Impact of gonadectomy on blood pressure regulation in ageing male and female rats

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.

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Fetal Undernutrition Induces Resistance Artery Remodeling and Stiffness in Male and Female Rats Independent of Hypertension

Biomedicines ◽

10.3390/biomedicines8100424 ◽

2020 ◽

Vol 8 (10) ◽

pp. 424

Author(s):

Perla Y. Gutiérrez-Arzapalo ◽

Pilar Rodríguez-Rodríguez ◽

David Ramiro-Cortijo ◽

Marta Gil-Ortega ◽

Beatriz Somoza ◽

...

Keyword(s):

Blood Pressure ◽

Blood Pressure Level ◽

Female Rats ◽

Resistance Artery ◽

Male And Female ◽

Maternal Undernutrition ◽

Male And Female Rats ◽

Males And Females ◽

Artery Remodeling ◽

Tail Cuff

Fetal undernutrition programs hypertension and cardiovascular diseases, and resistance artery remodeling may be a contributing factor. We aimed to assess if fetal undernutrition induces resistance artery remodeling and the relationship with hypertension. Sprague–Dawley dams were fed ad libitum (Control) or with 50% of control intake between days 11 and 21 of gestation (maternal undernutrition, MUN). In six-month-old male and female offspring we assessed blood pressure (anesthetized and tail-cuff); mesenteric resistance artery (MRA) structure and mechanics (pressure myography), cellular and internal elastic lamina (IEL) organization (confocal microscopy) and plasma MMP-2 and MMP-9 activity (zymography). Systolic blood pressure (SBP, tail-cuff) and plasma MMP activity were assessed in 18-month-old rats. At the age of six months MUN males exhibited significantly higher blood pressure (anesthetized or tail-cuff) and plasma MMP-9 activity, while MUN females did not exhibit significant differences, compared to sex-matched controls. MRA from 6-month-old MUN males and females showed a smaller diameter, reduced adventitial, smooth muscle cell density and IEL fenestra area, and a leftward shift of stress-strain curves. At the age of eighteen months SBP and MMP-9 activity were higher in both MUN males and females, compared to sex-matched controls. These data suggest that fetal undernutrition induces MRA inward eutrophic remodeling and stiffness in both sexes, independent of blood pressure level. Resistance artery structural and mechanical alterations can participate in the development of hypertension in aged females and may contribute to adverse cardiovascular events associated with low birth weight in both sexes.

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Sex-specific computational models for blood pressure regulation in the rat

AJP Renal Physiology ◽

10.1152/ajprenal.00376.2019 ◽

2020 ◽

Vol 318 (4) ◽

pp. F888-F900

Author(s):

Sameed Ahmed ◽

Anita T. Layton

Keyword(s):

Blood Pressure ◽

Computational Models ◽

Sympathetic Nerve Activity ◽

Blood Pressure Regulation ◽

Female Rats ◽

Pressure Regulation ◽

Nerve Activity ◽

Renal Sympathetic Nerve Activity ◽

Sodium Handling ◽

Renal Sympathetic

In the past decades, substantial effort has been devoted to the development of computational models of the cardiovascular system. Some of these models simulate blood pressure regulation in humans and include components of the circulatory, renal, and neurohormonal systems. Although such human models are intended to have clinical value in that they can be used to assess the effects and reveal mechanisms of hypertensive therapeutic treatments, rodent models would be more useful in assisting the interpretation of animal experiments. Also, despite well-known sexual dimorphism in blood pressure regulation, almost all published models are gender neutral. Given these observations, the goal of this project is to develop the first computational models of blood pressure regulation for male and female rats. The resulting sex-specific models represent the interplay among cardiovascular function, renal hemodynamics, and kidney function in the rat; they also include the actions of the renal sympathetic nerve activity and the renin-angiotensin-aldosterone system as well as physiological sex differences. We explore mechanisms responsible for blood pressure and renal autoregulation and notable sexual dimorphism. Model simulations suggest that fluid and sodium handling in the kidney of female rats, which differs significantly from males, may contribute to their observed lower salt sensitivity as compared with males. Additionally, model simulations highlight sodium handling in the kidney and renal sympathetic nerve activity sensitivity as key players in the increased resistance of females to angiotensin II-induced hypertension as compared with males.

