Pharmacological characterization of the vasodilating effect induced by the ruthenium complex cis-[Ru(NO)(NO2)(bpy)2].(PF6)2
| Autor: | Gerson Jhonatan Rodrigues, Amanda C. Pereira, Charles Chenwei Wang, Lusiane Maria Bendhack, Thiago Francisco De Moraes, Roberto Santana da Silva |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Vascular smooth muscle
Stereochemistry Vasodilator Agents chemistry.chemical_element Vasodilation Blood Pressure Nitric Oxide Muscle Smooth Vascular Nitric oxide chemistry.chemical_compound medicine Animals Nitrite Rats Wistar Aorta Pharmacology Dose-Response Relationship Drug Potassium channel blocker Nitroxyl Fluorescence humanities Ruthenium Rats chemistry Guanylate Cyclase Ruthenium Compounds Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Journal of cardiovascular pharmacology. 65(2) |
| ISSN: | 1533-4023 |
| Popis: | Nitric oxide (NO) can be found in different species and is a potent vasodilator. The ruthenium compound cis-[Ru(NO)(NO2)(bpy)2].(PF6)2 (BPY) can generate NO. This study aimed to investigate the BPY stability at physiological pH, the cellular mechanisms involved in BPY effect, NO species originating from BPY, and to verify how BPY affects blood pressure. Our results has shown that at pH 7.4 and 9.4, the NO coordinated to ruthenium (Ru-NO) is converted to nitrite (Ru-NO2) and remains stable. In aortic rings, the stable configuration of BPY (Ru-NO2) induces vascular relaxation in a concentration-dependent manner. Thus, further experiments were made with stable configuration of BPY (Ru-NO2). The relaxation induced by BPY was abolished in the presence of guanylyl cyclase inhibitor and decreased in the presence of potassium channel blocker. By using radicalar (NO) and nitroxyl (NO) scavenger, our results suggest that the BPY mainly release the radicalar species. By using fluorescence probes to detect intracellular NO concentration ([NO]i) and cytosolic Ca concentration ([Ca]c), we verified that in smooth muscle cells, BPY induces an increase in [NO]i and a decrease in [Ca]c. The intravenous bolus injection of 1.25, 2.5, and 5.0 mg/kg from stable configuration of BPY results in a decrease on basal blood pressure values. Taken together, our results indicated that the stable configuration of the compound BPY induces vascular relaxation in aorta because of NO release and decrease of [Ca]c in vascular smooth muscle cells. Also, the stable configuration is able to reduce the blood pressure in a dose-dependent manner. |
| Databáze: | OpenAIRE |
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