Sex differences in angiotensin-converting enzyme modulation of ang (1-7) levels in normotensive WKY rats

Kanchan Bhatia, Margaret A. Zimmerman, Jennifer C Sullivan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background Levels of the vasodilatory peptide angiotensin (Ang) (1-7) have been reported to be greater in females than in males, although the molecular mechanism responsible for this is unknown. Angiotensin-converting enzyme (ACE), ACE2, and neprilysin are key enzymes regulating Ang (1-7) formation. We conducted a study to determine the effect of sex on the activities of ACE, ACE2, and neprilysin in the kidneys of normotensive rats. We hypothesized that greater ACE2 or neprilysin activity in females would result in enhanced Ang (1-7) formation as compared with that in males. Methods We measured the enzymatic activities of ACE, ACE2, and neprilysin in the renal cortex and medulla of 12-week-old male and female WKY rats. We treated additional rats with vehicle or enalapril (10mg/kg/day in drinking water) for 14 days, and measured their Ang II and Ang (1-7) levels.RESULTSRenal cortical activity of ACE was greater in female than in male WKY rats (P < 0.05), but the activity of ACE in the renal medulla was not significantly different in the two sexes. Renal cortical and medullary ACE2 and neprilysin activities were comparable in male and female WKY rats. Treatment with enalapril significantly decreased Ang II levels in the renal cortex and medulla of male and female WKY rats as compared with those in vehicle-treated controls (P < 0.05); enalapril did not change the plasma levels of Ang II. Cortical levels of Ang (1-7) were higher in vehicle-treated females than in vehicle-treated males (P < 0.05), and treatment with enalapril decreased Ang (1-7) levels only in females (P < 0.05). Conclusions Our data supports a role for ACE in the formation of renal cortical Ang (1-7) in female WKY rats that is absent in males.

Original languageEnglish (US)
Pages (from-to)591-598
Number of pages8
JournalAmerican journal of hypertension
Volume26
Issue number5
DOIs
StatePublished - May 1 2013

Fingerprint

Inbred WKY Rats
Peptidyl-Dipeptidase A
Sex Characteristics
Neprilysin
Enalapril
Kidney
Angiotensin II
Angiotensins
angiotensin I (1-7)
Drinking Water
Peptides
Enzymes

Keywords

  • WKY
  • blood pressure
  • gender
  • hyptertension
  • kidney
  • renin-angiotensin system

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Sex differences in angiotensin-converting enzyme modulation of ang (1-7) levels in normotensive WKY rats. / Bhatia, Kanchan; Zimmerman, Margaret A.; Sullivan, Jennifer C.

In: American journal of hypertension, Vol. 26, No. 5, 01.05.2013, p. 591-598.

Research output: Contribution to journalArticle

@article{a58011174864477cad53fd6f26334b78,
title = "Sex differences in angiotensin-converting enzyme modulation of ang (1-7) levels in normotensive WKY rats",
abstract = "Background Levels of the vasodilatory peptide angiotensin (Ang) (1-7) have been reported to be greater in females than in males, although the molecular mechanism responsible for this is unknown. Angiotensin-converting enzyme (ACE), ACE2, and neprilysin are key enzymes regulating Ang (1-7) formation. We conducted a study to determine the effect of sex on the activities of ACE, ACE2, and neprilysin in the kidneys of normotensive rats. We hypothesized that greater ACE2 or neprilysin activity in females would result in enhanced Ang (1-7) formation as compared with that in males. Methods We measured the enzymatic activities of ACE, ACE2, and neprilysin in the renal cortex and medulla of 12-week-old male and female WKY rats. We treated additional rats with vehicle or enalapril (10mg/kg/day in drinking water) for 14 days, and measured their Ang II and Ang (1-7) levels.RESULTSRenal cortical activity of ACE was greater in female than in male WKY rats (P < 0.05), but the activity of ACE in the renal medulla was not significantly different in the two sexes. Renal cortical and medullary ACE2 and neprilysin activities were comparable in male and female WKY rats. Treatment with enalapril significantly decreased Ang II levels in the renal cortex and medulla of male and female WKY rats as compared with those in vehicle-treated controls (P < 0.05); enalapril did not change the plasma levels of Ang II. Cortical levels of Ang (1-7) were higher in vehicle-treated females than in vehicle-treated males (P < 0.05), and treatment with enalapril decreased Ang (1-7) levels only in females (P < 0.05). Conclusions Our data supports a role for ACE in the formation of renal cortical Ang (1-7) in female WKY rats that is absent in males.",
keywords = "WKY, blood pressure, gender, hyptertension, kidney, renin-angiotensin system",
author = "Kanchan Bhatia and Zimmerman, {Margaret A.} and Sullivan, {Jennifer C}",
year = "2013",
month = "5",
day = "1",
doi = "10.1093/ajh/hps088",
language = "English (US)",
volume = "26",
pages = "591--598",
journal = "American Journal of Hypertension",
issn = "0895-7061",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Sex differences in angiotensin-converting enzyme modulation of ang (1-7) levels in normotensive WKY rats

AU - Bhatia, Kanchan

AU - Zimmerman, Margaret A.

