Increase In Arterial Blood Pressure Research Articles

Picroside-I attenuated isoproterenol-induced heart damage via modification of cardio-morphology, infarct size and inflammatory cascade

Purpose: To study the effect of picroside-I (PIC-I) on isoproterenol (ISO)-induced heart damage in rats through determination of infarct size, antioxidant enzymes, cardiac/inflammatory and apoptotic markers, as well as cardio-morphology.Methods: A total of 32 rats were divided equally into 4 groups. Rats in normal control group were treated with saline only, while myocardial infarction (MI) rat model was prepared by intraperitoneal (i.p.) injection of ISO at a concentration of 100 mg/kg. Rats pretreated with PIC-Iat dose 10 mg/kg (i.p) for 28 days and administered with isoproterenol. Another group of rats was administered only with PIC-I (10 mg/kg) for 28 days.Results: After 28 days of pretreatment with PIC-I, there were significant increases in arterial blood pressure and cardiac antioxidants, as well as marked decreases in infarct size, cardiac markers, inflammatory markers and apoptotic markers in rats with ISO-induced heart damage, when compared with rats given ISO alone. Rats administered PIC-I showed better histology, with reduced necrosis and prominent cardiac fibers.Conclusion: PIC-1 pre-treatment for 28 days significantly reversed elevations in infarct size, cardiac/inflammatory and apoptotic markers, and also improved antioxidant status and cardiacmorphology in rats with ISO-induced heart damage.
 Keywords: Picroside-I, Isoproterenol, Infarct size, Inflammation, Apoptosis

SAT-192 Eletriptan (RelpaxaTm) Causing False Positive Elevations in Urinary Metanephrine

Background:The diagnosis of pheochromocytoma depends crucially on the demonstration of excessive production of catecholamines. This step, however, is fraught with several difficulties, in particular with false-positive test results. Drugs such as phenoxybenzamine and tricyclic antidepressants are the most frequently associated causes for false-positive results. Other medications are also known to cause a false positive elevation of urinary metanephrines. We are reporting a patient with markedly elevated urine metanephrines associated with the use of Eletriptan hydrobromide (RelpaxaTM), a drug commonly used for treating migraine.Clinical Case:A 29-year-old man with a history of migraine managed on ibuprofen and recently started Eletriptan presented to the emergency room complaining of a 24-hour history of progressively worsening headaches. At the time of initial evaluation his blood pressure was in the 220s/160s with a creatinine of 1.9 mg/dL with unknown baseline. He was managed on an IV nicardipine drip. Due to his young age he underwent an evaluation for secondary causes of his hypertension. Laboratory: normal aldosterone/renin level (ratio was 0.4), normal midnight salivary cortisol and normal thyroid function studies. Urine screening for drug abuse was also negative. A 24-hour urine metanephrine level, while the patient was taking Eletriptan, was markedly elevated (normetanephrine 1341mcg (ref 82–500) and metanephrine level of 2494 mcg (ref 45–290). In contrast, the plasma metanephrines were only mildly elevated (metanephrines level 27 pg/ml (ref 0–62) and normetanephrine level of 255 pg/ml (ref 0–145)). Adrenal CT did not reveal any evidence of adrenal nodules. Additionally a Gallium-68 PET/CT scan did not reveal any evidence of pheochromocytoma or paraganglioma. Eletriptan was discontinued and his blood pressure was controlled on oral medications. Within one week of stopping Eletriptan his urine metanephrines (metanephrine 76 mcg/ 24 hrs, normetanephrine 277 mcg/dL) and plasma metanephrines (metanephrine 39 pg/mL, normetanephrine 148 pg/mL) normalized. Conclusion: The discrepancy between plasma and urine metanephrines in our patient suggests the possibility of a false positive test. Eletriptan, a second generation triptan drug, is a selective 5-hydroxytryptamine 1B/1D receptor agonist and has been shown to reduce carotid arterial blood flow, with only a small increase in arterial blood pressure at high doses. However, Eletriptan has no significant affinity or pharmacological activity at adrenergic α1, α2, or β; dopaminergic D1 or D2; muscarinic; or opioid receptors. It is also interesting to note that Eletriptan use is contraindicated in uncontrolled hypertension. It is possible Eletriptan may affect the assay of urine metanephrines. However, the exact mechanism of Eletriptan causing elevated urine metanephrines in our patient is not clear.

Excessive dietary salt promotes aortic stiffness in murine renovascular hypertension.

