Role of the endothelial reverse mode sodium-calcium exchanger in the dilation of the rat middle cerebral artery during hypoosmotic hyponatremia.

A decrease in serum sodium ion concentration below 135 mmol L-1 is usually accompanied by a decrease in plasma osmolality (hypoosmotic hyponatremia) and leads to the disorder of intracranial homeostasis mainly due to cellular swelling. Recently, using an in vitro model of hypoosmotic hyponatremia, we have found that a decrease in sodium ion concentration in the perfusate to 121 mmol L-1 relaxes the isolated rat middle cerebral artery (MCA). The aim of the present study was to explore the mechanism responsible for this relaxation. Isolated, pressurized, and perfused MCAs placed in a vessel chamber were subjected to a decrease in sodium ion concentration to 121 mmol L-1. Changes in the diameter of the vessels were monitored with a video camera. The removal of the endothelium and inhibition of nitric oxide-dependent signaling or the reverse mode sodium-calcium exchanger (NCX) were used to study the mechanism of the dilation of the vessel during hyponatremia. The dilation of the MCA (19 ± 5%, p < 0.005) in a low-sodium buffer was absent after removal of the endothelium or administration of the inhibitor of the reverse mode of sodium-calcium exchange and was reversed to constriction after the inhibition of nitric oxide (NO)/cGMP signaling. The dilation of the middle cerebral artery of the rat in a 121 mmol L-1 Na+ buffer depends on NO signaling and reverse mode of sodium-calcium exchange. These results suggest that constriction of large cerebral arteries with impaired NO-dependent signaling may be observed in response to hypoosmotic hyponatremia.

Indole-3-propionic acid, a tryptophan-derived bacterial metabolite, increases blood pressure via cardiac and vascular mechanisms in rats.

Recent evidence suggests that gut bacteria-derived metabolites interact with the cardiovascular system and alter blood pressure (BP) in mammals. Here, we evaluated the effect of indole-3-propionic acid (IPA), a gut bacteria-derived metabolite of tryptophan, on the circulatory system. Arterial BP, electrocardiographic, and echocardiographic (ECHO) parameters were recorded in male, anesthetized, 12-wk-old Wistar-Kyoto rats at baseline and after intravenous administration of either IPA or vehicle. In additional experiments, rats were pretreated with prazosin or pentolinium to evaluate the involvement of the autonomic nervous system in cardiovascular responses to IPA. IPA's concentrations were measured using ultra-high performance liquid chromatography tandem mass spectrometry. The reactivity of endothelium-intact and -denuded mesenteric resistance arteries was tested. Cells' viability and lactate dehydrogenase (LDH) cytotoxicity assays were performed on cultured cardiomyocytes. IPA increased BP with a concomitant bradycardic response but no significant change in QTc interval. The pretreatment with prazosin and pentolinium reduced the hypertensive response. ECHO showed increased contractility of the heart after the administration of IPA. Ex vivo, IPA constricted predilated and endothelium-denuded mesenteric resistance arteries and increased metabolic activity of cardiomyocytes. IPA increases BP via cardiac and vascular mechanisms in rats. Furthermore, IPA increases cardiac contractility and metabolic activity of cardiomyocytes. Our study suggests that IPA may act as a mediator between gut microbiota and the circulatory system.

Compromised regulation of the rat brain parenchymal arterioles in vasopressin-associated acute hyponatremia.

OBJECTIVE: In this study, we examined the effect of acute hyponatremia associated with vasopressin (AVP) on the responses of the isolated rat's MCAs and PAs to acidosis, nitric oxide donor (SNAP) and to endothelium-dependent vasodilator ATP. METHODS: The studies were performed on isolated, perfused and pressurized MCAs and PAs in control conditions and during AVP-associated hyponatremia. Hyponatremia was induced in vitro by lowering Na+ concentration from 144 to 121 mmol/L in intra- and extravascular fluid in the presence of AVP. RESULTS: Parenchymal arterioles showed greater response to an increase in H+ and K+ ions concentration and to ATP in comparison with MCAs in control normonatremic conditions. Both PAs and MCAs constricted in response to acute hyponatremia associated with AVP. Interestingly, disordered regulation of vascular tone was observed in PAs but not in MCAs. The abnormalities in the regulation comprised a significant reduction of PA response to acidosis and the absence of the response to the administration of SNAP or ATP. CONCLUSIONS: Arginine vasopressin-associated hyponatremia leads to constriction and dysregulation of PAs which may impair neurovascular coupling.

