Heme-dependent and independent soluble guanylate cyclase activators and vasodilation

Fernanda B.M. Priviero, R. Clinton Webb

Research output: Contribution to journalReview article

29 Scopus citations

Abstract

Since the discovery of nitric oxide (NO), which is released from endothelial cells as the main mediator of vasodilation, its target, the soluble guanylyl cyclase (sGC), has become a focus of interest for the treatment of diseases associated with endothelial dysfunction. NO donors were developed to suppress NO deficiency; however, tolerance to organic nitrates was reported. Non-NO-based drugs targeting sGC were developed to overcome the problem of tolerance. In this review, we briefly describe the process of sGC activation by its main physiological activator NO and the advances in the development of drugs capable of activating sGC in a NO-independent manner. sGC stimulators, as some of these drugs are called, require the integrity of the reduced heme moiety of the prosthetic group within the sGC and therefore are called heme-dependent stimulators. Other drugs are able to activate sGC independent of heme moiety and are hence called heme-independent activators. Because pathologic conditions modulate sGC and oxidize the heme moiety, the heme-independent sGC activators could potentially become drugs of choice because of their higher affinity to the oxidized enzyme. However, these drugs are still undergoing clinical trials and are not available for clinical use.

Original languageEnglish (US)
Pages (from-to)229-233
Number of pages5
JournalJournal of Cardiovascular Pharmacology
Volume56
Issue number3
DOIs
StatePublished - Sep 2010

Keywords

  • endothelial dysfunction
  • nitric oxide
  • soluble guanylyl cyclase activators
  • vascular disease
  • vascular smooth muscle

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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