Sulodexide Promotes Arterial Relaxation via Endothelium-Dependent Nitric Oxide-Mediated Pathway
| Autor: | Joseph D. Raffetto, Paolo Mattana, Raouf A. Khalil, Fiorella Calanni |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Contraction (grammar) Vascular smooth muscle Endothelium Pharmacology Nitric Oxide Biochemistry Article Nitric oxide Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Organ Culture Techniques medicine.artery medicine Animals Phenylephrine Glycosaminoglycans Aorta biology Dose-Response Relationship Drug Chemistry Anticoagulants Hyperpolarization (biology) Rats Nitric oxide synthase Vasodilation 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis cardiovascular system biology.protein Endothelium Vascular medicine.drug Signal Transduction |
| Zdroj: | Biochem Pharmacol |
| Popis: | Sulodexide (SDX) is a highly purified glycosaminoglycan with antithrombotic and profibrinolytic properties and reported benefits in thrombotic and atherosclerotic vascular disorders. However, the effects of SDX on vascular function are unclear. We tested whether SDX affects vascular relaxation and examined the potential underlying mechanisms. Isolated segments of male rat abdominal aorta and mesenteric artery were suspended in a tissue bath, and the changes in arterial contraction/relaxation were measured. The α-adrenergic receptor agonist phenylephrine (Phe) (10(−9) to 10(−5) M) caused concentration-dependent aortic and mesenteric artery contraction that was reduced in tissues pretreated with SDX (1 mg/ml). In aortic and mesenteric arterial segments precontracted with submaximal concentration of Phe (3×10(−7) to 6×10(−7) M), SDX (0.001 to 1 mg/ml) caused concentration-dependent relaxation. To test the role of endothelium, SDX-induced relaxation was compared with that of acetylcholine (ACh), a known activator of endothelium-dependent relaxation. In Phe precontracted aorta, ACh relaxation was abolished and SDX relaxation was significantly inhibited by endothelium removal or the nitric oxide synthase (NOS) inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME), suggesting a role of NO. In mesenteric artery, ACh relaxation was abolished by endothelium removal, partially blocked by L-NAME, and completely blocked by a mixture of indomethacin, a cyclooxygenase inhibitor and blocker of the PGI(2)-cAMP pathway, and tetraethylammonium, a blocker of K(+) channels and EDHF-dependent hyperpolarization pathway. In comparison, SDX relaxation of mesenteric artery was almost completely inhibited by endothelium removal or NOS inhibitor L-NAME. SDX enhanced vascular relaxation and increased nitrate/nitrite production in response to all ACh concentrations in the aorta, but only to low ACh concentrations ( |
| Databáze: | OpenAIRE |
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