Central nifedipine-induced alterations in salivary flow and compounds: Role of nitric oxide

The aim of this study was to examine the role of nifedipine and Nitric Oxide (NO) on salivary flow and compounds (salivary amylase, saliva total proteins, saliva calcium, sodium and potassium). Male Holtzman rats weighting 200-250 g were anesthetized with zoletil 50 mg kg -1 (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle and stainless steel cannulas were implanted into their lateral ventricle of the brain (LV). Animals in divided group were injected with nifedipine (50 μg μL -1) alone and in combination with 7-nitroindazol (7-NIT) (40 μg μL -1), neuronal NO Sinthase Inhibitor (nNOSI) and Sodium Nitroprussate (SNP) (30 μg μL -1) NO donor agent. As a secretory stimuli, pilocarpine dissolved in isotonic was administered intraperitoneally (ip) at a dosage of 10 mg kg -1 body weight. Saliva was collected for 7 min with four cotton balls weighing approximately 20 mg each, two of which were placed on either side of the oral cavity, with the other two placed under the tongue. Nifedipine treatment induced a reduction in saliva secretion rate and concentration of amylase, total protein and calcium without changes in sodium and potassium concentration in comparison with controls. Co-treatment of animals with nifedipine and SNP retained flow rate and concentration of amylase, total protein and calcium in normal levels. Co-treatment of animals with nifedipine and 7-NIT potentiated the effect of nifedipine on the reduction of saliva secretion and concentrations of amylase, total protein and calcium. Nifedipine (dihydroperidine) calcium-channel blocker widely in use is associated with salivary dysfunction acting in the central nervous system structures. NO might be the mechanism for protective effect against the nifedipine-induce salivary dysfunction, acting in the CNS. © 2006 Asian Network for Scientific Information.

Nitrergic pathways and L-type calcium channel of MnPO influencing cardiovascular homeostasis

The median preoptic nucleus (MnPO) is one of most important site of the lamina terminalis implicated in the regulation of hydro electrolytic and cardiovascular balance. The purpose of this study was to determine the effect of L-Type calcium channel antagonist, nifedipine, on the increase of median arterial blood pressure (MAP) induce by angiotensin II (ANG II) injected into the MnPO. The influence of nitric oxide (NO) on nifedipine antipressor action has also been studied by utilizing N W-nitro-L-arginine methyl ester (L-NAME) (40 μg 0.2 μL -1) a NO synthase inhibitor (NOSI), 7-nitroindazole (7-NIT) (40 μg 0.2 μL -1), a specific neuronal NO synthase inhibitor (nNOSI) and sodium nitroprusside (SNP) (20 μg 0.2 μL -1) a NO donor agent. We have also investigated the central role of losartan and PD123349 (20 nmol 0.2 μL -1), AT 1 and AT 2, respectively (selective non peptide ANG II receptor antagonists), in the pressor effect of ANG II (25 pmol 0.2 μL -1) injected into the MnPO. Male Wistar rats weighting 200-250 g, with cannulae implanted into the MnPO were utilized. Losartan injected into the MnPO, prior to ANG II, blocked the pressor effect of ANGII. PD 123319 only decreased the pressor effect of ANG II. Rats pre-treated with either 50 μg 0.2 μL -1 or 100 μg 0.2 μL -1 of nifedipine, followed by 25 pmol 0.2 μL -1 of ANG II, decreased ANG II-pressor effect. L-NAME potentiated the pressor effect of ANG II. 7-NIT injected prior to ANG II into the MnPO also potentiated the pressor effect of ANGII but with less intensity than that of L-NAME. SNP injected prior to ANG II blocked the pressor effect of ANG II. The potentiation action of L-NAME and 7-NIT on ANG II-pressor effect was blocked by prior injection of nifedipine. The results described in this study provide evidence that calcium channels play important roles in central ANG II-induced pressor effect. The structures containing NO in the brain, such as MnPO, include both endothelial and neuronal cells, which might be responsible for the influence of nifedipine on the pressor effect of ANG II. These data have shown the functional relationship between L-Type calcium channel and a free radical gas NO in the MnPO, on the control of ANG II-induced pressor effect acting in AT 1 and AT 2 receptors.