Dysfunction of the endothelium and constriction of the isolated rat's middle cerebral artery in low sodium environment in the presence of vasopressin.

Hyponatraemia, a water-electrolyte disorder diagnosed in patients with subarachnoid haemorrhage (SAH), increases a risk of persistent vasospasm. In majority of cases, hyponatraemia results from inappropriate secretion of vasopressin (AVP). The effect of AVP-associated hyponatraemia on cerebral vasculature is unknown. The present study aimed to elucidate the role of AVP in the response of the middle cerebral artery (MCA) of the rat to hyponatraemia. Isolated, cannulated, and pressurized rat MCAs were perfused/superfused with physiological (Na+  = 144 mmol/L) buffer or low-sodium (Na+  = 121 mmol/L) buffer containing either AVP or angiotensin II (ANG II). ANG II was used to check if the effect of low plasma sodium concentration combined with AVP on the MCA tone is unique to vasopressin. At physiological Na+ concentration, vasopressin (1.4 × 10-11  mol/L) or angiotensin II (10-9  mol/L) resulted in relaxation of the MCA. Substitution of low-sodium for the normal sodium buffer with the same concentration of AVP, resulted in the constriction of the MCA. This effect was absent after removal of the endothelium, administration of vasopressin V1 receptor antagonist or concomitant inhibition of endothelin-1 receptors and synthesis of thromboxane A2. In contrast, no constriction of the MCA in low-sodium buffer was observed when AVP was replaced with ANG II. Our data suggest that presence of vasopressin and low sodium ion concentration results in the change of endothelium phenotype from pro-vasodilatory to pro-vasoconstrictory. This phenomenon may be an overlooked factor contributing to vasospasm in SAH patients with hyponatraemia caused by inappropriate antidiuretic hormone secretion (SIADH).

Butyric acid, a gut bacteria metabolite, lowers arterial blood pressure via colon-vagus nerve signaling and GPR41/43 receptors.

Butyric acid (BA) is a short-chain fatty acid (SCFA) produced by gut bacteria in the colon. We hypothesized that colon-derived BA may affect hemodynamics. Arterial blood pressure (BP) and heart rate (HR) were recorded in anesthetized, male, 14-week-old Wistar rats. A vehicle, BA, or 3-hydroxybutyrate, an antagonist of SCFA receptors GPR41/43 (ANT) were administered intravenously (IV) or into the colon (IC). Reactivity of mesenteric (MA) and gracilis muscle (GMA) arteries was tested ex vivo. The concentration of BA in stools, urine, portal, and systemic blood was measured with liquid chromatography coupled with mass spectrometry. BA administered IV decreased BP with no significant effect on HR. The ANT reduced, whereas L-NAME, a nitric oxide synthase inhibitor, did not affect the hypotensive effect of BA. In comparison to BA administered intravenously, BA administered into the colon produced a significantly longer decrease in BP and a decrease in HR, which was associated with a 2-3-fold increase in BA colon content. Subphrenic vagotomy and IC pretreatment with the ANT significantly reduced the hypotensive effect. Ex vivo, BA dilated MA and GMA. In conclusion, an increase in the concentration of BA in the colon produces a significant hypotensive effect which depends on the afferent colonic vagus nerve signaling and GPR41/43 receptors. BA seems to be one of mediators between gut microbiota and the circulatory system.

Effect of vasopressin-induced chronic hyponatremia on the regulation of the middle cerebral artery of the rat.

