scholarly journals Early life stress induces renal dysfunction in adult male rats but not female rats

2013 ◽  
Vol 304 (2) ◽  
pp. R121-R129 ◽  
Author(s):  
Analia S. Loria ◽  
Tatsuo Yamamoto ◽  
David M. Pollock ◽  
Jennifer S. Pollock
Keyword(s):  
Blood Pressure ◽  
Adult Male ◽  
Early Life ◽  
Female Rats ◽  
Male Rats ◽  
Plasma Testosterone ◽  
Ang Ii ◽  
Control Female ◽  
Induced Hypertension ◽  
And Control

Maternal separation (MatSep) is a model of behavioral stress during early life. We reported that MatSep exacerbates ANG II-induced hypertension in adult male rats. The aims of this study were to determine whether exposure to MatSep in female rats sensitizes blood pressure to ANG II infusion similar to male MatSep rats and to elucidate renal mechanisms involved in the response in MatSep rats. Wistar Kyoto (WKY) pups were exposed to MatSep 3 h/day from days 2 to 14, while control rats remained with their mothers. ANG II-induced mean arterial pressure (MAP; telemetry) was enhanced in female MatSep rats compared with control female rats but delayed compared with male MatSep rats. Creatinine clearance (Ccr) was reduced in male MatSep rats compared with control rats at baseline and after ANG II infusion. ANG II infusion significantly increased T cells in the renal cortex and greater histological damage in the interstitial arteries of male MatSep rats compared with control male rats. Plasma testosterone was greater and estradiol was lower in male MatSep rats compared with control rats with ANG II infusion. ANG II infusion failed to increase blood pressure in orchidectomized male MatSep and control rats. Female MatSep and control rats had similar Ccr, histological renal analysis, and sex hormones at baseline and after ANG II infusion. These data indicate that during ANG II-induced hypertension, MatSep sensitizes the renal phenotype in male but not female rats.

scholarly journals Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth-restricted offspring

2010 ◽  
Vol 298 (5) ◽  
pp. R1421-R1427 ◽  
Author(s):  
Norma B. Ojeda ◽  
Thomas P. Royals ◽  
Joshua T. Black ◽  
John Henry Dasinger ◽  
Jeremy M. Johnson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adult Male ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Underlying Mechanism ◽  
Male Rats ◽  
Ang Ii ◽  
Enhanced Sensitivity ◽  
And Control

Placental insufficiency results in intrauterine growth restriction (IUGR) and hypertension in adult male growth-restricted rats. Although renal ANG II and plasma renin activity do not differ between growth-restricted and control rats, blockade of the renin-angiotensin system (RAS) abolishes hypertension in growth-restricted rats, suggesting that the RAS contributes to IUGR-induced hypertension. Moreover, castration abolishes hypertension in growth-restricted rats, indicating an important role for testosterone. Therefore, we hypothesized that enhanced responsiveness to ANG II contributes to hypertension in this model of IUGR and that androgens may play a pivotal role in this enhanced response. Physiological parameters were determined at 16 wk of age in male rats pretreated with enalapril (40 mg·kg−1·day−1) for 1 wk. Baseline blood pressures were similar between growth-restricted (112 ± 3 mmHg) and control (110 ± 2 mmHg) rats; however, an enhanced pressor response to acute ANG II (100 ng·kg−1·min−1 for 30 min) was observed in growth-restricted (160 ± 2 mmHg) vs. control (136 ± 2 mmHg; P < 0.05) rats. Castration abolished the enhanced pressor response to acute ANG II in growth-restricted (130 ± 2 mmHg) rats with no significant effect on blood pressure in controls (130 ± 2 mmHg). Blood pressure was increased to a similar extent above baseline in response to acute phenylephrine (100 μg/min) in control (184 ± 5 mmHg) and growth-restricted (184 ± 8 mmHg) rats, suggesting the enhanced pressor response in growth-restricted rats is ANG II specific. Thus, these results suggest that growth-restricted rats exhibit an enhanced responsiveness to ANG II that is testosterone dependent and indicate that the RAS may serve as an underlying mechanism in mediating hypertension programmed in response to IUGR.

