The bed nucleus of the stria terminalis modulates exercise-evoked cardiovascular responses in rats

Dynamic exercise evokes sustained cardiovascular changes, which are characterized by blood pressure and heart rate (HR) increases. Although it is well accepted that there is a central nervous system (CNS) mediation of cardiovascular adjustments during dynamic exercise, information on the role of specific CNS structures is limited. The bed nucleus of the stria terminalis (BST) is a forebrain structure known to be involved in central cardiovascular control. Based on this, we tested the hypothesis that BST modulates HR and mean arterial pressure (MAP) responses evoked when rats are submitted to dynamic exercise. Male Wistar rats were tested at three levels of exercise (0.4, 0.8 and 1 km h⁻¹) on a rodent treadmill before and after BST treatment with CoCl₂, a non-selective neurotransmission blocker. Bilateral microinjection of CoCl₂ (1 nmol in 100 nl artificial cerebrospinal fluid) into the BST reduced the pressor response to exercise at 0.4 km h⁻¹ as well as the tachycardic responses evoked by exercise at 0.4, 0.8 and 1 km h⁻¹. The BST treatment with CoCl₂ did not affect baseline MAP or HR, suggesting a lack of tonic BST influence on cardiovascular parameters at rest. Moreover, BST treatment with CoCl₂ did not affect motor performance in the open-field test, which indicates that effects of BST inhibition on cardiovascular responses to dynamic exercise are not due to changes in motor activity. The present results suggest that local neurotransmission in the BST modulates exercise-related cardiovascular adjustments. Data indicate that BST facilitates pressor and tachycardic responses evoked by dynamic exercise in rats.     

Diuretic and potassium-sparing effect of isoquercitrin-an active flavonoid of Tropaeolum majus L

Aim of the study

Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic effects supporting the ethnopharmacological use of this plant as diuretic. In the present work, phytochemical investigation, guided by bio-assay in spontaneously hypertensive rats (SHR), was carried out in order to identify the compounds responsible for diuretic action.

Material and methods

Chromatographic fractionation of the hydroethanolic extract yielded an active fraction (TMLR) rich in isoquercitrin. TMLR (25-100 mg/kg) and isoquercitrin (5-10 mg/kg), as well the reference drug hydrochlorothiazide (10 mg/kg) were orally administered in a single dose or daily for 7 days to SHR. The urine excretion rate, pH, density, conductivity and content of sodium (Na⁺) and potassium (K⁺) electrolytes were measured in the urine of saline-loaded animals.

Results

The urinary excretion rate was dose-dependently increased in both TMLR and isoquercitrin groups, as well as Na⁺. Despite the changes in urinary excretion of electrolytes, the plasmatic levels of Na⁺ and K⁺ had not been changed. In addition, we did not find any evidence of renal toxicity or other adverse effects in these animals, even after prolonged treatment with TMLR or isoquercitrin.

Conclusion

This research supports and extends the ethnomedicinal use of T. majus as diuretic. This activity seems to be associated to the presence of the flavonol isoquercitrin.     

Bed nucleus of the stria terminalis N‐methyl‐D‐aspartate receptors and nitric oxide modulate the baroreflex cardiac component in unanesthetized rats

The bed nucleus of the stria terminalis (BST) plays a tonic role modulating the baroreflex bradycardiac response. In the present study, we verified whether local BST glutamatergic receptors and nitric oxide (NO) system modulate baroreflex bradycardiac responses. Bilateral BST‐ N‐methyl‐D‐aspartate (NMDA) receptor inhibition by treatment with the selective NMDA receptor antagonist LY235959 increased bradycardiac response to mean arterial pressure increases. Treatment with the selective non‐NMDA antagonist NBQX did not affect reflex bradycardia. These results suggest an involvement of local NMDA receptors in the BST‐related tonic inhibitory modulation of baroreflex bradycardiac response. BST treatment with the nonselective NO synthase (NOS) inhibitor L‐NAME or the selective neuronal NOS (nNOS) inhibitor N^ω‐propyl‐L‐arginine increased bradycardiac response, indicating that NO generated by nNOS activation modulates baroreflex. The NO involvement was further reinforced by observation that BST treatment with the NO scavenger carboxy‐PTIO caused an effect similar to that observed after NMDA receptor blockade or treatment with NOS inhibitors. Additionally, it was observed that LY235959 effects on baroreflex bradycardiac response were reverted by BST treatment with the NO‐donor sodium nitroprusside, suggesting an NMDA receptor–NO interaction. Baroreflex bradycardiac responses observed before and after BST treatment with LY235959 or N^ω‐propyl‐L‐arginine were no longer different when animals were pretreated intravenously with the anticholinergic drug homatropine methyl bromide. These results indicate that parasympathetic activation accounts for the effects observed after BST pharmacological manipulation. In conclusion, our data point out that local NMDA and nNOS interaction mediates the tonic inhibitory influence of the BST on the baroreflex bradycardiac response, modulating the parasympathetic cardiac activity. © 2009 Wiley‐Liss, Inc.