Articaine and mepivacaine efficacy in postoperative analgesia for lower third molar removal: a double-blind, randomized, crossover study

Objective: Comparison of the clinical efficacy of 4% articaine in relation to 2% mepivacaine, both with 1:100,000 epinephrine, in the prevention of postoperative pain after lower third molar removal. Study design: Twenty patients underwent removal of bilateral lower third molars under local anesthesia (articaine or mepivacaine) in 2 separate appointments, in a double-blind, randomized, and crossed manner. Objective and subjective parameters were recorded for paired comparison of postoperative courses. Results: Duration of analgesia provided by articaine and mepivacaine was 198.00 ± 25.86, and 125.40 ± 13.96 min, respectively (P = .02), whereas the duration of anesthesia was 273.80 ± 15.94 and 216.85 ± 20.15 min, respectively (P = .06). Both solutions exerted no important effects upon arterial pressure, heart rate, or oxygen saturation (P > .05). Conclusions: Articaine provides a longer period of analgesic effect and a tendency for a longer period of anesthesia as compared to mepivacaine. The presence of a vasoconstrictor agent in local anesthetic solutions does not seem to influence hemodynamic parameters during lower third molar removal in healthy subjects. © 2006 Mosby, Inc. All rights reserved.

Neurohormonal, hemodynamic, and electrocardiographic evaluations of healthy dogs receiving long-term administration of doxorubicin

Objective - To evaluate diagnostic testing that could be used to establish an early diagnosis of cardiotoxicosis induced by long-term administration of doxorubicin. Animals - 13 adult mixed-breed dogs. Procedures - 7 dogs were administered doxorubicin chloride (30 mg/m2, IV, q 21 d for 168 days [cumulative dose, 240 mg/m2]), and 6 dogs received saline (0.9% NaCl) solution (5 mL, IV, q 21 d for 168 days; control group). Echocardiography, ECG, arterial blood pressure, plasma renin activity (PRA), and plasma concentrations of norepinephrine and brain natriuretic peptide (BNP) were assessed before each subsequent administration of doxorubicin and saline solution. Results - Dogs that received doxorubicin had a significant decrease in R-wave amplitude, compared with values for the control group, from 30 to 210 mg/m2. Doxorubicin-treated dogs had decreases in fractional shortening and left ventricular ejection fraction evident as early as 30 mg/m2, but significant differences between groups were not detected until 90 mg/m2 was reached. There was also a significant increase in PRA (≥ 120 mg/m2) and left ventricular end-systolic and end-diastolic dimensions (≥ 60 and ≥ 180 mg/m2, respectively). Systemic arterial pressure, remaining echocardiographic variables, and concentrations of norepinephrine and BNP had significant variations, but of no clinical importance, during doxorubicin administration. Conclusions and clinical relevance - Doxorubicin-induced cardiotoxicosis developed at 120 mg/m2, but there were no clinical signs of dilated cardiomyopathy or congestive heart failure. Echocardiography and determination of PRA were able to detect early cardiac alterations during the development of dilated cardiomyopathy, despite apparently differing degrees of sensitivity to development of doxorubicin-induced cardiotoxicosis.

Cardiopulmonary effects of buprenorphine in horses

Objective - To investigate the effects of buprenorphine on cardiopulmonary variables and on abdominal auscultation scores in horses. Animals - 6 healthy adult horses. Procedures - Horses were restrained in stocks and allocated to 2 treatments in a randomized crossover design, with 1-week intervals between each treatment. Saline (0.9% NaCl) solution was administered IV as a control, whereas buprenorphine (10 μg/kg, IV) was administered to the experimental group. Cardiopulmonary data were collected for 120 minutes after buprenorphine or saline solution administration. Abdominal auscultation scores were monitored for 2 and 12 hours after drug administration in the control and experimental groups, respectively. Results - Following control treatment, horses remained calm while restrained in the stocks and no significant changes in cardiopulmonary variables were observed throughout the study. Buprenorphine administration caused excitatory phenomena (restlessness and head shaking). Heart rate, cardiac index, and arterial blood pressure were significantly increased after buprenorphine administration until the end of the observational period (120 minutes). Minimal changes were found in arterial blood gas tensions. Abdominal auscultation scores decreased significantly from baseline for 4 hours after buprenorphine administration. Conclusions and Clinical Relevance - Buprenorphine induced excitement and hemodynamic stimulation with minimal changes in arterial blood gas tensions. These effects may impact the clinical use of buprenorphine in horses. Further studies are indicated to investigate the effects of buprenorphine on gastrointestinal motility and fecal output.

