Urinary excretion of angiotensinogen in male and female Sprague Dawley rats during angiotensin II infusion and high salt diet

Q: What are the key findings of this study?

Candesartan reduced urinary angiotensinogen excretion during ANG II + high salt more effectively in female than male rats.

Q: What is the clinical evidence from this study?

Population: Angiotensin II-dependent hypertension (preclinical rat model) (n=37). Intervention: High salt diet, Angiotensin II infusion, and Candesartan vs. High salt diet alone, Angiotensin II alone, and Angiotensin II + high salt diet without Candesartan. Primary outcome: Urinary angiotensinogen excretion (uAGT, ng/day) measured by enzyme immunoassay (p=<0.01).

Q: What does this research mean for the field?

Candesartan reduces urinary angiotensinogen excretion induced by high salt and angiotensin II infusion more effectively in female rats than in male rats. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To determine whether high-salt intake and angiotensin II-dependent hypertension cause sexually dimorphic alterations in urinary angiotensinogen excretion.

Vicky F. Rands; Charlene Abadie Byrd; Dale M. Seth; Hiroyuki Kobori; Minolfa C. Prieto

doi:10.1096/fasebj.24.1_supplement.1024.28

April 1, 2010The FASEB Journal

Urinary excretion of angiotensinogen in male and female Sprague Dawley rats during angiotensin II infusion and high salt diet

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Key result

Candesartan suppresses urinary angiotensinogen excretion more effectively in female than male rats.

P<0.01
n=37

Why the study?

Urinary angiotensinogen excretion differs between male and female Sprague Dawley rats on a normal salt diet. Whether the effects of a high salt diet on urinary angiotensinogen excretion exhibit sexual dimorphism during angiotensin II-dependent hypertension was examined.

Does a high salt diet during angiotensin II-dependent hypertension and subsequent candesartan treatment exhibit sexual dimorphism in urinary angiotensinogen excretion in Sprague Dawley rats?

Key Points

To determine whether high-salt intake and angiotensin II-dependent hypertension cause sexually dimorphic alterations in urinary angiotensinogen excretion.
Studied 8-week-old male (n=20) and female (n=17) Sprague Dawley rats assigned to four groups: 8% NaCl high-salt diet, subcutaneous angiotensin II infusion (80 ng/min for 14 days), angiotensin II plus high salt, or angiotensin II plus high salt with candesartan (25 mg/L in drinking water).
Quantified urinary angiotensinogen excretion rates across groups using enzyme immunoassay.
High-salt diet alone did not raise excretion above baseline, whereas angiotensin II infusion increased urinary angiotensinogen significantly more in males than females (1107±1061 vs. 206±74 ng/day, p<0.01); combined high salt and angiotensin II further elevated levels in both (males: 4363±1673 vs. females: 8022±1300 ng/day, p=ns).
Candesartan treatment ameliorated urinary angiotensinogen augmentation in both sexes, achieving significantly greater suppression in females than in males (10±4 vs. 240±28 ng/day, p<0.01).

Structured PICO

Does a high salt diet during angiotensin II-dependent hypertension and subsequent candesartan treatment exhibit sexual dimorphism in urinary angiotensinogen excretion in Sprague Dawley rats?

P

Population

37 age-matched (8-week-old) male (n=20) and female (n=17) Sprague Dawley rats studied over 14 days of angiotensin II infusion and high salt diet.

I

Intervention

Four experimental groups over 14 days: 1) High salt diet (HS; 8% NaCl); 2) Angiotensin II (ANG II; 80 ng/min subcutaneously for 14 days); 3) ANG II + HS; 4) ANG II + HS + candesartan (25 mg/L in drinking water)

C

Comparator

Comparison between male and female rats across baseline normal salt diet, HS diet alone, ANG II infusion, ANG II + HS, and ANG II + HS + candesartan groups

O

Outcome

Urinary angiotensinogen excretion rate (uAGT, ng/day) measured by enzyme immunoassaysurrogate

Main Result

p-value: p=<0.01

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Implication

Demonstrates sexual dimorphism in urinary angiotensinogen excretion in Sprague Dawley rats, with males having higher baseline and HS levels, while female hypertensive rats experience more effective attenuation of ANG II + HS-induced uAGT elevation with candesartan.

Abstract

We have found that urinary angiotensinogen (AGT) excretion (uAGT) differs between male(♂)and female(♀) Sprague Dawley (SD) rats on a normal salt diet (♂: 60±26 vs ♀: 4.5 ±0.2ng/day, p<0.05). In this study, we examined if the effects of a high salt (HS) diet on uAGT exhibits sexual dimorphism during Angiotensin (ANG) II dependent hypertension. Four groups of age‐matched (8 weeks) male (n= 20) and female (n=17) SD rats were studied: 1) high salt diet (HS; 8%NaCl); 2) ANG II (80ng/min, sc; for 14 days); 3) ANG II + HS; 4) ANG II + HS + Candesartan. (CAND, 25 mg/L in drinking water). uAGT levels were measured by enzyme immunoassay. HS diet alone did not raise uAGT levels (♂: 107±23 vs. ♀: 5±2ng/day) from baseline; however, AGT increased significantly during ANG II infusion (♂: 1107±1061 vs ♀: 206±74ng/day, p<0.01) and was augmented even further in ANG II + HS (♂: 4363±1673 vs. ♀: 8022±1300ng/day, p=ns). Candesartan ameliorated this effect with a better response in female than in male rats.(♂: 240±28 vs. ♀: 10±4 ng/day, p< 0.01). The results demonstrate a sexual dimorphism in the uAGT excretion rate during baseline conditions and HS diet characterized by higher levels in the males. The augmentation of uAGT with HS + ANG II is ameliorated more effectively by ARB treatment in female ANG II hypertensive rats than in males.

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Cite This Study

Rands et al. (2010) studied Angiotensin II-dependent hypertension (preclinical rat model) (n=37). High salt diet, Angiotensin II infusion, and Candesartan vs. High salt diet alone, Angiotensin II alone, and Angiotensin II + high salt diet without Candesartan was evaluated on Urinary angiotensinogen excretion (uAGT, ng/day) measured by enzyme immunoassay (p=<0.01). Candesartan reduced urinary angiotensinogen excretion during ANG II + high salt more effectively in female than male rats.

synapsesocial.com/papers/6af3e6c1dd350e4563eb248b https://doi.org/10.1096/fasebj.24.1_supplement.1024.28

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Urinary excretion of angiotensinogen in male and female Sprague Dawley rats during angiotensin II infusion and high salt diet

Key Points

Structured PICO

Main Result

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Urinary excretion of angiotensinogen in male and female Sprague Dawley rats during angiotensin II infusion and high salt diet

Key Points

Structured PICO

Main Result

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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