Mechanisms of Disease: The tissue kallikrein-kinin system in hypertension and vascular remodeling

Paolo Madeddu, Costanza Emanueli, Samir El-Dahr

Research output: Contribution to journalArticlepeer-review


The pathogenesis of arterial hypertension often involves a rise in systemic vascular resistance (vasoconstriction and vascular remodeling) and impairment of salt excretion in the kidney (inappropriate salt retention despite elevated blood pressure). Experimental and clinical evidence implicate an imbalance between endogenous vasoconstrictor and vasodilator systems in the development and maintenance of hypertension. Kinins (bradykinin and lys-bradykinin) are endogenous vasodilators and natriuretic peptides known best for their ability to antagonize angiotensin-induced vasoconstriction and sodium retention. In humans, angiotensin-converting enzyme inhibitors, a potent class of antihypertensive agents, lower blood pressure at least partially by favoring enhanced kinin accumulation in plasma and target tissues. The beneficial actions of kinins in renal and cardiovascular disease are largely mediated by nitric oxide and prostaglandins, and extend beyond their recognized role in lowering blood pressure to include cardioprotection and nephroprotection. This article is a review of exciting, recently generated genetic, biochemical and clinical data from studies that have examined the importance of the tissue kallikrein-kinin system in protection from hypertension, vascular remodeling and renal fibrosis. Development of novel therapeutic approaches to bolster kinin activity in the vascular wall and in specific compartments in the kidney might be a highly effective strategy for the treatment of hypertension and its complications, including cardiac hypertrophy and renal failure.

Original languageEnglish
Pages (from-to)208-221
Number of pages14
JournalNature Clinical Practice Nephrology
Issue number4
Publication statusPublished - Apr 2007


  • Angiotensin
  • Bradykinin
  • Cardiovascular
  • Kallikrein
  • Kidney

ASJC Scopus subject areas

  • Nephrology


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