Cardiovascular responses produced by central injection of hydrogen peroxide in conscious rats

Reactive oxygen species (ROS) have been shown to modulate neuronal synaptic transmission and may play a role on the autonomic control of the cardiovascular system. In this study we investigated the effects produced by hydrogen peroxide (H 2O 2) injected alone or combined with the anti-oxidant agent N-acetil-l-cysteine (NAC) or catalase into the fourth brain ventricle (4th V) on mean arterial pressure and heart rate of conscious rats. Moreover the involvement of the autonomic nervous system on the cardiovascular responses to H 2O 2 into the 4th V was also investigated. Male Holtzman rats (280-320 g) with a stainless steel cannula implanted into the 4th V and polyethylene cannulas inserted into the femoral artery and vein were used. Injections of H 2O 2 (0.5, 1.0 and 1.5 μmol/0.2 μL, n = 6) into the 4th V produced transient (for 10 min) dose-dependent pressor responses. The 1.0 and 1.5 μmol doses of H 2O 2 also produced a long lasting bradycardia (at least 24 h with the high dose of H 2O 2). Prior injection of N-acetyl-l-cysteine (250 nmol/1 μL/rat) into the 4th V blockade the pressor response and attenuated the bradycardic response to H 2O 2 (1 μmol/0.5 μL/rat, n = 7) into the 4th V. Intravenous (i.v.) atropine methyl bromide (1.0 mg/kg, n = 11) abolished the bradycardia but did not affect the pressor response to H 2O 2. Prazosin hydrochloride (1.0 mg/kg, n = 6) i.v. abolished the pressor response but did not affect the bradycardia. The increase in the catalase activity (500 UEA/1 μL/rat injected into the 4th V) also abolished both, pressor and bradycardic responses to H 2O 2. The results suggest that increased ROS availability into 4th V simultaneously activate sympathetic and parasympathetic outflow inducing pressor and bradycardic responses. © 2006 Elsevier Inc. All rights reserved.

Vascular hyporeactivity to angiotensin II induced by Escherichia coli endotoxin is reversed by Nω-Nitro-L-Arginine, an inhibitor of nitric oxide synthase

Septic shock or sepsis is reported to be one of the major causes of death when followed by systemic infectious trauma in humans and other mammals. Its development leads to a large drop in blood pressure and a reduction in vascular responsiveness to physiological vasoconstrictors which, if not contained, can lead to death. It is proposed that this vascular response is due to the action of bacterial cell wall products released into the bloodstream by the vascular endothelium and is considered a normal response of the body's defenses against infection. A reduction in vascular reactivity to epinephrine and norepinephrine is observed under these conditions. In the present study in rats, the aim was to assess whether those effects of hypotension and hyporeactivity are also related to another endogenous vasoconstrictor, angiotensin II (AII). We evaluated the variation in the power of this vasoconstrictor over the mean arterial pressure in anesthetized rats, before and after the establishment of hypotension by Escherichia coli endotoxin (Etx). Our results show that in this model of septic shock, there is a reduction in vascular reactivity to AII and this reduction can be reversed by the inhibitor of nitric oxide synthase, Nω-Nitro-L- Arginine (NωNLA). Our results also suggest that other endogenous factors (not yet fully known) are involved in the protection of rats against septic shock, in addition to the L-arginine NO pathway.