Vasopressin (arginine vasopressin, AVP) plays a crucial role in maintaining body fluid homeostasis. Excessive release of vasopressin can lead to hyponatremia. Changes in cerebral circulation during vasopressin-induced chronic hyponatremia are not elucidated. The present study has been designed to investigate the effect of chronic vasopressin-induced hyponatremia on the regulation of the tone of the middle cerebral artery (MCA) of the rat. Chronic hyponatremia was induced in vivo with the help of vasopressin, released continuously from subcutaneously implanted ALZET mini-osmotic pumps, and a liquid diet. After 3.5 days of chronic hyponatremia, the plasma Na+ concentration decreased to 119 ± 3 mM. MCAs were isolated and placed in a MOPS-buffered saline solution containing 121 mM Na+. Chronic hyponatremia did not affect the response of the MCA to increased intravascular pressure, to the administration of acetylcholine (ACh) and nitric oxide (NO) donor (SNAP, S-nitroso-N-acetyl-DL-penicillamine), and to increased K+ concentration, but impaired the response of the MCA to increased extravascular H+ concentration. Disturbed response of the MCA to acidosis was associated neither with the impairment of KATP channels nor with the activation of vasopressin V1 receptor. Correction of hyponatremia did not restore the response of the MCA to acidosis. These results indicate that cerebral blood vessels do not fully adapt to prolonged vasopressin-induced hyponatremia.

Cerebrovascular reactivity and cerebral perfusion of rats with acute liver failure: role of L-glutamine and asymmetric dimethylarginine in L-arginine-induced response.

Cerebral blood flow (CBF) is impaired in acute liver failure (ALF), however, the complexity of the underlying mechanisms has often led to inconclusive interpretations. Regulation of CBF depends at least partially on variations in the local brain L-arginine concentration and/or its metabolic rate. In ALF, other factors, like an increased concentration of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor and elevated level of L-glutamine, may contribute to CBF alteration. This study demonstrated strong differences in the reactivity of the middle cerebral arteries and their response to extravascular L-arginine application between vessels isolated from rats with thioacetamide (TAA)-induced ALF and control animals. Our results also showed the decrease in the cerebral perfusion in TAA rats measured by arterial spin labeling perfusion magnetic resonance. Subsequently, we aimed to investigate the importance of balance between the concentration of ADMA and L-arginine in the CBF regulation. In vivo, intraperitoneal L-arginine administration in TAA rats corrected: (i) decrease in cerebral perfusion, (ii) decrease in brain extracellular L-arginine/ADMA ratio and (iii) increase in brain L-glutamine concentration. Our study implicates that impaired vascular tone of cerebral arteries is most likely associated with exposure to high ADMA and L-glutamine levels resulting in limited availability of L-arginine and might be responsible for reduced cerebral perfusion observed in ALF.

Deoxycholic Acid, a Secondary Bile Acid, Increases Cardiac Output and Blood Pressure in Rats.

BACKGROUND: Deoxycholic acid (DCA) is a secondary bile acid produced by gut bacteria. Elevated serum concentrations of DCA are observed in cardiovascular disease (CVD). We hypothesized that DCA might influence hemodynamic parameters in rats. METHODS: The concentration of DCA in systemic blood was measured with liquid chromatography coupled with mass spectrometry. Arterial blood pressure (BP), heart rate (HR) and echocardiographic parameters were evaluated in anesthetized, male, 3-4-month-old Sprague-Dawley rats administered intravenously (IV) or intracerebroventricularly (ICV) with investigated compounds. Mesenteric artery (MA) reactivity was tested ex vivo. RESULTS: The baseline plasma concentration of DCA was 0.24 ± 0.03 mg/L. The oral antibiotic treatment produced a large decrease in the concentration. Administered IV, the compound increased BP and HR in a dose-dependent manner. DCA also increased heart contractility and cardiac output. None of the tested compounds-prazosin (an alpha-blocker), propranolol (beta-adrenolytic), atropine (muscarinic receptor antagonist), glibenclamide (K-ATP inhibitor) or DY 268 (FXR antagonist), glycyrrhetinic acid (11HSD2 inhibitor)-significantly diminished the DCA-induced pressor effect. ICV infusion did not exert significant HR or BP changes. DCA relaxed MAs. Systemic vascular resistance did not change significantly. CONCLUSIONS: DCA elevates BP primarily by augmenting cardiac output. As a metabolite derived from gut bacteria, DCA potentially serves as a mediator in the interaction between the gut microbiota and the host's circulatory system.