AU - Sullivan, Jennifer C

PY - 2013/5/1

Y1 - 2013/5/1

N2 - Background Levels of the vasodilatory peptide angiotensin (Ang) (1-7) have been reported to be greater in females than in males, although the molecular mechanism responsible for this is unknown. Angiotensin-converting enzyme (ACE), ACE2, and neprilysin are key enzymes regulating Ang (1-7) formation. We conducted a study to determine the effect of sex on the activities of ACE, ACE2, and neprilysin in the kidneys of normotensive rats. We hypothesized that greater ACE2 or neprilysin activity in females would result in enhanced Ang (1-7) formation as compared with that in males. Methods We measured the enzymatic activities of ACE, ACE2, and neprilysin in the renal cortex and medulla of 12-week-old male and female WKY rats. We treated additional rats with vehicle or enalapril (10mg/kg/day in drinking water) for 14 days, and measured their Ang II and Ang (1-7) levels.RESULTSRenal cortical activity of ACE was greater in female than in male WKY rats (P < 0.05), but the activity of ACE in the renal medulla was not significantly different in the two sexes. Renal cortical and medullary ACE2 and neprilysin activities were comparable in male and female WKY rats. Treatment with enalapril significantly decreased Ang II levels in the renal cortex and medulla of male and female WKY rats as compared with those in vehicle-treated controls (P < 0.05); enalapril did not change the plasma levels of Ang II. Cortical levels of Ang (1-7) were higher in vehicle-treated females than in vehicle-treated males (P < 0.05), and treatment with enalapril decreased Ang (1-7) levels only in females (P < 0.05). Conclusions Our data supports a role for ACE in the formation of renal cortical Ang (1-7) in female WKY rats that is absent in males.

AB - Background Levels of the vasodilatory peptide angiotensin (Ang) (1-7) have been reported to be greater in females than in males, although the molecular mechanism responsible for this is unknown. Angiotensin-converting enzyme (ACE), ACE2, and neprilysin are key enzymes regulating Ang (1-7) formation. We conducted a study to determine the effect of sex on the activities of ACE, ACE2, and neprilysin in the kidneys of normotensive rats. We hypothesized that greater ACE2 or neprilysin activity in females would result in enhanced Ang (1-7) formation as compared with that in males. Methods We measured the enzymatic activities of ACE, ACE2, and neprilysin in the renal cortex and medulla of 12-week-old male and female WKY rats. We treated additional rats with vehicle or enalapril (10mg/kg/day in drinking water) for 14 days, and measured their Ang II and Ang (1-7) levels.RESULTSRenal cortical activity of ACE was greater in female than in male WKY rats (P < 0.05), but the activity of ACE in the renal medulla was not significantly different in the two sexes. Renal cortical and medullary ACE2 and neprilysin activities were comparable in male and female WKY rats. Treatment with enalapril significantly decreased Ang II levels in the renal cortex and medulla of male and female WKY rats as compared with those in vehicle-treated controls (P < 0.05); enalapril did not change the plasma levels of Ang II. Cortical levels of Ang (1-7) were higher in vehicle-treated females than in vehicle-treated males (P < 0.05), and treatment with enalapril decreased Ang (1-7) levels only in females (P < 0.05). Conclusions Our data supports a role for ACE in the formation of renal cortical Ang (1-7) in female WKY rats that is absent in males.

KW - WKY

KW - blood pressure

KW - gender

KW - hyptertension

KW - kidney

KW - renin-angiotensin system

UR - http://www.scopus.com/inward/record.url?scp=84876550325&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876550325&partnerID=8YFLogxK

U2 - 10.1093/ajh/hps088

DO - 10.1093/ajh/hps088

M3 - Article

VL - 26

SP - 591

EP - 598

JO - American Journal of Hypertension

JF - American Journal of Hypertension

SN - 0895-7061

IS - 5

ER -