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Relationship among hyperinsulinemia, insulin resistance, and hypertension is dependent on sex

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00238.2002 ◽

2002 ◽

Vol 283 (2) ◽

pp. H562-H567 ◽

Cited By ~ 30

Author(s):

Denise M. Galipeau ◽

Linfu Yao ◽

John H. McNeill

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Insulin Sensitivity ◽

Insulin Treatment ◽

Tolerance Test ◽

Female Rats ◽

Male Rats ◽

Oral Glucose ◽

Male And Female ◽

Male And Female Rats

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.

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Comparison of Changes in Blood Pressure and Dipsogenic Responsiveness to Angiotensin II in Male and Female Rats Chronically Exposed to Cold

Physiology & Behavior ◽

10.1016/s0031-9384(96)00325-3 ◽

1996 ◽

Vol 60 (6) ◽

pp. 1543-1549 ◽

Cited By ~ 18

Author(s):

ZHONGJIE SUN ◽

MELVIN J FREGLY ◽

NEIL E ROWLAND ◽

J.ROBERT CADE

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Female Rats ◽

Male And Female ◽

Male And Female Rats

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The effects of increased blood pressure induced by phenylephrine on Morris water maze tasks in male and female rats

Journal of North Khorasan University of Medical Sciences ◽

10.29252/jnkums.4.3.363 ◽

2012 ◽

Vol 4 (3) ◽

pp. 363-371

Author(s):

M Rahimi ◽

F Vafaee ◽

MN Shafei ◽

S Niazmand ◽

A Khajavi-Rad ◽

...

Keyword(s):

Blood Pressure ◽

Morris Water Maze ◽

Water Maze ◽

Female Rats ◽

Male And Female ◽

Male And Female Rats

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Abstract T6: Adipocyte Bardet-Biedl Syndrome 1 Gene Is Critical For Blood Pressure Regulation

Hypertension ◽

10.1161/hyp.78.suppl_1.t6 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Yuying Zhao ◽

Deng-Fu Guo ◽

Kamal Rahmouni

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Adipose Tissue ◽

Gene Deletion ◽

Blood Pressure Regulation ◽

Conditional Knockout ◽

Pressure Regulation ◽

Bardet Biedl Syndrome ◽

Male And Female ◽

Fat Pads

Bardet-Biedl syndrome (BBS) proteins have emerged as critical regulators of various physiological functions including blood pressure. The presence of hypertension in BBS patients is consistent with the finding that BBS knockout mice exhibit increased renal sympathetic nerve activity and arterial pressure. However, the role and contribution of Bbs genes in various tissues such as adipose tissue to blood pressure regulation remains unclear. To address this, we generated a novel conditional knockout mouse that lacks the Bbs1 gene in adipocytes by breeding mice bearing floxed alleles of the Bbs1 gene (Bbs1 flox/flox ) with mice expressing Cre specifically in adipocytes (Adiponectin Cre mice). Cre-mediated recombination was verified by loss of Bbs1 expression in fat pads, but not in other tissues such as the kidneys, liver and skeletal muscle. Next, we assessed whether adipocyte Bbs1 gene deletion affects body weight and glucose homeostasis. Interestingly, no body weight phenotype was observed in both male and female Adipo Cre /Bbs1 flox/flox mice compared to their control littermates (males: 40.5±2.9 g vs 37.4±5.1 g; female: 27.7±4.0 g vs 27.5±3.6 g; 16 weeks old). However, insulin tolerance test uncovered impaired insulin-induced glucose clearance in both male and female Adipo Cre /Bbs1 flox/flox mice. Subsequently, we measured blood pressure and found that Adipo Cre /Bbs1 flox/flox mice have a remarkable increase in systolic blood pressure (130.4±11.2 mmHg) compared to the control littermates (119.1±4.5 mmHg, p <0.05). Finally, measurement of the expression of the renin-angiotensin system components revealed significantly elevated angiotensinogen mRNA (2.43±1.31 AU vs 1±0.72 AU, p <0.01) and angiotensin-converting enzyme mRNA (2.96±2.51 AU vs 1±0.95 AU, p <0.05) in peri-renal adipose tissue, but not in other fat pads such as brown and inguinal adipose tissues. Interestingly, gene expression of angiotensin receptor 1a was not significantly altered by Bbs1 gene deletion. Taken together, our findings demonstrate that Bbs1 gene in adipose tissue play an important role in the control of insulin sensitivity and blood pressure.

