Influence of the selective COX-2 inhibitor celecoxib on sex differences in blood pressure and albuminuria in spontaneously hypertensive rats

Ahmed Abdelrazik Elmarakby, Mohamed Katary, Jennifer S. Pollock, Jennifer C Sullivan

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3 Citations (Scopus)

Abstract

We previously reported that female spontaneously hypertensive rats (SHR) have greater cyclooxygenase-2 (COX-2) expression in the renal medulla and enhanced urinary excretion of prostaglandin (PG) E2 (PGE2) metabolites compared to male SHR. Based on the role of COX-2-derived prostanoids in the regulation of cardiovascular health, the aim of the current study was to test the hypothesis that blood pressure (BP) in female SHR is more sensitive to COX-2 inhibition than in males. Seven week old male and female SHR were implanted with telemetry transmitters for continuous BP recording. After one week of baseline BP recording, male and female SHR were randomized to receive the selective COX-2 inhibitor celecoxib (10 mg/kg/day) or vehicle for six weeks (from 9 to 14 weeks of age). Female SHR had lower BP and albuminuria compared to male SHR as well as enhanced urinary excretion of PGE metabolite (PGEM), 6-keto PGF and thromboxane B2, indicators of PGE2, PGI2 and TXA2, respectively. Treatment with celecoxib did not significantly alter BP or albuminuria in either female or male SHR. Celecoxib did not change PGs metabolites excretion in male SHR; however, excretion levels of PGEM and 6-keto PGF were reduced in female SHR. COX-2 derived PG can also induce oxidative stress. Markers of oxidative stress (thiobarbituric acid reactive substances (TBARs) and H2O2 excretion) were lesser in female SHR versus male SHR. Celecoxib treatment did not significantly change markers of oxidative stress in female SHR, however, urinary TBARs excretion was significantly reduced in male SHR after 6 weeks of treatment with celecoxib. Therefore, although celecoxib treatment appears to have distinct effects on prostanoids levels in female SHR vs. males, it is unlikely that COX-2 contributes to established sex differences in BP in SHR.

Original languageEnglish (US)
Pages (from-to)16-20
Number of pages5
JournalProstaglandins and Other Lipid Mediators
Volume135
DOIs
StatePublished - Mar 1 2018

Fingerprint

Celecoxib
Albuminuria
Cyclooxygenase 2 Inhibitors
Blood pressure
Inbred SHR Rats
Sex Characteristics
Rats
Blood Pressure
Cyclooxygenase 2
Metabolites
Oxidative stress
Prostaglandins
Oxidative Stress
Thiobarbituric Acid Reactive Substances
Prostaglandins E

Keywords

  • Albuminuria
  • Blood pressure
  • Celecoxib
  • Oxidative stress
  • Prostaglandin metabolites
  • SHR
  • Sex difference

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

Cite this

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title = "Influence of the selective COX-2 inhibitor celecoxib on sex differences in blood pressure and albuminuria in spontaneously hypertensive rats",
abstract = "We previously reported that female spontaneously hypertensive rats (SHR) have greater cyclooxygenase-2 (COX-2) expression in the renal medulla and enhanced urinary excretion of prostaglandin (PG) E2 (PGE2) metabolites compared to male SHR. Based on the role of COX-2-derived prostanoids in the regulation of cardiovascular health, the aim of the current study was to test the hypothesis that blood pressure (BP) in female SHR is more sensitive to COX-2 inhibition than in males. Seven week old male and female SHR were implanted with telemetry transmitters for continuous BP recording. After one week of baseline BP recording, male and female SHR were randomized to receive the selective COX-2 inhibitor celecoxib (10 mg/kg/day) or vehicle for six weeks (from 9 to 14 weeks of age). Female SHR had lower BP and albuminuria compared to male SHR as well as enhanced urinary excretion of PGE metabolite (PGEM), 6-keto PGF1α and thromboxane B2, indicators of PGE2, PGI2 and TXA2, respectively. Treatment with celecoxib did not significantly alter BP or albuminuria in either female or male SHR. Celecoxib did not change PGs metabolites excretion in male SHR; however, excretion levels of PGEM and 6-keto PGF1α were reduced in female SHR. COX-2 derived PG can also induce oxidative stress. Markers of oxidative stress (thiobarbituric acid reactive substances (TBARs) and H2O2 excretion) were lesser in female SHR versus male SHR. Celecoxib treatment did not significantly change markers of oxidative stress in female SHR, however, urinary TBARs excretion was significantly reduced in male SHR after 6 weeks of treatment with celecoxib. Therefore, although celecoxib treatment appears to have distinct effects on prostanoids levels in female SHR vs. males, it is unlikely that COX-2 contributes to established sex differences in BP in SHR.",
keywords = "Albuminuria, Blood pressure, Celecoxib, Oxidative stress, Prostaglandin metabolites, SHR, Sex difference",
author = "Elmarakby, {Ahmed Abdelrazik} and Mohamed Katary and Pollock, {Jennifer S.} and Sullivan, {Jennifer C}",
year = "2018",
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doi = "10.1016/j.prostaglandins.2018.02.002",
language = "English (US)",
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pages = "16--20",
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TY - JOUR

