Cardiovascular diseases include all types of disorders related to the heart or blood vessels. High blood pressure is an important risk factor for cardiac complications and pathological disorders. An increase in circulating angiotensin-II is a potent stimulus for the expression of reactive oxygen species and pro-inflammatory cytokines that activate oxidative stress, perpetuating a deleterious effect in hypertension. Studies demonstrate the capacity of NO to prevent platelet or leukocyte activation and adhesion and inhibition of proliferation, as well as to modulate inflammatory or anti-inflammatory reactions and migration of vascular smooth muscle cells. However, in conditions of low availability of NO, such as during hypertension, these processes are impaired. Currently, there is great interest in the development of compounds capable of releasing NO in a modulated and stable way. Accordingly, compounds containing metal ions coupled to NO are being investigated and are widely recognized as having great relevance in the treatment of different diseases. Therefore, the exogenous administration of NO is an attractive and pharmacological alternative in the study and treatment of hypertension. The present review summarizes the role of nitric oxide in hypertension, focusing on the role of new NO donors, particularly the metal-based drugs and their protagonist activity in vascular function.

A maternal diet high in saturated fat during critical periods of development is associated with an increased risk of chronic diseases in adulthood. We investigated whether cardiovascular effects in adulthood can be altered by the maternal high-fat diet with flaxseed oil (omega-3) as well as the effects of this diet in dams. Wistar rats were fed during pregnancy and lactation according to the following: control (CT) – standard diet; high-fat (HL) – diet rich in saturated fatty acids; and high-fat with omega-3 (HLꞶ3) – diet rich in omega-3 from flaxseed oil. Body mass, lipid peroxidation, biochemical profile, heart and kidney weights and cardiac hypertrophy index (CHI) were measured in dams. In the offspring, body mass, murine parameters, dietary and water control, systolic and diastolic blood pressure at 60 and 90 days, biochemical parameters, heart and kidney weights, CHI and vascular reactivity were evaluated. In dams, the HLꞶ3 diet delayed the increase in body mass in lactation and reversed oxidative damage in the heart. Therefore, our data suggest that HL diet promotes adverse cardiometabolic effects and the HLꞶ3 diet attenuated the weight gain and oxidative stress in dams, while in the offspring the HLꞶ3 prevented the increase in the Phe-induced contraction.

Chronic kidney disease (CKD) is a progressive disorder characterized by declining renal function and increased cardiovascular risk. Experimental models are essential for investigating these mechanisms, and the 5/6 nephrectomy (5/6 Nx) model is widely used to reproduce cardiorenal alterations observed in CKD. This review aims to critically evaluate how effectively the 5/6 Nx model reproduces vasoactive and redox mechanisms relevant for pharmacological testing. A narrative synthesis of experimental studies using the 5/6 Nx model in rodents was performed, focusing on vascular, inflammatory, and oxidative pathways. The 5/6 Nx model reproduces major CKD features, including hypertension, proteinuria, glomerulosclerosis, and cardiovascular remodeling. Early activation of the renin–angiotensin–aldosterone system, endothelin signaling, and sympathetic pathways contributes to vascular dysfunction. Sustained oxidative stress reduces nitric oxide bioavailability and promotes endothelial dysfunction. Dysregulation of natriuretic peptides and increased 20-HETE signaling further contribute to vascular imbalance and remodeling. These alterations occur in a well-defined temporal progression, supporting the use of this model for mechanistic and pharmacological studies. The 5/6 Nx model remains a robust and translationally informative platform for investigating CKD progression, provided that pathway-specific reproducibility and experimental variables are carefully considered.

Background: Nitric oxide (NO) is a gaseous molecule considered to be a protagonist in the dilation of blood vessels, and its property and/or bioavailability are reduced in pathophysiological conditions such as cardiovascular diseases. Therefore, its exogenous administration becomes attractive, and new classes of compounds able to induce NO release have emerged to minimize the adverse effects found by existing NO donor drugs. Objective: Our aim was to investigate the vasorelaxant effect and mechanism of action induced by the ruthenium complex, which contains nitric oxide in its structure, [Ru(phen)₂(TU)NO](PF₆)₃ (FOR 911B), in isolated rat aorta. Methods: The animals were euthanized, and the aorta artery was identified, removed, and immediately placed in modified Krebs–Henseleit solution. To verify tissue viability, a contraction was obtained with phenylephrine (Phe) (0.1 μM), and to assess endothelial integrity, acetylcholine (ACh) (1 μM) was added. Results: In the present study, we demonstrated, for the first time, that FOR 911B promotes vasorelaxation in a concentration-dependent manner in isolated rat aortic artery rings. After the removal of the vascular endothelium, the potency and efficacy of the relaxation were not altered. With pre-incubation with hydroxocobalamin, the relaxing response was abolished, and with the use of ODQ, the main NO receptor blocker, the vasorelaxant effect was attenuated with a shift of the curve to the right. To investigate the participation of K⁺ channels, the solution concentration was changed to KCl (20 and 60 mM), and it was pre-incubated with the non-selective K⁺ channels blocker (TEA). Under these conditions, relaxation was altered, demonstrating that K⁺ channels are activated by FOR 911B. By selectively blocking the different subtypes of K⁺ channels with specific blockers, we demonstrated that the subtypes K_V, K_IR, SK_Ca, and BK_Ca are involved in the vasodilator effect induced by FOR 911B. Conclusions: The results obtained demonstrated that FOR 911B promotes vascular relaxation in aortic artery rings in a concentration-dependent manner and independent of the vascular endothelium through the participation of the NO/sGC/cGMP pathway, as well as with the involvement of different K⁺ channels.