Correlação de diferentes períodos de jejum com níveis séricos de cortisol, glicemia plasmática, estado clínico e equilíbrio ácido-base em case submetidos à anestesia geral inalatória

This study correlated the solid preoperative fasting periods with plasma glycemia, serum cortisol, condition clinic and acid-base balance in dogs submitted to inhalation of general anaesthesia. Eight adults, animals were distributed into three groups in accordance with solid preoperative fasting: group 1 (12 hours), group 2 (18 hours) and group 3 (24 hours). Gastric emptying was observed and following this animals were submitted to the same anesthetic procedure. Heart and respiratory rate, rectal temperature, capillary refill time, percent hydration and noninvasive arterial pressure determined before and after Acepromazine and every 10 minutes during anaesthesia, included ETCO 2; values blood gas (pH, PaCO 2, PaO 2, HCO 3, TCO 2, SaO 2, BE), glycemic and serum cortisol were analyzed before MPA and each 30 minutes during anaesthesia. In recovery anaesthetic, glycemia and serum cortisol were repeated. During anaesthesia there were little cardiovascular and respiratory alteration not having interference of the preoperative fasting periods. Animals with 12 hours of the preoperative fasting showed a higher rise in glycemia levels than others groups in recovery anaesthetic. Serum cortisol wasn't influenced by fasting. Solid preoperative fasting independent of the duration describe a discreet respiratory alkalosis. All animals showed good clinical condition in all three groups. Solid preoperative fasting of the 18 hours is recommended to ensure a complete absence of the solid food contents in stomach.

Contribuição ao entendimento da patogenia da sepse

The most frequent cause of vasodilatory shockis outcome from sepsis, a systemic inflammatory response to infection, characterized by hypotension, hyporeactivity to the catecholamines and disseminated intravascular coagulation. The commonest cause of sepsis has reported to be infection with Gram-negative bacteria, typically E. coli, resulting in the release of lipopolysaccharide (endotoxin) from the bacterial outer membrane during autolysis or death of these microorganisms, with the involvement of many mediators, including nitric oxide. Later it was found that plasma levels of vasopressin in sepsis patients were abnormally low and observed that some patients with advanced septic shock were extremely sensitive to the activity actions of exogenous vasopressin.

Efeito hipotensor do extrato aquoso de alpiste (Phalaris canariensis L.) em ratos

The plant species Phalaris canariensis, known as canary grass, is widely used in folk medicine as diuretic, as well as in culinary and animal feed. In this study, the effect of P. canariensis aqueous extract (AE) on water flow (V) and sodium renal excretion (Qe (Na+)) was evaluated in anesthetized Wistar rats. Arterial pressure alterations (AP) were also assessed. Two groups were studied: Control group (CON) - oral administration of 1.0 mL distilled water, and Experimental group (EA) - oral administration of 1.0 mL P. canariensis aqueous extract 40%. Rats were anesthetized and subjected to cannulation of trachea (for better pulmonary ventilation), left carotid artery (for arterial pressure measurement) and urinary bladder (for urine collection). Control animals did not present significant alterations (p>0.05) in all analyzed parameters after water administration. EA group had a significant arterial pressure reduction at 60 minutes (31.4%) and 90 minutes (49.1%) after the extract administration (p<0.05). Renal parameters did not have any significant alteration (p>0.05). In this study, P. canariensis aqueous extract had a hypotensive effect in anesthetized Wistar rats, without renal alterations.

Effects of pentoxifylline and n-acetylcysteine on injuries caused by ischemia and reperfusion of splanchnic organs in rats