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
Keyword(s):  
Blood Pressure ◽  
High Salt ◽  
Female Rats ◽  
Male Rats ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Male And Female ◽  
Male And Female Rats ◽  
Endothelin B

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.

Sex as a determining factor in the effect of exercise on in vivo autoimmune response adjuvant arthritis

1994 ◽  
Vol 76 (3) ◽  
pp. 1172-1175 ◽  
Author(s):  
A. Ferry ◽  
C. Le Page ◽  
M. Rieu
Keyword(s):  
Adjuvant Arthritis ◽  
Clinical Signs ◽  
Female Rats ◽  
Male Rats ◽  
Autoimmune Response ◽  
Human Rheumatoid Arthritis ◽  
Control Female ◽  
And Control ◽  
Arthritic Joints

The present study was conducted to examine the effect of physical exercise on the development of adjuvant arthritis (AA), an animal model of the human rheumatoid arthritis, which is a T-cell-dependent autoimmune response. AA was inducted on day 0 in 8-wk-old Lewis rats of both sexes. Between postinjection days 1 and 12, two groups of rats (male and female) were trained on a treadmill every day (45–120 min/day and 15–30 m/min) before the onset of arthritic disease. Trained female (n = 27) and male (n = 22) rats and control female (n = 29) and male (n = 17) rats were observed every 2 days for the following clinical signs of AA: number of arthritic joints (swelling and redness), paw thickness, and weight gain during the disease. The results show that the incidence of arthritis (% of arthritic rats) was significantly higher in trained female rats (74%; P < 0.03) and significantly lower in trained male rats (27%; P < 0.05) compared with control rats of both sexes (female, 45%; male, 59%). There was no difference in the severity and development of the disease between trained rats and control rats of both sexes (P > 0.05). The present study indicates that the effect of exercise on the incidence of AA, an in vivo autoimmune response, depends on the sex of the animal.

Female rats are protected against fructose-induced changes in metabolism and blood pressure

2002 ◽  
Vol 283 (6) ◽  
pp. H2478-H2484 ◽  
Author(s):  
Denise Galipeau ◽  
Subodh Verma ◽  
John H. McNeill
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Female Rats ◽  
Male Rats ◽  
Oral Glucose ◽  
Metabolic Parameter ◽  
Female Sex Hormones ◽  
Glucose Tolerance Tests ◽  
Induced Changes ◽  
And Control

The objective of this study was to determine whether the effects of a fructose diet, which causes hyperinsulinemia, insulin resistance, and hypertension in male rats, are dependent on sex. Blood pressure was measured via the tail-cuff method, and oral glucose tolerance tests were performed to assess insulin sensitivity. Blood pressure in female rats did not differ between fructose-fed and control rats at any time point (126 ± 5 and 125 ± 3 mmHg at week 9 for fructose-fed and control rats, respectively) nor was there a difference in any metabolic parameter measured. Furthermore, the vascular insulin resistance that is present in male fructose-fed rats was not observed. After ovariectomy, fructose caused a significant change in systolic blood pressure from baseline compared with fructose-fed ovary-intact rats (change of 21 ± 5 vs. −2 ± 4 mmHg). The results demonstrate that females do not develop hypertension or hyperinsulinemia upon fructose feeding except after ovariectomy, suggesting that female sex hormones may confer protection against the effects of a fructose diet.

