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Nitrosyl ruthenium complexes are promising platforms for nitric oxide (NO) and nitroxyl (HNO) release, which exert their therapeutic application. In this context, we developed two polypyridinic compounds with the general formula cis-[Ru(NO)(bpy)2(L)]n+, where L is an imidazole derivative. These species were characterized by spectroscopic and electrochemical techniques, including XANES/EXAFS experiments, and further supported by DFT calculations. Interestingly, assays using selective probes evidenced that both complexes can release HNO on reaction with thiols. This finding was biologically validated by HIF-1α detection. The latter protein is related to angiogenesis and inflammation processes under hypoxic conditions, which is selectively destabilized by nitroxyl. These metal complexes also presented vasodilating properties using isolated rat aorta rings and demonstrated antioxidant properties in free radical scavenging experiments. Based on these results, the new nitrosyl ruthenium compounds showed promising characteristics as potential therapeutic agents for the treatment of cardiovascular conditions such as atherosclerosis, deserving further investigation. [ABSTRACT FROM AUTHOR]

This study investigated the cardiovascular responses to the essential oil of Aniba canelilla (EOAC) and its main constituent 1-nitro-2-phenylethane (NP) in spontaneously hypertensive rats (SHRs). In anesthetized SHRs, intravenous (i.v.) bolus injections of EOAC (1-20 mg/kg) or NP (1-10 mg/kg) elicited dose-dependent hypotensive and bradycardiac effects, which were characterized in two periods (phases 1 and 2). The first rapid component (phase 1) evoked by EOAC and NP both at 10 mg/kg was absent after left ventricle injection, fully abolished by bilateral vagotomy and perineural treatment of both cervical vagus nerves with capsaicin (250 μg/mL) while remained unaltered by i.v. pretreatment with capsazepine (1 mg/kg) or ondansetron (30 μg/kg). In conscious SHRs, NP (5 and 10 mg/kg, i.v.) evoked rapid hypotensive and bradycardiac effects (phase 1) that were fully abolished by methylatropine (1 mg/kg, i.v.) pretreatment. In rat endothelium-containing mesenteric preparations, increasing concentrations (0.1-1000 μg/mL) of EOAC and NP relaxed the phenylephrine-induced contraction in a concentration-dependent manner. It is concluded that NP induces a vago-vagal bradycardiac and depressor reflex (phase 1) that apparently results from the stimulation of vagal pulmonary rather than cardiac C-fiber afferents. This effect does not appear to involve activation of either vanilloid TPRV1 or 5-HT3 receptors located on vagal sensory nerves. The phase 2 hypotensive response to i.v. NP seems to result, at least in part, from its direct vasodilatory effect on the peripheral smooth muscle. All in vivo and in vitro effects of EOAC are mostly attributed to the actions of its main constituent NP. [ABSTRACT FROM AUTHOR]

The synthetic nitro-alcohol 2-nitro-1-phenyl-1-propanol (NPP) has endothelium-independent relaxing properties in isolated preparations of rat aorta and mesenteric artery. In this study, we investigated whether the vasodilator effects occur in coronary vessels and explored whether hyperpolarization is involved in the underlying mechanism of NPP-induced smooth muscle relaxation. The relaxing responses were studied in isolated preparations of the left anterior descending coronary (ADC) and the septal coronary (SC) arteries, which had been previously maintained under sustained contraction induced by the thromboxane A 2 analogue U-46619. Administered cumulatively, NPP elicited concentration-dependent vasorelaxation with similar potency in both vessels. The relaxant effect remained unaffected by the nitric oxide synthase inhibitor L-NAME, the protein kinase C inhibitor bisindolylmaleimide IV and the Rho-associated protein kinase inhibitor Y-27632. However, it was significantly diminished by the adenylyl cyclase inhibitor MDL-12,330A, the guanylyl cyclase inhibitor ODQ, as well as the K + channel inhibitors tetraethylammonium and CsCl. In ADC preparations impaled with intracellular micropipettes, NPP hyperpolarized the vascular preparation. When the isolated preparation was precontracted by 5-hydroxytryptamine or 80 mM KCl, NPP-induced relaxation with lower pharmacological potency compared to the vessels contracted by U-46619. In conclusion, NPP exhibits vasorelaxant effects on rat coronary arteries, likely involving pathways that include cyclic nucleotide production and membrane hyperpolarization., (© 2024 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)

Nitrosyl ruthenium complexes are promising platforms for nitric oxide (NO) and nitroxyl (HNO) release, which exert their therapeutic application. In this context, we developed two polypyridinic compounds with the general formula cis -[Ru(NO)(bpy) 2 (L)] n + , where L is an imidazole derivative. These species were characterized by spectroscopic and electrochemical techniques, including XANES/EXAFS experiments, and further supported by DFT calculations. Interestingly, assays using selective probes evidenced that both complexes can release HNO on reaction with thiols. This finding was biologically validated by HIF-1α detection. The latter protein is related to angiogenesis and inflammation processes under hypoxic conditions, which is selectively destabilized by nitroxyl. These metal complexes also presented vasodilating properties using isolated rat aorta rings and demonstrated antioxidant properties in free radical scavenging experiments. Based on these results, the new nitrosyl ruthenium compounds showed promising characteristics as potential therapeutic agents for the treatment of cardiovascular conditions such as atherosclerosis, deserving further investigation.

This study investigated the cardiovascular effects of the essential oil of Croton zehntneri (EOCZ) in deoxycorticosterone-acetate (DOCA)-salt hypertensive rats. Furthermore, in vitro experiments using isolated thoracic aortic rings were performed to assess the vascular effects of the EOCZ. In conscious hypertensive rats, intravenous (i.v.) injections of EOCZ (1-20 mg/kg) induced rapid (2-4 s) and dose-dependent hypotension and bradycardia (phase 1). The hypotension was followed by a significant pressor effect that was more evident at the higher doses (10 and 20 mg/kg) of EOCZ. Hypotension and bradycardia of EOCZ (phase 1) were abolished and respectively reversed into pressor and tachycardiac effects by methylatropine (1 mg/kg, i.v.) pretreatment. In isolated endothelium-intact aortic preparations, increasing concentrations (1-1000 microg/mL) of EOCZ relaxed the potassium-induced contraction in a concentration-dependent manner with an IC50 (geometric mean [95% confidence interval]) value of 202.0 [92.0-443.7] microg/mL. This vasorelaxant effect remained unaffected by either mechanical removal of functional vascular endothelium (IC50 = 189.0 [159.4-224.7] microg/mL) or the addition of atropine (1 microM) (IC50 = 158.6 [79.8-316.2] microg/mL) in the perfusion medium. These data show that i.v. administration of EOCZ in DOCA-salt hypertensive rats induces a vago-vagal reflex decreases in heart rate and blood pressure (phase 1). EOCZ may induce a second and delayed hypotension due to its direct endothelium-independent vasorelaxant effects, but it seems to be buffered by the pressor component (subsequent to phase 1) of EOCZ. This pattern of blood pressure and heart rate responses to EOCZ seems unaltered by DOCA-salt hypertension, as was similar to that previously reported in conscious normotensive rats.