R.R. Campos

Vitamin C prevents DNA damage induced by renovascular hypertension in multiple organs of Wistar rats

The aim of this study was to investigate, through the single-cell gel (comet) assay, whether vitamin C is able to protect against renovascular hypertension-induced genotoxicity in multiple organs. A total of 32 male Wistar rats were divided into four groups: negative control (n = 6); animals treated with vitamin C (n = 6); hypertensive rats (n = 10) and hypertensive rats and treated with vitamin C (n = 10). Hypertension was induced as a result of partial obstruction of the left renal artery by means of a silver clip during 6 weeks. Vitamin C was administered at 150 mg/kg during 7 consecutive days before the end of the experimental period. The results showed that vitamin C was able to protect blood cells against hypertension-induced genotoxicity. Brain, liver and heart cells were also protected by vitamin C following hypertension-induced genotoxic damage. Regarding blood pressure, vitamin C reduced the hypertensive state. In conclusion, our results suggest that vitamin C can prevent hypertension-induced DNA damage in blood, liver, brain and heart cells as well as to normalize the blood pressure of rats.

Chronic renal failure induces genetic instability in multiple organs of Wistar rats

Background  Taking into consideration the strong evidence for a relationship between DNA damage and carcinogenesis, the aim of this study was to investigate whether blood, liver, heart, kidney and brain are particularly sensitive organs for DNA damaging during chronic renal disease by the single‐cell gel (comet) assay to predict genetic instability induced by this pathological condition.

Changes in GABAergic inputs in the paraventricular nucleus maintain sympathetic vasomotor tone in chronic heart failure

The paraventricular nucleus (PVN) of the hypothalamus is an important region of the brain involved in the regulation of sympathetic vasomotor tone. Accumulating evidence supports the idea that a change in hypothalamic γ-aminobutyric acid (GABA)-ergic inhibitory and glutamatergic excitatory inputs contribute to the exacerbated sympathetic drive in chronic heart failure (HF). The purpose of this study was to determine whether a possible imbalance between glutamatergic and GABAergic inputs to the PVN contributes to increased sympathetic outflow in HF in two different sympathetic territories. Renal (RSNA) and splanchnic sympathetic nerve activity (SSNA), mean arterial blood pressure (MAP) and heart rate were recorded from urethane-anesthetized HF or sham rats. The NMDA-glutamate and GABA-A receptor densities within the PVN were quantified in HF and sham rats by autoradiography. Bilateral microinjection of kynurenic acid (4nmol) into the PVN decreased MAP and RSNA and SSNA in HF but not in sham rats. Furthermore, in response to GABA-A blockade in the PVN by bicuculline (400 pmol), hypertension and SSNA were reduced in HF compared to sham. The quantification of ionotropic NMDA receptors and GABA-A receptors in the PVN showed a significant reduction of GABA-A in HF rats; however, the NMDA density in the PVN did not differ between groups. Thus, this study provides evidence that the sympathoexcitation is maintained by an imbalance between GABAergic and glutamatergic inputs in the PVN in HF. The reduced GABAergic input results in relatively augmented glutamatergic actions in the PVN of HF rats.

Reactive Oxygen Species within the Spinal Cord Impairs Arterial Baroreflex Control of Renal Sympathetic Nerve Activity

Clinical and experimental studies have shown that sustained increase in renal sympathetic nerve activity (rSNA) contributes to hypertension. Previous studies by our group showed that antioxidant treatments improve arterial baroreceptor reflex, which is a powerful beat-to-beat negative feedback control of arterial blood pressure (BP). We hypothesized that reactive oxygen species (ROS) contribute to arterial baroreflex control of rSNA by acting on sympathetic preganglionic neurons in the spinal cord. We then performed the intrathecal (i.t.) administration of tempol (4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-N-oxyl) (5nmol), a superoxide dismutase mimetic. We evaluated the cardiovascular effects, basal and reflex rSNA evoked by i.t. injection of tempol. No significant changes in basal levels of heart rate (HR), mean arterial pressure (MAP) and rSNA were found. However, tempol significantly increased renal reflex sympathoinhibitory responses (pre tempol: -0.61 ± 0.15; post tempol: -1.55 ± 0.14* spikes/s/mmHg). Thus, the results suggest that ROS exert a tonic inhibitory influence on the activity of spinal neurons with barosensitive properties, and it seems to be a preferential influence on fibers involved in reflex sympathoinhibitory responses. Our study raises the possibility that ROS in the spinal cord mediate part of the baroreflex dysfunction in cardiovascular diseases, such as hypertension and heart failure, which is detrimental to patient outcome.