CYANOKETONE-INDUCED INHIBITION OF ADRENAL 3β-HYDROXY-Δ5-STEROID OXIDOREDUCTASE ACTIVITY IN FEMALE AND MALE RATS IN VITRO

1976 ◽  
Vol 83 (3) ◽  
pp. 576-582 ◽  
Author(s):  
Sven A. Gustafsson
Keyword(s):  
Sex Differences ◽  
Single Injection ◽  
Female Rats ◽  
Male Rats ◽  
Oxidoreductase Activity ◽  
Control Female ◽  
Lower Affinity ◽  
And Control

ABSTRACT The inhibition of adrenal 3β-hydroxy-Δ5-steroid oxidoreductase activity was studied in vitro 24 h after a single injection of 2α-cyano-4,4,17α-trimethyl-5-androsten-17β-ol-3-one (cyanoketone) to adult castrated female and male rats. The inhibition of conversion of dehydroepiandrosterone1) to androstenedione was about 80 % as compared to adult castrated control rats treated with vehicle only. The conversion of pregnenolone to progesterone and 5α-pregnane-3,20-dione was also inhibited by about 80 % in both sexes. The activity of 3β-hydroxy-Δ5-steroid oxidoreductase was greater both in cyanoketone-treated and control female rats as compared to the corresponding male rats. It is concluded that the previously observed sex differences in response to cyanoketone in vivo are not due to a lower affinity of male adrenal 3β-hydroxy-Δ5-steroid oxidoreductase to cyanoketone.

Abstract MP03: ROCK2 Specific Inhibition Attenuates Angiotensin II-induced Hypertension In Mice

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Daniel J Fehrenbach ◽  
Meena S Madhur
Keyword(s):  
Blood Pressure ◽  
T Cell ◽  
Angiotensin Ii ◽  
Repeated Measures ◽  
Flow Cytometric Analysis ◽  
Coiled Coil ◽  
Ang Ii ◽  
Induced Hypertension

Hypertension, or an elevated blood pressure, is the primary modifiable risk factor for cardiovascular disease, the number one cause of mortality worldwide. We previously demonstrated that Th17 activation and interleukin 17A (IL-17A)/IL-21 production is integral for the full development of a hypertensive phenotype as well as the renal and vascular damage associated with hypertension. Rho-associated coiled-coil containing protein Kinase 2 (ROCK2) serves as a molecular switch upregulating Th17 and inhibiting regulatory T cell (Treg) differentiation. We hypothesize that hypertension is characterized by excessive T cell ROCK2 activation leading to increased Th17/Treg ratios and ultimately end-organ damage. We first showed in vitro that KD025, an experimental orally bioavailable ROCK2 inhibitor inhibits Th17 cell proliferation and IL-17A/IL-21 production. To determine if hypertensive stimuli such as endothelial stretch increases T cell ROCK2 expression, we cultured human aortic endothelial cells exposed to 5% (normotensive) or 10% (hypertensive) stretch with circulating human T cells and HLA-DR+ antigen presenting cells. Hypertensive stretch increased T cell ROCK2 expression 2-fold. We then tested the effect of ROCK2 inhibition with KD025 (50mg/kg i.p. daily) in vivo on angiotensin II (Ang II)-induced hypertension. Treatment with KD025 significantly attenuated the hypertensive response within 1 week of Ang II treatment (systolic blood pressure: 139± 8 vs 108±7mmHg) and this persisted for the duration of the 4 week study reaching blood pressures 20 mmHg lower (135±13mmHg) than vehicle treated mice (158±4mmHg p<0.05 effect of treatment 2-way Repeated Measures ANOVA). Flow cytometric analysis of tissue infiltrating leukocytes revealed that KD025 treatment increased Treg/Th17 ratios in the kidney (0.61±0.03 vs 0.79±0.08, p<0.05 student’s t-test). Thus, T cell ROCK2 may be a novel therapeutic target for the treatment of hypertension.

Splenocyte transfer from hypertensive donors eliminates premenopausal female protection from Ang II-induced hypertension

2022 ◽  
Author(s):  
Megan A Sylvester ◽  
Dennis P Pollow ◽  
Caitlin Moffett ◽  
Wendy Nunez ◽  
Jennifer L Uhrlaub ◽  
...  
Keyword(s):  
Blood Pressure ◽  
T Cells ◽  
Adoptive Transfer ◽  
T Regulatory Cells ◽  
Estrogen Signaling ◽  
Ang Ii ◽  
Regulatory Cells ◽  
Adaptive Immune Cells ◽  
Induced Hypertension ◽  
Rag 1

