The CUL3/KLHL3-WNK-SPAK/OSR1 pathway as a target for antihypertensive therapy

Mohammed Z. Ferdaus, James (Jim) McCormick

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Chronic high blood pressure (hypertension) is the most common disease in the Unites States. While several classes of drugs exist to treat it, many patients (up to 10 million Americans) respond poorly to therapy, even when multiple classes are used. Recent evidence suggests that a significant portion of patients will always remain hypertensive despite maximum therapy with the drugs currently available. Therefore, there is a pressing need to develop novel antihypertensive agents. One limitation has been the identification of new targets, a limitation that has been overcome by recent insights into the mechanisms underlying monogenic forms of hypertension. The disease familial hyperkalemic hypertension is caused by mutations in with-no-lysine (WNK) kinases 1 and 4 and in cullin-3 and kelch-like 3, components of an E3 ubiquitin ligase complex that promotes WNK kinase degradation. The study of the mechanisms by which this pathway regulates blood pressure has identified several candidates for the development of new antihypertensive agents. This pathway is particularly attractive since its inhibition may not only reduce renal sodium reabsorption along multiple segments but may also reduce vascular tone. Here, we will describe the mechanisms by which this pathway regulate blood pressure and discuss the potential of targeting it to develop new antihypertensive drugs.

Original languageEnglish (US)
Pages (from-to)F1389-F1396
JournalAmerican Journal of Physiology - Renal Physiology
Volume310
Issue number11
DOIs
StatePublished - Jun 1 2016

Fingerprint

Antihypertensive Agents
Hypertension
Phosphotransferases
Cullin Proteins
Blood Pressure
Ubiquitin-Protein Ligases
Therapeutics
Lysine
Blood Vessels
Sodium
Drug Therapy
Mutation
Pharmaceutical Preparations

Keywords

  • Drugs
  • Hypertension
  • Kinases
  • Na-Cl cotransporter

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

The CUL3/KLHL3-WNK-SPAK/OSR1 pathway as a target for antihypertensive therapy. / Ferdaus, Mohammed Z.; McCormick, James (Jim).

In: American Journal of Physiology - Renal Physiology, Vol. 310, No. 11, 01.06.2016, p. F1389-F1396.

Research output: Contribution to journalArticle

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