Cardiovascular studies have confirmed that hydrogen sulphide (H2S) is involved in various signaling pathways in both physiological and pathological conditions, including hypertension. In contrast to nitric oxide (NO), which has a clear vasorelaxant action, H2S has both vasorelaxing and vasoconstricting effects on the cardiovascular system. H2S is an important antihypertensive agent, and the reduced production of H2S and the
alterations in its functions are involved in the initiation of spontaneous
hypertension. Moreover, cross-talk between H2S and NO has been reported. NO-H2S interactions include reactions between the molecules themselves, and each has been shown to regulate the endogenous production of the other. In addition, NO and H2S can interact to form a nitrosothiol/s complex, which has original properties and represents a novel nitroso-sulphide signaling pathway. Furthermore, recent results have shown that the interaction between H2S and NO could be involved in the endothelium-regulated compensatory mechanisms that are observed in juvenile spontaneously hypertensive rats. The present review is devoted to role of H2S in vascular tone regulation. We primarily focus on the mechanisms of H2S-NO interactions and on the role of H2S in blood pressure regulation in normotensive and spontaneously hypertensive rats.
The peroxisome proliferator-activated receptors (PPAR) belong to the nuclear superfamily of ligand-activated transcription factors. PPARγ acts as a nutrient sensor that regulates several homeostatic functions. Its disruption can lead to vascular pathologies, disorders of fatty acid/lipid metabolism and insulin resistance. PPARγ can modulate several signaling pathways connected with blood pressure regulation. Firstly, it affects the insulin signaling pathway and endothelial dysfunction by modulation of expression and/or phosphorylation of signaling molecules through the PI3K/Akt/eNOS or MAPK/ET-1 pathways. Secondly, it can modulate gene expression of the renin- angiotensin system – cascade proteins, which potentially slow down the progression of atherosclerosis and hypertension.
Thirdly, it can modulate oxidative stress response either directly through PPAR or indirectly through Nrf2 activation. In this context, activation and functioning of PPARγ is very important in the regulation of several disorders such as diabetes mellitus, hypertens
ion and/or metabolic syndrome.
Red wine polyphenols have been reported to possess beneficial properties for preventing cardiovascular diseases but their neuroprotective effects during chronic L-NAME treatment have not been elucidated. The aim of this study was to analyze a time course of Provinols
TM effects on brain NO synthase activity and oxidative damage in L-NAME-induced hypertension. Male Wistar rats, 12 weeks old, were divided into six groups: control groups, groups treated with N G-nitro-L-arginine methyl ester (L-NAME, 40 mg/kg/day) for 4 or 7 weeks and groups receiving ProvinolsTM (40 mg/kg/day) plus L-NAME for 4 or 7 weeks. At the end of the treatment, marker of membrane oxidative damage – conjugated dienes (CD) in the brain and NO synthase activity in the cerebral cortex, cerebellum and brainstem were determined. L-NAME treatment for 4 or 7 weeks led to the increase in blood pressure, elevation of CD concentration and decrease of NO synthase activity in the brain parts investigated. ProvinolsTM partially prevented blood pressure rise and elevation of CD concentration. Comparing to the L-NAME treated group, ProvinolsTM increased NO synthase activity after 4 weeks of treatment. However, the prolonged ProvinolsTM treatment for 7 weeks had no effect on NO synthase activity decreased by L-NAME treatment. In conclusion, ProvinolsTM partially prevents L-NAME induced hypertension via
the different mechanisms depending on the duration of treatment. Prevention of oxidative damage in the brain with modulating effect on NO synthase activity is suggested.