Premenopausal females are protected from Angiotensin II (Ang II)-induced hypertension following the adoptive transfer of T cells from normotensive donors. For the present study, we hypothesized that the transfer of hypertensive T cells (HT) or splenocytes (HS) from hypertensive donors would eliminate premenopausal protection from hypertension. Premenopausal Rag-1-/- females received either normotensive (NT) or hypertensive cells, three weeks prior to Ang II infusion (14 days, 490 ng/kg/min). Contrary to our hypothesis, no increase in Ang II-induced blood pressure was observed in the NT/Ang or HT/Ang groups. Flow cytometry demonstrated that renal FoxP3+ T regulatory cells were significantly decreased and IHC showed an increase in renal F4/80+ macrophages in HT/Ang, suggesting a shift in the renal inflammatory environment despite no change in blood pressure. Renal mRNA expression of MCP-1, Endothelin-1, GPER-1 were significantly decreased in HT/Ang. The adoptive transfer of hypertensive splenocytes prior to Ang II infusion (HS/Ang) eliminated premenopausal protection from hypertension and significantly decreased splenic FoxP3+ T regulatory cells compared to females receiving normotensive splenocytes (NS/Ang). Expression of MIP-1a/CCL3, a potent macrophage chemokine was elevated in HS/Ang, however no increase in renal macrophage infiltration occurred. Together, these data show that in premenopausal females T cells from hypertensive donors are not sufficient to induce a robust Ang II mediated hypertension, in contrast, transfer of hypertensive splenocytes (consisting of T/B lymphocytes, dendritic cells, macrophages) is sufficient. Further work is needed to understand how innate and adaptive immune cells and estrogen signaling coordinate to cause differential hypertensive outcomes in premenopausal females.

scholarly journals Subchronic toxicity of aqueous extract of Alstonia boonei de wild. (apocynaceae) stem bark in normal rats

2015 ◽  
Vol 3 (1) ◽  
pp. 5 ◽  
Author(s):  
Barnabé Lucien Nkono Ya Nkono ◽  
Selestin Dongmo Sokeng ◽  
Paul Désiré Dzeufiet Djomeni ◽  
Frida Longo ◽  
Pierre Kamtchouing
Keyword(s):  
Aqueous Extract ◽  
Biochemical Study ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
Control Male ◽  
Control Female ◽  
Hematological Analysis ◽  
Wbc Count ◽  
Dose Dependent

<p><strong>Methodology:</strong> Wistar rats were randomly assigned into eight groups of five animals each: four male groups and four female groups. Each sex group had a control group receiving distilled water and three test groups receiving 200, 500 and 1000mg/kg respectively. Animal’s body weights were recorded on the first day and once a week for the four experiment weeks. The hematological analysis included total WBC count, total RBC count, Hb, %HCT, MCV, MCH and MCHC. Biochemical/serum profile studies include TG, TC, ALT, AST, urea and TP. Tissue specimens of the liver, kidney and lung were subjected to histological examination using standard hematoxylin-eosin staining.</p><p><strong>Results:</strong> In male rats, aqueous extract showed significant decreases in relative weight of liver with extreme significance P&lt;0.001 at a dose of 200mg/kg (vs. control group), P&lt;0.001 of lung at all the doses, P&lt;0.05 (200 and 500mg/kg) and P&lt;0.01 (1000mg/kg) in heart weight. In relative kidney weight, only the dose of 1000mg/kg showed a significant increase vs. normal control male rats. Unlike male rats, only relative kidney weight in female rats was significantly different from the control group in a dose-dependent manner. The aqueous extract treated male groups showed significant increases P&lt;0.001 (1000mg/kg) of total WBC count and MCHC, significant decreases of %HTC (dose response manner), P&lt;0.05 total RBC count (at doses of 500 and 1000mg/kg) and Hb P&lt;0.01 (500mg/kg) vs. normal male rats. In female rats, the haematological study showed significant increase P&lt;0.01 of total WBC count (at the doses of 500 and 1000mg/kg), significant decreases P&lt;0.05 and P&lt;0.01 of total RBC respectively at the doses of 200 and 1000mg/kg, significant decrease of Hb with extreme significance P&lt;0.001 at the dose 1000mg/kg, %HTC also decrease dose response manner vs. control female rats. Biochemical study showed in male rats significant decreases in level of TG P&lt;0.001 (at the doses of 200 and 500mg/kg) and urea, although it showed any dose-dependent effect vs. control male rats. AST also decreases (P&lt;0.05) in male rats at the dose of 200mg/kg but significantly increase P&lt;0.001 at the dose of 500mg/kg. In the female rats, biochemical study revealed significant increases in level of TG P&lt;0.001 and urea P&lt;0.01 at the dose of 200mg/kg and significant decreases in level of TG P&lt;0.01, AST P&lt;0.05 and urea P&lt;0.05 at the dose of 500mg/kg (vs. control female rats). Microscopically, there were mild hepatic and renal tissue injuries supporting the hematological analysis.</p><p><strong>Conclusion:</strong> The results indicated that aqueous extract of <em>Alstonia boonei</em> De Wild is toxic in high doses.</p>

Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats

2003 ◽  
Vol 285 (2) ◽  
pp. F295-F302 ◽  
Author(s):  
Mong-Heng Wang ◽  
Jishi Wang ◽  
Hsin-Hsin Chang ◽  
Barbara A. Zand ◽  
Miao Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Rat Kidney ◽  
Late Pregnancy ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Male Rats ◽  
Pregnant Rats ◽  
Renal Vasoconstriction ◽  
Dependent Inhibition

20-Hydroxyeicosatetraenoic acid (20-HETE), which promotes renal vasoconstriction, is formed in the rat kidney primarily by cytochrome P-450 (CYP) 4A isoforms (4A1, 4A2, 4A3, 4A8). Nitric oxide (NO) has been shown to bind to the heme moiety of the CYP4A2 protein and to inhibit 20-HETE synthesis in renal arterioles of male rats. However, it is not known whether NO interacts with and affects the activity of CYP4A1 and CYP4A3, the major renal CYP4A isoforms in female rats. Incubation of recombinant CYP4A1 and 4A3 proteins with sodium nitroprusside (SNP) shifted the absorbance at 440 nm, indicating the formation of a ferric-nitrosyl-CYP4A complex. The absorbance for CYP4A3 was about twofold higher than that of CYP4A1. Incubation of SNP or peroxynitrite (PN; 0.01–1 mM) with CYP4A recombinant membranes caused a concentration-dependent inhibition of 20-HETE synthesis, with both chemicals having a greater inhibitory effect on CYP4A3-catalyzed activity. Moreover, incubation of CYP4A1 and 4A3 proteins with PN (1 mM) resulted in nitration of tyrosine residues in both proteins. In addition, PN and SNP inhibited 20-HETE synthesis in renal microvessels from female rats by 65 and 59%, respectively. We previously showed that microvessel CYP4A1/CYP4A3 expression and 20-HETE synthesis are decreased in late pregnancy. Therefore, we investigated whether such a decrease is dependent on NO, the synthesis of which has been shown to increase in late pregnancy. Administration of NG-nitro-l-arginine methyl ester (l-NAME) to pregnant rats for 6 days ( days 15- 20 of pregnancy) caused a significant increase in systolic blood pressure, which was prevented by concurrent treatment with the CYP4A inhibitor 1-aminobenzotriazole (ABT). Urinary NO2/NO3 excretion decreased by 40 and 52% in l-NAME- and l-NAME + ABT-treated groups, respectively. Interestingly, renal microvessel 20-HETE synthesis showed a marked increase following l-NAME treatment, and this increase was diminished with coadministration of ABT. These results demonstrate that NO interacts with CYP4A proteins in a distinct manner and it interferes with renal microvessel 20-HETE synthesis, which may play an important role in the regulation of blood pressure and renal function during pregnancy.

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