Hyponatremia as a risk factor for microvascular spasm following subarachnoid hemorrhage.

Hyponatremia is a water-electrolyte balance disorder diagnosed in about 30% of patients after subarachnoid hemorrhage (SAH). The main factors responsible for hyponatremia in these patients are increased plasma concentrations of either vasopressin (leading to water retention and dilutional hyponatremia) or natriuretic peptides (leading to plasma sodium ions deficiency). Data demonstrates that the leading causes of post-SAH disability - delayed cerebrovascular spasm (CVS) and delayed cerebral ischemia (DCI) - are more often diagnosed in patients who develop hyponatremia than in normonatremic patients with SAH. Data also indicates that reducing sodium ion concentration in the blood/perfusate affects the tone and regulation of cerebral blood vessels in a manner that depends on the vessel's location in a vascular tree (intraparenchymal arterioles vs. large vessels on the brain surface) and environmental conditions. In the present article, we review possible mechanisms underlying the effects of hyponatremia on cerebral blood vessels and discuss the potential role of hyponatremia in the development of large vessels and microvascular spasm, taking into consideration the presence of vasopressin and natriuretic peptides.

Treatment of severe refractory dystonic tremor associated with cervical dystonia by bilateral deep brain stimulation: A case series report.

OBJECTIVES: The aim of the present study was to present a case series of 3 patients with longstanding, severe, debilitating dystonic head tremor (DT) coexistence with cervical dystonia (CD) treated successfully by bilateral deep brain stimulation (DBS). Pharmacological treatment including benzodiazepines and botulinum toxin injections employed to overactive muscles have failed to adequately control dystonic jerking movements of the head and neck. PATIENTS AND METHODS: All patients were diagnosed with DT who accompanied CD. Two patients underwent bilateral implantation of DBS leads into the posteroventrolateral segment of the globus pallidus internus (GPi). 1 patient received combination of implantation of left lead in the nucleus ventralis intermedius of the thalamus (Vim) and the bilateral implantation of DBS leads in the GPi. All surgeries were uneventful. The formal preoperative objective assessment included Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the motor score of Tremor Rating Scale (TRS). The postoperative TWSTRS, TRS assessments were done at 3, 6 months and 12 months postoperatively up to 48 months after surgery. RESULTS: At the 12 months postoperative follow-up visit, the severity, disability and pain scores of TWSTRS were improved by 56 %, 52 % and 38,5 % respectively. The TRS improved by 66 % at 12 months when compared to baseline TRS score. One patient developed seroma over the implanted internal pulse generator and had some wound healing problems which solved without sequel. There were no hardware-related complications over follow-up period. CONCLUSION: Our experience gathered in 3 patients indicates that bilateral DBS can be an effective treatment for disabling, pharmacological refractory tremulous CD.

Valeric acid lowers arterial blood pressure in rats.

