Nitric Oxide Donors as Potential Drugs for the Treatment of Vascular Diseases Due to Endothelium Dysfunction
| Autor: | Daniela Esteves Ferreira dos Reis Costa, Michele Paulo, Daniella Bonaventura, Lusiane Maria Bendhack, Claure N. Lunardi |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Vascular smooth muscle
Endothelium Nitric Oxide Synthase Type III Vasodilation 030204 cardiovascular system & hematology Pharmacology Nitric Oxide Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Enos Drug Discovery medicine Humans Nitric Oxide Donors Vascular Diseases Endothelial dysfunction 030304 developmental biology 0303 health sciences biology Endothelial Cells Tetrahydrobiopterin biology.organism_classification medicine.disease medicine.anatomical_structure chemistry Pharmaceutical Preparations Endothelium Vascular Soluble guanylyl cyclase medicine.drug |
| Zdroj: | Current pharmaceutical design. 26(30) |
| ISSN: | 1873-4286 |
| Popis: | Endothelial dysfunction and consequent vasoconstriction are a common condition in patients with hypertension and other cardiovascular diseases. Endothelial cells produce and release vasodilator substances that play a pivotal role in normal vascular tone. The mechanisms underlying endothelial dysfunction are multifactorial. However, enhanced reactive oxygen species (ROS) production and consequent vasoconstriction instead of endothelium-derived relaxant generation and consequent vasodilatation contribute to this dysfunction considerably. The main targets of the drugs that are currently used to treat vascular diseases concerning enzyme activities and protein functions that are impaired by endothelial nitric oxide synthase (eNOS) uncoupling and ROS production. Nitric oxide (NO) bioavailability can decrease due to deficient NO production by eNOS and/or NO release to vascular smooth muscle cells, which impairs endothelial function. Considering the NO cellular mechanisms, tackling the issue of eNOS uncoupling could avoid endothelial dysfunction: provision of the enzyme cofactor tetrahydrobiopterin (BH4) should elicit NO release from NO donors, to activate soluble guanylyl cyclase. This should increase cyclic guanosine-monophosphate (cGMP) generation and inhibit phosphodiesterases (especially PDE5) that selectively degrade cGMP. Consequently, protein kinase-G should be activated, and K+ channels should be phosphorylated and activated, which is crucial for cell membrane hyperpolarization and vasodilation and/or inhibition of ROS production. The present review summarizes the current concepts about the vascular cellular mechanisms that underlie endothelial dysfunction and which could be the target of drugs for the treatment of patients with cardiovascular disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|