Extracellular signal-regulated kinase 1/2 activation, via downregulation of mitogen-activated protein kinase phosphatase 1, mediates sex differences in desoxycorticosterone acetate-salt hypertension vascular reactivity

Fernanda R. Giachini, Jennifer C Sullivan, Victor V. Lima, Fernando S. Carneiro, Zuleica B. Fortes, David M. Pollock, Maria Helena C. Carvalho, R Clinton Webb, Rita C. Tostes

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Extracellular signal-regulated kinase (ERK)1/2 has been reported to play a role in vascular dysfunction associated with mineralocorticoid hypertension. We hypothesized that, compared with female rats, an upregulation of ERK1/2 signaling in the vasculature of male rats contributes to augmented contractile responses in mineralocorticoid hypertension. Uninephrectomized male and female Sprague-Dawley rats received desoxycorticosterone acetate (DOCA) pellets (200 mg per animal) and saline to drink for 3 weeks. Control uninephrectomized rats received tap water to drink. Blood pressure, measured by telemetry, was significantly higher in male DOCA rats (191±3 mm Hg) compared with female DOCA rats (172±7 mm Hg; n=5). DOCA treatment resulted in augmented contractile responses to phenylephrine in aorta (22±3 mN; n=6) and small mesenteric arteries (13±2 mN; n=6) from male DOCA rats versus uninephrectomized male rats (16±3 and 10±2 mN, respectively; P<0.05) and female DOCA rats (15±1 and 11±1 mN, respectively). ERK1/2 inhibition with PD-98059 (10 μmol/L) abrogated increased contraction to phenylephrine in aorta (14±2 mN) and small mesenteric arteries (10±2 mN) from male DOCA rats, without any effects in arteries from male uninephrectomized or female animals. Compared with the other groups, phosphorylated ERK1/2 levels were increased in the aorta from male DOCA rats, whereas mitogen-activated protein kinase phosphatase 1 expression was decreased. Interleukin-10 plasma levels, which positively regulate mitogen-activated protein kinase phosphatase 1 activity, were reduced in male DOCA-salt rats. We speculate that augmented vascular reactivity in male hypertensive rats is mediated via activation of the ERK1/2 pathway. In addition, mitogen-activated protein kinase phosphatase 1 and interleukin 10 play regulatory roles in this process.

Original languageEnglish (US)
Pages (from-to)172-179
Number of pages8
JournalHypertension
Volume55
Issue number1
DOIs
StatePublished - Jan 1 2010

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Mitogen-Activated Protein Kinase Phosphatases
Dual Specificity Phosphatase 1
Desoxycorticosterone Acetate
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Sex Characteristics
Blood Vessels
Down-Regulation
Salts
Hypertension
Aorta
Mineralocorticoids
Mesenteric Arteries
Phenylephrine
Interleukin-10
Telemetry
MAP Kinase Signaling System

Keywords

  • ERK1/2
  • Hypertension
  • MKP-1
  • Sex differences
  • Vascular reactivity

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Extracellular signal-regulated kinase 1/2 activation, via downregulation of mitogen-activated protein kinase phosphatase 1, mediates sex differences in desoxycorticosterone acetate-salt hypertension vascular reactivity. / Giachini, Fernanda R.; Sullivan, Jennifer C; Lima, Victor V.; Carneiro, Fernando S.; Fortes, Zuleica B.; Pollock, David M.; Carvalho, Maria Helena C.; Webb, R Clinton; Tostes, Rita C.

In: Hypertension, Vol. 55, No. 1, 01.01.2010, p. 172-179.

Research output: Contribution to journalArticle

Giachini, Fernanda R. ; Sullivan, Jennifer C ; Lima, Victor V. ; Carneiro, Fernando S. ; Fortes, Zuleica B. ; Pollock, David M. ; Carvalho, Maria Helena C. ; Webb, R Clinton ; Tostes, Rita C. / Extracellular signal-regulated kinase 1/2 activation, via downregulation of mitogen-activated protein kinase phosphatase 1, mediates sex differences in desoxycorticosterone acetate-salt hypertension vascular reactivity. In: Hypertension. 2010 ; Vol. 55, No. 1. pp. 172-179.
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