-rich humanized clot. Neurological deficits (Bederson score, adhesive removal test -ART and grip strength), infarct size, HT index, and edema ratio were assessed 3 days after surgery (Table). As expected in the control group, females rats had smaller infarct size, less edema, and better functional outcomes as compared to male rats. In the diabetic group, however, HT score was greater and this was more profound in females. Diabetes worsened the functional outcome to a much greater extent in females. While there was partial improvement of neurological deficits by Day 3 in control animals, diabetic animals did not improve but worsened. Additional studies will explore the long-term effects and the underlying mechanisms contributing to worse outcome in young and old diabetic females.


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