Valeric acid (VA) is a short-chain fatty acid produced by microbiota and herbs such as Valeriana officinalis. Moreover, VA is released from medicines such as estradiol valerate by esterases. We evaluated the concentrations of endogenous VA in male, 14-week-old rats in the liver, heart, brain, kidneys, lungs, blood and in the colon, a major site of microbiota metabolism, using liquid chromatography coupled with mass spectrometry. In addition, the tissue distribution of VA D9-isotope (VA-D9) administered into the colon was assessed. Finally, we investigated the effect of exogenous VA on arterial blood pressure (BP) and heart rate (HR) in anesthetized rats, and the reactivity of mesenteric (MA) and gracilis muscle (GMA) arteries ex vivo. Physiological concentration of VA in the colon content was ≈650 µM, ≈ 0.1-1 µM in the investigated tissues, and ≈0.4 µM in systemic blood. VA-D9 was detected in the tissues 5 min after the administration into the colon. The vehicle did not affect BP and HR. VA produced a dose-dependent decrease in BP, and at higher doses lowered HR. The hypotensive effect of VA was inhibited by 3-hydroxybutyrate, an antagonist of GPR41/43-receptors but not by the subphrenic vagotomy. Hexamethonium prolonged the hypotensive effect of VA while atropine did not influence the hypotensive effect. VA dilated GMA and MA. In conclusion, the exogenous VA produces vasodilation and lowers BP. The colon-derived VA rapidly penetrates to tissues involved in the control of BP. Further studies are needed to evaluate the effects of endogenous and exogenous VA on the circulatory system.

Large Hemorrhagic Cerebral Venous Infarction due to Deep Brain Stimulation Leads Placement. Report of 2 Cases.

The true incidence of hemorrhagic venous infarctions in deep brain stimulation (DBS) procedures is very difficult to determine. These hemorrhagic venous complications are very rare and often grouped as all hemorrhagic complications. We report the clinical cases of 2 patients with Parkinson's disease (PD) who received unilateral globus pallidus DBS and developed hemorrhagic venous infarctions. In these 2 patients a small injury to a dural outflow venous structure or a superficial brain vein resulted in hemorrhagic venous infarctions. We present the management of these rare complication with detailed radiologic follow-up. The first patient made a full recovery but the second patient deceased 5 months after DBS surgery due to aspiration pneumonia. We stress that careful planning of a stereotactic trajectory reduces significantly hemorrhagic complications in DBS surgery but not fully exclude some side effects like venous hemorrhagic infarctions which may result in prolong hospitalization or death.

Hemorrhagic complications seen on immediate intraprocedural stereotactic computed tomography imaging during deep brain stimulation implantation.

BACKGROUND: We present our operative experience of patients with movement disorders who developed intracerebral hemorrhage (ICH), which was identified on intraprocedural stereotactic computed tomography (CT) imaging performed immediately after deep brain stimulation (DBS) lead placement and prior to the implantation of further components of the DBS hardware. METHODS: Patients who underwent DBS lead implantation from January 2009 through December 2017 were included in the present study. Most of the surgeries were performed in a staged fashion. All patients were operated using identical surgical and intraprocedural imaging techniques, and no microelectrode recordings were done. Leksell Stereotactic G frame and neuronavigation software was utilized for all surgeries. Intraprocedural stereotactic CT was performed to confirm the precise position of the implanted DBS lead and to rule out any hemorrhagic complications. RESULTS: Overall, 222 patients underwent 322 DBS lead implantations during 316 stereotactic procedures. Six patients exhibited early ICH recognized on intraprocedural stereotactic CT performed immediately after DBS lead placement; in addition, two patients developed delayed ICH due to large venous infarction. Four patients with ICH were asymptomatic. The ICH rate was 2.5% per electrode and 3.6% per patient; the permanent deficit rate was 1.2% per electrode and 1.8% per patient. The death rate due to ICH in our cohort was 0.6% per electrode and 0.9% per patient. CONCLUSIONS: Intraprocedural stereotactic CT can not only visualize the implanted DBS lead in the stereotactic space but also rule out early ICH. Identified predisposing factors for development of ICH include patient's age, hypertension, and previous antiplatelet therapy. Careful planning of stereotactic trajectories plays a paramount role in reducing the rate of ICH in DBS surgery.

The Influence of Unilateral Subthalamic Deep Brain Stimulation on the Quality of Life of Patients with Parkinson's Disease.

