Female spontaneously hypertensive rats are more dependent on ANG (1-7) to mediate effects of low-dose AT1 receptor blockade than males

Margaret A. Zimmerman, Ryan A. Harris, Jennifer C. Sullivan

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11 Citations (Scopus)

Abstract

ANG (1-7) contributes to the blood pressure (BP)-lowering effect of angiotensin receptor blockers (ARBs) in male experimental animals. Females have greater ANG (1-7) concentrations than males; however, the contribution of ANG (1-7) to ARB-mediated decreases in BP in females is unknown. The current study tested the hypothesis that female spontaneously hypertensive rats (SHR) have a larger ANG (1-7) contribution to the BP-lowering effects of the ARB candesartan than male SHR. Twelve-week-old male and female SHR were randomized to receive candesartan (0.5 mg·kg-1·day-1; 7 days), candesartan plus ANG II (200 ng·kg-1·min-1; 7 days), the ANG (1-7) antagonist A-779 (48 μg·kg-1·h-1) plus candesartan and ANG II. Candesartan decreased basal BP in males and females (baseline vs. candesartan: 142 ± 2 vs. 122 ± 3 and 129 ± 1 vs. 115 ± 1 mmHg, respectively; P < 0.05); however, the decrease was greater in males. ANG II increased BP in males in the presence of candesartan (149 ± 2 mmHg; P < 0.05); candesartan blocked ANG II-induced increases in BP in females (116 ± 1 mmHg). Pretreatment with A-779 abolished candesartan-mediated decreases in BP in females, but not males. A-779 also exacerbated ANG II-induced proteinuria (26 ± 6 vs. 77 ± 11 μg·kg-1·day-1, respectively; P < 0.05) and nephrinuria (20 ± 5 vs. 202 ± 58 μg·kg-1·day-1, respectively; P < 0.05) in candesartan-treated female SHR, with no effect in males. In conclusion, females are more sensitive to the BP-lowering effect of ARBs during ANG II infusion, whereas males are more sensitive under basal conditions. In addition, ANG (1-7) has a greater contribution to ARB-mediated decreases in BP, protein, and nephrin excretion in females relative to males.

Original languageEnglish (US)
Pages (from-to)F1136-F1142
JournalAmerican Journal of Physiology - Renal Physiology
Volume306
Issue number10
DOIs
StatePublished - Jan 1 2014

Fingerprint

Inbred SHR Rats
Blood Pressure
Angiotensin Receptor Antagonists
7-Ala-angiotensin (1-7)
candesartan
Proteinuria
Blood Proteins

Keywords

  • ANG (1-7)
  • Blood pressure
  • Gender
  • Renin-angiotensin system
  • SHR

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

@article{44efe2eafbdf42bdbbe3a7c2834c538f,
title = "Female spontaneously hypertensive rats are more dependent on ANG (1-7) to mediate effects of low-dose AT1 receptor blockade than males",
abstract = "ANG (1-7) contributes to the blood pressure (BP)-lowering effect of angiotensin receptor blockers (ARBs) in male experimental animals. Females have greater ANG (1-7) concentrations than males; however, the contribution of ANG (1-7) to ARB-mediated decreases in BP in females is unknown. The current study tested the hypothesis that female spontaneously hypertensive rats (SHR) have a larger ANG (1-7) contribution to the BP-lowering effects of the ARB candesartan than male SHR. Twelve-week-old male and female SHR were randomized to receive candesartan (0.5 mg·kg-1·day-1; 7 days), candesartan plus ANG II (200 ng·kg-1·min-1; 7 days), the ANG (1-7) antagonist A-779 (48 μg·kg-1·h-1) plus candesartan and ANG II. Candesartan decreased basal BP in males and females (baseline vs. candesartan: 142 ± 2 vs. 122 ± 3 and 129 ± 1 vs. 115 ± 1 mmHg, respectively; P < 0.05); however, the decrease was greater in males. ANG II increased BP in males in the presence of candesartan (149 ± 2 mmHg; P < 0.05); candesartan blocked ANG II-induced increases in BP in females (116 ± 1 mmHg). Pretreatment with A-779 abolished candesartan-mediated decreases in BP in females, but not males. A-779 also exacerbated ANG II-induced proteinuria (26 ± 6 vs. 77 ± 11 μg·kg-1·day-1, respectively; P < 0.05) and nephrinuria (20 ± 5 vs. 202 ± 58 μg·kg-1·day-1, respectively; P < 0.05) in candesartan-treated female SHR, with no effect in males. In conclusion, females are more sensitive to the BP-lowering effect of ARBs during ANG II infusion, whereas males are more sensitive under basal conditions. In addition, ANG (1-7) has a greater contribution to ARB-mediated decreases in BP, protein, and nephrin excretion in females relative to males.",
keywords = "ANG (1-7), Blood pressure, Gender, Renin-angiotensin system, SHR",
author = "Zimmerman, {Margaret A.} and Harris, {Ryan A.} and Sullivan, {Jennifer C.}",
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T1 - Female spontaneously hypertensive rats are more dependent on ANG (1-7) to mediate effects of low-dose AT1 receptor blockade than males

AU - Zimmerman, Margaret A.

