Pharmacological characterization of the vasodilating effect induced by the ruthenium complex cis-[Ru(NO)(NO2)(bpy)2].(PF6)2.
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.
*Department of Physiological Sciences, Federal University of São Carlos, Rodovia Washington Luís, São Paulo, Brazil; and †Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Gerson J
GJ
Rodrigues
Amanda C
AC
Pereira
Thiago F
TF
de Moraes
Charles C
CC
Wang
Roberto S
RS
da Silva
Lusiane M
LM
Bendhack
D000818:Animals; D001011:Aorta; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017975:Ruthenium Compounds / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D017975:Ruthenium Compounds; D014665:Vasodilator Agents; D009569:Nitric Oxide; D006162:Guanylate Cyclase