AIM: To assess the health-related quality of life (HRQoL) with the Parkinson"s Disease Questionnaire 39 (PDQ-39) after unilateral subthalamic deep brain stimulation (STN DBS) and to identify correlations between the changes in UPDRS (Unified Parkinson"s Disease Rating Scale) scores and separate PDQ-39 QoL dimensions and PDQ summary index (SI) score at short-term follow-up (FU1) and long-term follow-up (FU2). MATERIAL AND METHODS: We evaluated 33 patients with PD after unilateral STN DBS. All patients were assessed at baseline and at FU1 and at FU2. HRQoL levels were determined by applying PDQ-39 and PD progression was evaluated by parts I-IV of the UPDRS. RESULTS: All dimensions of PDQ-39 as well as PDQ-39 SI score were highly significantly improved at FU1. The same improvements were mostly visible at FU2 except for psychosocial functioning. The PDQ-39 SI score was reduced by 40 % (p < 0.01) at FU1 and by 25 % (p < 0.01) at FU2. A significant reduction between the UPDRS baseline scores and the UPDRS follow-up scores was noticed for medication off and on conditions under unilateral STN DBS. Interestingly, we did not find strong positive correlations between the improvements of the UPDRS scores and individual PDQ-39 dimensions as well as PDQ-39 SI score. CONCLUSION: Improvements in PDQ-39 dimensions and PDQ-39 SI score are maintained at FU1 and except for the aspects of psychosocial functioning at FU2. Different correlations between the improvements of separate UPDRS scores on PDQ-39 dimensions require future studies in larger study groups.

Restoration of the response of the middle cerebral artery of the rat to acidosis in hyposmotic hyponatremia by the opener of large-conductance calcium sensitive potassium channels (BKCa).

Hyposmotic hyponatremia (the decrease of extracellular concentration of sodium ions from 145 to 121 mM and the decrease of hyposmolality from 300 to 250 mOsm/kg H2O) impairs response of the middle cerebral artery (MCA) to acetylcholine and NO donor (S-nitroso-N-acetyl-DL-penicillamine). Since acidosis activates a similar intracellular signaling pathway, the present study was designed to verify the hypothesis that the response of the MCA to acidosis is impaired during acute hyposmotic hyponatremia due to abnormal NO-related signal transduction in vascular smooth muscle cells. Studies performed on isolated, cannulated, and pressurized rat MCA revealed that hyposmotic hyponatremia impaired the response of the MCA to acidosis and this was associated with hyposmolality rather than with decreased sodium ion concentration. Response to acidosis was restored by the BKCa but not by the KATP channel activator. Patch-clamp electrophysiology performed on myocytes freshly isolated from MCAs, demonstrated that hyposmotic hyponatremia does not affect BKCa currents but decreases the voltage-dependency of the activation of the BKCa channels in the presence of a specific opener of these channels. Our study suggests that reduced sensitivity of BKCa channels in the MCA to agonists results in the lack of response of this artery to acidosis during acute hyposmotic hyponatremia.

Long-term clinical outcome of bilateral pallidal stimulation for intractable craniocervical dystonia (Meige syndrome). Report of 6 patients.

BACKGROUND: The aim of the present study was to report the short-term as well long-term results of bilateral pallidal stimulation in 6 consecutive patients for severe debilitating craniocervical dystonia (Meige syndrome) using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). METHODS: We evaluated 6 consecutive patients with the diagnosis of intractable long-standing craniocervical dystonia. The formal objective assessment included the motor and disability BFMDRS scores. The BFMDRS assessment was performed before and after it roughly annually up to 60months when bilateral pallidal stimulation was switched on and compared to baseline BFMDRS scores. We present short-term (3months postoperatively) follow-up as well long-term (from 6 to 60months) results. Baseline BFMDRS scores and subsequent follow-up BFMDRS scores were compared with the use of a Wilcoxon signed-rank test for matched pairs. A two-tailed probability level of 5% (p<0.05) was considered significant. RESULTS: Bilateral GPi DBS improved the BFMDRS total movement score by 65% at short-term follow-up and by 53% at long-term follow-up when compared to baseline scores. Subscores for eyes at short-term follow-up were reduced by 78%, for mouth by 58%, and for speech/swallowing by 49%. This improvements for individual subscores were maintained at long-term follow-up and were as follows for eyes by 67%, mouth by 50% and speech/swallowing by 39%. The BFMDRS disability score was reduced by 48% at short-term follow-up and by 55% at long-term follow-up when compared to baseline scores. CONCLUSION: Our results showed that bilateral GPi DBS in craniocervical dystonia is effective and safe. Phasic dystonic movements like blepharospasm or oromandibular dystonia responded very fast and favorable to pallidal stimulation reducing disabilities.

