ET-1 actions in the kidney: Evidence for sex differences

W. Kittikulsuth, Jennifer C Sullivan, David M. Pollock

Research output: Contribution to journalReview article

32 Citations (Scopus)

Abstract

Hypertension and chronic kidney disease are more common in men than in premenopausal women at the same age. In animal models, females are relatively protected against genetic or pharmacological procedures that produce high blood pressure and renal injury. Overactivation or dysfunction of the endothelin (ET) system modulates the progression of hypertension or kidney diseases with the ETA receptor primarily mediating vasoconstriction, injury and anti-natriuresis, and ETB receptors having opposite effects. The purpose of this review is to examine the role of the ET system in the kidney with a focus on the inequality between the sexes associated with the susceptibility to and progression of hypertension and kidney diseases. In most animal models, males have higher renal ET-1 mRNA expression, greater ET A-mediated responses, including renal medullary vasoconstriction, and increased renal injury. These differences are reduced following gonadectomy suggesting a role for sex hormones, mainly testosterone. In contrast, females are relatively protected from high blood pressure and kidney damage via increased ETB versus ETA receptor function. Furthermore, ETA receptors may have a favourable effect on sodium excretion and reducing renal damage in females. In human studies, the genetic polymorphisms of the ET system are more associated with hypertension and renal injury in women. However, the knowledge of sex differences in the efficacy or adverse events of ETA antagonists in the treatment of hypertension and kidney disease is poorly described. Increased understanding how the ET system acts differently in the kidneys between sexes, especially with regard to receptor subtype function, could lead to better treatments for hypertension and renal disease. LINKED ARTICLES This article is part of a themed section on Endothelin. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.168. issue-1

Original languageEnglish (US)
Pages (from-to)318-326
Number of pages9
JournalBritish Journal of Pharmacology
Volume168
Issue number2
DOIs
StatePublished - Jan 1 2013

Fingerprint

Endothelin-1
Sex Characteristics
Endothelins
Kidney
Hypertension
Kidney Diseases
Renal Hypertension
Wounds and Injuries
Vasoconstriction
Animal Models
Natriuresis
Medical Genetics
Gonadal Steroid Hormones
Genetic Polymorphisms
Chronic Renal Insufficiency
Testosterone
Sodium
Pharmacology
Messenger RNA
Therapeutics

Keywords

  • ET-1
  • hypertension
  • kidney
  • renal injury
  • renal medulla
  • sex

ASJC Scopus subject areas

  • Pharmacology

Cite this

ET-1 actions in the kidney : Evidence for sex differences. / Kittikulsuth, W.; Sullivan, Jennifer C; Pollock, David M.

In: British Journal of Pharmacology, Vol. 168, No. 2, 01.01.2013, p. 318-326.

Research output: Contribution to journalReview article

Kittikulsuth, W. ; Sullivan, Jennifer C ; Pollock, David M. / ET-1 actions in the kidney : Evidence for sex differences. In: British Journal of Pharmacology. 2013 ; Vol. 168, No. 2. pp. 318-326.
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