Aim. Occlusion and reperfusion of splanchnic arteries cause local and systemic changes due to the release of cytotoxic substances and the interaction between neutrophils and endothelial cells. This study evaluated the role of pentoxifylline (PTX) and n-acetylcysteine (NAC) in the reduction of ischemia, reperfusion shock and associated intestinal injury. Methods. Sixty rats were divided into 6 groups of 10 animals. Rats in three groups underwent mesenteric ischemia for 30 minutes followed by 120 minutes of reperfusion, and were treated with saline (SAL-5 mL/kg/ h), pentoxifylline (PTX-50 mg/kg) or n-acetylcysteine (NAC-430 mg/kg/h). The other 3 groups underwent sham ischemia and reperfusion (I/R) and received the same treatments. Hemodynamic, biochemical and histological parameters were evaluated. Results. No significant hemodynamic or intestinal histological changes were seen in any sham group. No histological changes were found in the lung or liver of animals in the different groups. There was a progressive decrease in mean arterial blood pressure, from mean of 111.53 mmHg (30 minutes of ischemia) to 44.30±19.91 mmHg in SAL-I/R. 34.52±17.22 mmHg in PTX-I/R and 33.81±8.39 mmHg in NAC-I/R (P<0.05). In all I/R groups, there was a progressive decrease in: aortic blood flow, from median baseline of 19.00 mL/min to 2.50±5.25 mL/min in SAL-I/ R; 2.95±6.40 mL/min in PTX-I/R and 3.35±3.40 mL/min in NAC-I/R (P<0.05); in the heart rate, from mean baseline of 311.74 bpm to 233.33±83.88 bpm in SAL-I/R, 243.20±73.25 bpm in PTX-I/R and 244.92±76.05 bpm in NAC-I/R (P<0.05); and esophageal temperature, from mean baseline of 33.68°C to 30.53±2.05°C in SAL-I/R, 30.69±2.21°C in PTX-I/R and 31.43±1.03°C in NAC-I/R (P<0.05). In the other hand, there was an attenuation of mucosal damage in the small intestine of the animals receiving PTX, and only in the ileum of the animals receiving NAC. No changes were found in ileum or plasma malondialdehyde levels in any group. Conclusion. PTX was more efficient in reducing histological lesions than NAC, but neither treatment prevented hemodynamic changes during splanchnic organs I/R.

Efeitos sedativo e cardiorrespiratório da administração da metadona, isoladamente ou em associação à acepromazina ou xilazina, em gatos

Six cats weighting 3.3±0.3 kg were randomly allocated to 6 treatments, with at least one-week intervals. The cats received intramuscular administration of physiological saline (control), methadone (0.3 mg/ kg), acepromazine (0,1 mg/kg), xylazine (1.0 mg/kg), acepromazine (0.05 mg/kg) plus methadone (0.3 mg/kg) or xylazine (0.5 mg/kg) plus methadone (0.3 mg/kg). Heart rate (HR), respiratory rate (RR), indirect systolic arterial pressure (SAP), rectal temperature, sedation score and pedal withdrawal reflex were evaluated before (baseline) and at selected intervals after treatment administration for 90 minutes. Respiratory rate, HR and rectal temperature decreased in cats given xylazine or xylazine plus methadone. In 1 out of 6 cats given xylazine and 2 out of 6 cats given xylazine/methadone, pedal withdrawal reflex was absent. In cats given 0.1 mg/kg of acepromazine, SAP decreased compared to baseline. Sedation scores were greater in cats given xylazine or xylazine plus methadone. Methadone alone or in combination with acepromazine did not produce a satisfactory degree of sedation and resulted in signs of excitement in some of the cats. Methadone alone or combination with acepromazine was not considered an effective protocol when moderate to deep sedation is required in cats. Methadone in combination with xylazine produces moderate to deep sedation, being this effect comparable to that achieved with a higher dose of xylazine alone.

Contribuição do uso de medicamentos para a admissão hospitalar

According to the Word Health Organization, adverse drug reactions (ADR) are any harmful and non intentional answer which occurred in doses normally used in human beings. The ADR can be responsible for 2.4% to 11.5% of hospital admissions. Therefore, this study aimed at knowing the admitted patient's demographic profile due to possible ADR, identifying the most frequent drugs and complaints, and evaluating the incidence of hospital admission related to drug use. Patients who were 18 years old or more and were admitted during a period of one month to a medical clinical of a general hospital were interviewed for one month about drug use before being admitted, as well as regarding to the complaint which led them to hospital. These information were analyzed according to official data, like MICROMEDEX® and WHO criteria as well. It was observed that the admission due to drug use occurred in most part of the cases in elderly [47.5% (66/139)] and women [62% (87/139)]. The most frequent drugs used were: omeprazole (16), analgesics (31), antihypertensive (31), simvastatin (7) and formoterol fumarate (6), and the symptoms were normally associated to the digestive (20.5%), circulatory (20.2%), respiratory (18.2%) and central nervous systems (13.9%). It was estimated that 15.5% (139/897) of the hospital admission occurred possibly due to the drug use. The data found by present study suggests some strategies in order to prevent ADR in the context of primary health care services, such as monitoring drug therapy, manly for patients with chronic diseases, elderly and polimedicated people; and pharmaceutical care including dispensation and purchasing of the drugs, a lot of them dispensed over the counter (OTC).