The effect of simvastatin and pravastatin on arterial blood pressure, baroreflex, vasoconstrictor, and hypertensive effects of angiotensin II in Sprague-Dawley rats.

Research suggests that statins affect the regulation of arterial blood pressure (BP), however, the mechanisms remain obscure. We maintained male, 12-week-old, Sprague-Dawley rats on tap water (controls) or water containing simvastatin or pravastatin for 4 weeks. Subsequently, we measured mean arterial blood pressure and heart rate at baseline and after intravenous infusion of either saline or angiotensin II (Ang II). Additionally, we tested baroreflex function and the effect of statins on vasoconstrictor response to Ang II on isolated femoral artery branches. Controls and simvastatin and pravastatin groups showed a significant increase in mean arterial BP and heart rate in response to Ang II. The increase was significantly smaller in the simvastatin group than in controls and in the pravastatin group. In contrast, when pretreated with hexamethonium, a ganglionic blocker, simvastatin and pravastatin groups showed a similar hypertensive response to Ang II, which was smaller than in controls. Likewise, the Ang II-induced vasoconstrictor response of femoral artery branches was comparable between simvastatin and pravastatin groups and smaller than in controls. We found no effect of statins on the baroreflex. This study shows that simvastatin and pravastatin differ in their effects on the Ang II-dependent mechanisms controlling BP.

Disturbed regulation of the isolated middle cerebral artery in acute hyponatremia.

Hyponatremia is a common disorder of water-electrolyte balance characterized by the decrease of plasma sodium ions concentration below 135 mM. Although water-electrolyte balance is regulated by a kidney, symptoms of hyponatremia are related to the disturbances of intracranial homeostasis and are attributed to brain swelling. Despite the importance of blood vessels function for the homeostasis of the brain, little is known about the influence of hyponatremia on cerebrovascular regulation. In the present study isolated, perfused and pressurized rat middle cerebral arteries (MCAs) were subjected to hyponatremia in the organ chamber by lowering the concentration of sodium ions from 145 to 121 mM. The response of the MCAs to the changes in intravascular pressure and to endothelium-dependent and independent vasodilators was compared in normo- and hyponatremia. The following results were obtained: the contraction of the MCA during progressive increases in intravascular pressure was similar in normo- and hyponatremia; the dilation in response to acetylcholine (10-6 M, 10-5 M and 10-4 M), which is endothelium- and nitric oxide-dependent, was severely impaired in hyponatremia; the contraction after administration of the nonselective inhibitor of nitric oxide synthesis - NG-nitro-L-arginine methyl ester (L-NAME, 10-5 M) was similar in normo- and hyponatremia; the nitric oxide donor - S-nitroso-N-acetylpenicillamine (SNAP, 10-5 M) dilated MCA only in normonatremia. The results of this study show that myogenic response and shear stress-dependent relaxation of the MCA are not affected by acute hyponatremia. However, agonist-stimulated, endothelial nitric oxide synthase (eNOS)-mediated relaxation is severely impaired which is associated with a decreased smooth muscle response to nitric oxide (NO). In conclusion, our results demonstrate that the regulation of isolated middle cerebral artery is impaired in acute hyponatremia which may contribute to the disturbance of intracranial homeostasis associated with hyponatremia.