AU - Harris, Ryan A.

AU - Sullivan, Jennifer C.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - ANG (1-7) contributes to the blood pressure (BP)-lowering effect of angiotensin receptor blockers (ARBs) in male experimental animals. Females have greater ANG (1-7) concentrations than males; however, the contribution of ANG (1-7) to ARB-mediated decreases in BP in females is unknown. The current study tested the hypothesis that female spontaneously hypertensive rats (SHR) have a larger ANG (1-7) contribution to the BP-lowering effects of the ARB candesartan than male SHR. Twelve-week-old male and female SHR were randomized to receive candesartan (0.5 mg·kg-1·day-1; 7 days), candesartan plus ANG II (200 ng·kg-1·min-1; 7 days), the ANG (1-7) antagonist A-779 (48 μg·kg-1·h-1) plus candesartan and ANG II. Candesartan decreased basal BP in males and females (baseline vs. candesartan: 142 ± 2 vs. 122 ± 3 and 129 ± 1 vs. 115 ± 1 mmHg, respectively; P < 0.05); however, the decrease was greater in males. ANG II increased BP in males in the presence of candesartan (149 ± 2 mmHg; P < 0.05); candesartan blocked ANG II-induced increases in BP in females (116 ± 1 mmHg). Pretreatment with A-779 abolished candesartan-mediated decreases in BP in females, but not males. A-779 also exacerbated ANG II-induced proteinuria (26 ± 6 vs. 77 ± 11 μg·kg-1·day-1, respectively; P < 0.05) and nephrinuria (20 ± 5 vs. 202 ± 58 μg·kg-1·day-1, respectively; P < 0.05) in candesartan-treated female SHR, with no effect in males. In conclusion, females are more sensitive to the BP-lowering effect of ARBs during ANG II infusion, whereas males are more sensitive under basal conditions. In addition, ANG (1-7) has a greater contribution to ARB-mediated decreases in BP, protein, and nephrin excretion in females relative to males.

AB - ANG (1-7) contributes to the blood pressure (BP)-lowering effect of angiotensin receptor blockers (ARBs) in male experimental animals. Females have greater ANG (1-7) concentrations than males; however, the contribution of ANG (1-7) to ARB-mediated decreases in BP in females is unknown. The current study tested the hypothesis that female spontaneously hypertensive rats (SHR) have a larger ANG (1-7) contribution to the BP-lowering effects of the ARB candesartan than male SHR. Twelve-week-old male and female SHR were randomized to receive candesartan (0.5 mg·kg-1·day-1; 7 days), candesartan plus ANG II (200 ng·kg-1·min-1; 7 days), the ANG (1-7) antagonist A-779 (48 μg·kg-1·h-1) plus candesartan and ANG II. Candesartan decreased basal BP in males and females (baseline vs. candesartan: 142 ± 2 vs. 122 ± 3 and 129 ± 1 vs. 115 ± 1 mmHg, respectively; P < 0.05); however, the decrease was greater in males. ANG II increased BP in males in the presence of candesartan (149 ± 2 mmHg; P < 0.05); candesartan blocked ANG II-induced increases in BP in females (116 ± 1 mmHg). Pretreatment with A-779 abolished candesartan-mediated decreases in BP in females, but not males. A-779 also exacerbated ANG II-induced proteinuria (26 ± 6 vs. 77 ± 11 μg·kg-1·day-1, respectively; P < 0.05) and nephrinuria (20 ± 5 vs. 202 ± 58 μg·kg-1·day-1, respectively; P < 0.05) in candesartan-treated female SHR, with no effect in males. In conclusion, females are more sensitive to the BP-lowering effect of ARBs during ANG II infusion, whereas males are more sensitive under basal conditions. In addition, ANG (1-7) has a greater contribution to ARB-mediated decreases in BP, protein, and nephrin excretion in females relative to males.

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KW - Renin-angiotensin system

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