Short-term activation by low 17β-estradiol concentrations of the Na+/H+ exchanger in rat aortic smooth muscle cells: Physiopathological implications

Sandra Incerpi, Silvia D'Arezzo, Maria Marino, Roberto Musanti, Valentina Pallottini, Andrea Pascolini, Anna Trentalance

Research output: Contribution to journalArticle

Abstract

Low physiological concentrations of 17β-estradiol increased the intracellular pH of rat aortic smooth muscle cells by a rapid nongenomic mechanism. This effect was due to stimulation of the Na+/H + exchanger activity, measured using the intracellular pH-sensitive fluorescent probe 2′,7′ -bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein. The 17β-estradiol gave rise to a bell-shaped dose response, with a maximum at 10-12 M and no significant effect at 10-9 M. The specificity of the effect was verified by the use of the Na+/H+ exchanger inhibitor 5-(ethyl-N-isopropyl)amiloride and the lack of effect of the isomer 17α-estradiol. Inhibitors of the nuclear estrogen receptors, tamoxifen and ICI 182,780, completely prevented activation of the exchanger by 17β-estradiol. The effect of low estrogen concentrations on the intracellular pH was mimicked by both norepinephrine and phenylephrine, suggesting a connection between the increase of intracellular pH and the muscle contraction process. The transduction mechanism for this nongenomic effect of estrogens did not involve modulation of the cAMP content, whereas inositol 1,4,5-trisphosphate, protein kinase C and MAPK pathways appear to play a role, as indicated by both pharmacological approaches and immunoblot experiments on protein kinase C translocation and ERK phosphorylation. These results for the first time provide evidence for a nongenomic effect of low physiological concentrations of 17β-estradiol on intracellular pH that, together with other factors, may contribute to the development of hypertension and atherosclerosis in men and postmenopausal women and increase the risk of cardiovascular disease. Paradoxically, the lack of stimulation at high physiological estradiol levels could explain the protective effects found in premenopausal women.

Original languageEnglish
Pages (from-to)4315-4324
Number of pages10
JournalEndocrinology
Volume144
Issue number10
DOIs
Publication statusPublished - Oct 1 2003

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Sodium-Hydrogen Antiporter
Smooth Muscle Myocytes
Estradiol
Protein Kinase C
Estrogens
Inositol 1,4,5-Trisphosphate
Amiloride
Phenylephrine
Tamoxifen
Muscle Contraction
Fluorescent Dyes
Estrogen Receptors
Atherosclerosis
Norepinephrine
Cardiovascular Diseases
Phosphorylation
Pharmacology
Hypertension

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Short-term activation by low 17β-estradiol concentrations of the Na+/H+ exchanger in rat aortic smooth muscle cells : Physiopathological implications. / Incerpi, Sandra; D'Arezzo, Silvia; Marino, Maria; Musanti, Roberto; Pallottini, Valentina; Pascolini, Andrea; Trentalance, Anna.

In: Endocrinology, Vol. 144, No. 10, 01.10.2003, p. 4315-4324.

Research output: Contribution to journalArticle

Incerpi, Sandra ; D'Arezzo, Silvia ; Marino, Maria ; Musanti, Roberto ; Pallottini, Valentina ; Pascolini, Andrea ; Trentalance, Anna. / Short-term activation by low 17β-estradiol concentrations of the Na+/H+ exchanger in rat aortic smooth muscle cells : Physiopathological implications. In: Endocrinology. 2003 ; Vol. 144, No. 10. pp. 4315-4324.
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