Effect of 6-months of physical exercise on the nitrate/nitrite levels in hypertensive postmenopausal women

Background: Evidences have showed that the incidence of arterial hypertension is greater in postmenopausal women as compared to premenopausal. Physical inactivity has been implicated as a major contributor to weight gain and abdominal obesity in postmenopausal women and the incidence of cardiovascular disease increases dramatically after menopause. Additionally, more women than men die each year of coronary heart disease and are twice as likely as men to die within the first year after a heart attack. A healthy lifestyle has been strongly associated with the regular physical activity and evidences have shown that physically active subjects have more longevity with reduction of morbidity and mortality. Nitric oxide (NO) produced by endothelial cells has been implicated in this beneficial effect with improvement of vascular relaxing and reduction in blood pressure in both laboratory animals and human. Although the effect of exercise training in the human cardiovascular system has been largely studied, the majority of these studies were predominantly conducted in men or young volunteers. Therefore, the aim of this work was to investigate the effects of 6 months of dynamic exercise training (ET) on blood pressure and plasma nitrate/nitrite concentration (NOx-) in hypertensive postmenopausal women. Methods: Eleven volunteers were submitted to the ET consisting in 3 days a week, each session of 60 minutes during 6 months at moderate intensity (50% of heart rate reserve). Anthropometric parameters, blood pressure, NOx- concentration were measured at initial time and after ET. Results: A significant reduction in both systolic and diastolic blood pressure values was seen after ET which was accompanied by markedly increase of NOx- levels (basal: 10 ± 0.9; ET: 16 ± 2 μM). Total cholesterol was significantly reduced (basal: 220 ± 38 and ET: 178 ± 22 mg/dl), whereas triglycerides levels were not modified after ET (basal: 141 ± 89 and ET: 147 ± 8 mg/dl). Conclusion: Our study shows that changing in lifestyle promotes reducftion of arterial pressure which was accompanied by increase in nitrite/nitrate concentration. Therefore, 6-months of exercise training are an important approach in management arterial hypertension and play a protective effect in postmenopausal women. © 2009 Zaros et al; licensee BioMed Central Ltd.

Cardiac baroreflex is already blunted in eight weeks old spontaneously hypertensive rats

Background. The literature did not evidence yet with which age spontaneously hypertensive rats (SHR) start to present baroreflex reduction. We endeavored to evaluate the baroreflex function in eight-week-old SHR. Methods. Male Wistar Kyoto (WKY) normotensive rats and SHR aged eight weeks were studied. Baroreflex was calculated as the variation of heart rate (HR) divided by the mean arterial pressure (MAP) variation (HR/MAP) tested with a depressor dose of sodium nitroprusside (SNP, 50 g/kg) and with a pressor dose of phenylephrine (PHE, 8 g/kg) in the right femoral venous approach through an inserted cannula in the animals. Significant differences for p < 0.05. Results. Baseline MAP (p < 0.0001) and HR (p = 0.0028) was higher in SHR. Bradycardic peak was attenuated in SHR (p < 0.0001), baroreflex gain tested with PHE was also reduced in the SHR group (p = 0.0012). PHE-induced increase in MAP was increased in WKY compared to SHR (p = 0.039). Bradycardic reflex responses to intravenous PHE was decreased in SHR (p < 0.0001). Conclusion. Eight weeks old SHR already presents impairment of the parasympathetic component of baroreflex. © 2010 Cisternas et al; licensee BioMed Central Ltd.