T1 - Influence of the selective COX-2 inhibitor celecoxib on sex differences in blood pressure and albuminuria in spontaneously hypertensive rats

AU - Elmarakby, Ahmed Abdelrazik

AU - Katary, Mohamed

AU - Pollock, Jennifer S.

AU - Sullivan, Jennifer C

PY - 2018/3/1

Y1 - 2018/3/1

N2 - We previously reported that female spontaneously hypertensive rats (SHR) have greater cyclooxygenase-2 (COX-2) expression in the renal medulla and enhanced urinary excretion of prostaglandin (PG) E2 (PGE2) metabolites compared to male SHR. Based on the role of COX-2-derived prostanoids in the regulation of cardiovascular health, the aim of the current study was to test the hypothesis that blood pressure (BP) in female SHR is more sensitive to COX-2 inhibition than in males. Seven week old male and female SHR were implanted with telemetry transmitters for continuous BP recording. After one week of baseline BP recording, male and female SHR were randomized to receive the selective COX-2 inhibitor celecoxib (10 mg/kg/day) or vehicle for six weeks (from 9 to 14 weeks of age). Female SHR had lower BP and albuminuria compared to male SHR as well as enhanced urinary excretion of PGE metabolite (PGEM), 6-keto PGF1α and thromboxane B2, indicators of PGE2, PGI2 and TXA2, respectively. Treatment with celecoxib did not significantly alter BP or albuminuria in either female or male SHR. Celecoxib did not change PGs metabolites excretion in male SHR; however, excretion levels of PGEM and 6-keto PGF1α were reduced in female SHR. COX-2 derived PG can also induce oxidative stress. Markers of oxidative stress (thiobarbituric acid reactive substances (TBARs) and H2O2 excretion) were lesser in female SHR versus male SHR. Celecoxib treatment did not significantly change markers of oxidative stress in female SHR, however, urinary TBARs excretion was significantly reduced in male SHR after 6 weeks of treatment with celecoxib. Therefore, although celecoxib treatment appears to have distinct effects on prostanoids levels in female SHR vs. males, it is unlikely that COX-2 contributes to established sex differences in BP in SHR.

AB - We previously reported that female spontaneously hypertensive rats (SHR) have greater cyclooxygenase-2 (COX-2) expression in the renal medulla and enhanced urinary excretion of prostaglandin (PG) E2 (PGE2) metabolites compared to male SHR. Based on the role of COX-2-derived prostanoids in the regulation of cardiovascular health, the aim of the current study was to test the hypothesis that blood pressure (BP) in female SHR is more sensitive to COX-2 inhibition than in males. Seven week old male and female SHR were implanted with telemetry transmitters for continuous BP recording. After one week of baseline BP recording, male and female SHR were randomized to receive the selective COX-2 inhibitor celecoxib (10 mg/kg/day) or vehicle for six weeks (from 9 to 14 weeks of age). Female SHR had lower BP and albuminuria compared to male SHR as well as enhanced urinary excretion of PGE metabolite (PGEM), 6-keto PGF1α and thromboxane B2, indicators of PGE2, PGI2 and TXA2, respectively. Treatment with celecoxib did not significantly alter BP or albuminuria in either female or male SHR. Celecoxib did not change PGs metabolites excretion in male SHR; however, excretion levels of PGEM and 6-keto PGF1α were reduced in female SHR. COX-2 derived PG can also induce oxidative stress. Markers of oxidative stress (thiobarbituric acid reactive substances (TBARs) and H2O2 excretion) were lesser in female SHR versus male SHR. Celecoxib treatment did not significantly change markers of oxidative stress in female SHR, however, urinary TBARs excretion was significantly reduced in male SHR after 6 weeks of treatment with celecoxib. Therefore, although celecoxib treatment appears to have distinct effects on prostanoids levels in female SHR vs. males, it is unlikely that COX-2 contributes to established sex differences in BP in SHR.

KW - Albuminuria

KW - Blood pressure

KW - Celecoxib

KW - Oxidative stress

KW - Prostaglandin metabolites

KW - SHR

KW - Sex difference

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