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Sex differences and central protective effect of 17β-estradiol in the development of aldosterone/NaCl-induced hypertension

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01255.2008 ◽

2009 ◽

Vol 296 (5) ◽

pp. H1577-H1585 ◽

Cited By ~ 42

Author(s):

Baojian Xue ◽

Daniel Badaue-Passos ◽

Fang Guo ◽

Celso E. Gomez-Sanchez ◽

Meredith Hay ◽

...

Keyword(s):

Blood Pressure ◽

Protective Effect ◽

Protective Role ◽

Female Rats ◽

Sympathetic Outflow ◽

Male And Female ◽

Male And Female Rats ◽

Induced Hypertension ◽

Combined Administration ◽

17Β Estradiol

The present study tested the hypotheses that male and female rats respond differently to subcutaneous infusions of aldosterone (Aldo; 1.8 μg·kg−1·h−1, 1% NaCl to drink; 28 days) and that central estrogen plays a protective role against the development of hypertension. In rats with blood pressure (BP) and heart rate (HR) measured by Data Sciences International telemetry, chronic Aldo/NaCl treatment induced a greater increase in BP in males (Δ25.4 ± 2.4 mmHg) than in females (Δ7.1 ± 2.2 mmHg). Gonadectomy augmented Aldo/NaCl-induced hypertension in females (Δ18.2 ± 2.0 mmHg) but had no effect in males (Δ23.1 ± 2.9 mmHg). Immunohistochemistry for Fra-like activity was higher in the paraventricular nucleus of intact males, castrated males, and ovariectomized (OVX) females compared with intact females after 28 days of Aldo/NaCl treatment. In intact males, central 17β-estradiol (E2) inhibited the Aldo/NaCl increase in BP (Δ10.5 ± 0.8) compared with that in central vehicle plus systemic Aldo/NaCl (Δ26.1 ± 2.5 mmHg) rats. Combined administration of E2 and estrogen receptor antagonist ICI182780 (ICI) blocked the protective effect of E2 (Δ23.2 ± 2.4 mmHg). In intact females central, but not peripheral, infusions of ICI augmented the Aldo/NaCl (Δ20.4 ± 1.8 mmHg) BP increase. Finally, ganglionic blockade after Aldo infusions resulted in a smaller reduction in BP in intact females (−23.9 ± 2.5 mmHg) and in central estrogen-treated males (−30.2 ± 1.0 mmHg) compared with other groups (intact males, −39.3 ± 3.4; castrated males, −41.8 ± 1.9; intact males with central E2 + ICI, −42.3 ± 2.1; OVX females, −40.3 ± 3.3; and intact females with central ICI, −39.1 ± 1.3 mmHg). Chronic Aldo infusion produced increases in NaCl intake and decreases in HR that were both similar in all groups. Taken together, the results indicate that central estrogen plays a protective role in the development of Aldo/NaCl-induced hypertension and that this may result from reduced sympathetic outflow.

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Adrenal Glands in the Development of Renal Hypertension in Rats

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1957.191.3.542 ◽

1957 ◽

Vol 191 (3) ◽

pp. 542-548 ◽

Cited By ~ 13

Author(s):

Melvin J. Fregly

Keyword(s):

Blood Pressure ◽

Time Course ◽

Adrenal Glands ◽

Renal Hypertension ◽

Female Rats ◽

Elevated Blood ◽

Male And Female ◽

Male And Female Rats ◽

Experimental Renal Hypertension ◽

Adrenalectomized Rats

The adrenal glands of the rat do not appear to be necessary for the development of experimental renal hypertension by kidney encapsulation. Male and female rats became hypertensive when both kidneys were encapsulated with latex envelopes whether they were adrenalectomized two weeks prior to or at the time of kidney encapsulation. The type of hypertension produced in adrenalectomized rats did not differ from that of rats with intact adrenals with regard to time course of development of the elevated blood pressure (6–8 weeks), maximal elevation attained (190–220 mm Hg), polydipsia and hypertrophied hearts.

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