title: New Pharmacological Strategies to Increase cGMP.
abstract: The intracellular nucleotide cyclic guanosine monophosphate (cGMP) is found in many human organ tissues. Its concentration increases in response to the activation of receptor enzymes called guanylyl cyclases (GCs). Different ligands bind GCs, generating the second messenger cGMP, which in turn leads to a variety of biological actions. A deficit or dysfunction of this pathway at the cardiac, vascular, and renal levels manifests in cardiovascular diseases such as heart failure, arterial hypertension, and pulmonary arterial hypertension. An impairment of the cGMP pathway also may be involved in the pathogenesis of obesity as well as dementia. Therefore, agents enhancing the generation of cGMP for the treatment of these conditions have been intensively studied. Some have already been approved, and others are currently under investigation. This review discusses the potential of novel drugs directly or indirectly targeting cGMP as well as the progress of research to date.
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905; email: buglioni.alessia@mayo.edu , burnett.john@mayo.edu.
authors.forename: Alessia
authors.initials: A
authors.lastname: Buglioni
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905; email: buglioni.alessia@mayo.edu , burnett.john@mayo.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D001565:Benzoates / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis* / Q000172:deficiency; D020536:Enzyme Activators / Q000627:therapeutic use; D006162:Guanylate Cyclase / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008659:Metabolic Diseases / Q000188:drug therapy / Q000378:metabolism*; D045265:Natriuretic Peptides / Q000378:metabolism* / Q000627:therapeutic use; D015260:Neprilysin / Q000037:antagonists & inhibitors; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001565:Benzoates; D020536:Enzyme Activators; D008024:Ligands; D045265:Natriuretic Peptides; D010726:Phosphodiesterase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C480588:BAY 58-2667; D015260:Neprilysin; D006162:Guanylate Cyclase; D006152:Cyclic GMP; C542595:riociguat
keywords: NEP; NO; PDEs; cardiometabolic disease; guanylyl cyclase; natriuretic peptides