Renovascular hypertension is characterized by activation of the renin-angiotensin-aldosterone system, blunted natriuretic responses, and elevated sympathetic nerve activity. Excess dietary salt intake exaggerates arterial blood pressure (ABP) in multiple models of experimental hypertension. The present study tested whether a high-salt diet exaggerated ABP and vascular dysfunction in a 2-kidney, 1-clip (2K1C) murine model. Male C57BL/6J mice (8–12 wk) were randomly assigned, and fed a 0.1% or 4.0% NaCl diet, and instrumented with telemetry units to measure ABP. Then, the 2K1C model was produced by placing a cuff around the right renal artery. Systolic, diastolic, and mean ABP were significantly higher in mice fed 4.0% vs. 0.1% NaCl at 1 wk but not after 3 wk. Interestingly, 2K1C hypertension progressively increased arterial pulse pressure in both groups; however, the magnitude was significantly greater in mice fed 4.0% vs. 0.1% NaCl at 3 wk. Moreover, pulse wave velocity was significantly greater in 2K1C mice fed 4.0% vs. 0.1% NaCl diet or sham-operated mice fed either diet. Histological assessment of aortas indicated no structural differences among groups. Finally, endothelium-dependent vasodilation was significantly and selectively attenuated in the aorta but not mesenteric arteries of 2K1C mice fed 4.0% NaCl vs. 0.1% NaCl or sham-operated control mice. The findings suggest that dietary salt loading transiently exaggerates 2K1C renovascular hypertension but promotes chronic aortic stiffness and selective aortic vascular dysfunction.NEW & NOTEWORTHY High dietary salt exaggerates hypertension in multiple experimental models. Here we demonstrate that a high-salt diet produces a greater increase in arterial blood pressure at 1 wk after induction of 2-kidney, 1-clip (2K1C) hypertension but not at 3 wk. Interestingly, 2K1C mice fed a high-salt diet displayed an exaggerated pulse pressure, elevated pulse wave velocity, and reduced endothelium-dependent vasodilation of the aorta but not mesenteric arteries. These findings suggest that dietary salt may interact with underlying cardiovascular disease to promote selective vascular dysfunction and aortic stiffness.

Frequency and individual severity of arterial blood pressure changes in children and adolescents with attention-deficit/hyperactivity disorder treated with methylphenidate hydrochloride: a prospective non-interventional study

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a common behavioural disorder in childhood. The psychostimulant methylphenidate hydrochloride (MPH) is one of the major pharmacological options for ADHD. MPH is known to result, on...

Early Maladaptive Cardiovascular Responses are Associated with Mortality in a Porcine Model of Hemorrhagic Shock.

Hemorrhage is a leading cause of death on the battlefield. Current methods for predicting hemodynamic deterioration during hemorrhage are of limited accuracy and practicality. During a study of the effects of remote ischemic preconditioning in pigs that underwent hemorrhage, we noticed arrhythmias among all pigs that died before the end of the experiment but not among surviving pigs. The present study was designed to identify and characterize the early maladaptive hemodynamic responses (tachycardia in the presence of hypotension without a corresponding increase in cardiac index or mean arterial blood pressure) and their predictive power for early mortality in this experimental model. Controlled hemorrhagic shock was induced in 16 pigs. Hemodynamic parameters were monitored continuously for 7 h following bleeding. Changes in cardiovascular and laboratory parameters were analyzed and compared between those that had arrhythmia and those that did not. All animals had similar changes in parameters until the end of the bleeding phase. Six animals developed arrhythmias and died early, while 10 had no arrhythmias and survived longer than 6 h or until euthanasia. Unlike survivors, those that died did not compensate for cardiac output (CO), diastolic blood pressure (DBP), and stroke volume (SV). Oxygen delivery (DO2) and mixed venous saturation (SvO2) remained low in animals that had arrhythmia, while achieving certain measures of recuperation in animals that did not. Serum lactate increased earlier and continued to rise in all animals that developed arrhythmias. No significant differences in hemoglobin concentrations were observed between groups. Despite similar initial changes in variables, we found that low CO, DBP, SV, DO2, SvO2, and high lactate are predictive of death in this animal model. The results of this experimental study suggest that maladaptive responses across a range of cardiovascular parameters that begin early after hemorrhage may be predictive of impending death, particularly in situations where early resuscitative treatment may be delayed.

Beyond OIRD: The Multiple Negative Effects of Systemic Fentanyl in Adult Goats

Opioids are effective analgesics but are addictive and negatively impact multiple physiologic functions. Opioid abuse has reached epidemic levels and led to an exponential increase in deaths and societal costs, with a disproportionate impact on women. A majority of studies have focused on the depressant effect of opioids on breathing frequency. However, there are data suggesting that opioids cause multiple life‐threatening physiologic effects, but there is a paucity of data assessing the multiple deleterious effects simultaneously in freely behaving mammals. Here we tested the dose‐dependent effects of systemic fentanyl (a major cause of the current opioid crisis) in adult female goats. Systemic fentanyl acutely and dose‐dependently depressed breathing frequency through prolongation of expiratory time while increasing tidal volume similar to effects of fentanyl in humans (J Clin Monit Comput 18: 2004; Eur J. Anest 20: 2003; Br J. Anest 96: 2006). Fentanyl also increased the difference between alveolar and arterial PO2 (A‐a oxygen gradient,) and at high doses increased tonic activity of intercostal and abdominal muscles (consistent with “wooden chest”) while also prolonging post‐inspiratory muscle activation and in rare instances caused obstructive apnea. Beyond these acute (<15 min) effects were prolonged increases in body temperature, metabolic rate, and arterial blood pressure and decreases in heart rate. Furthermore, high dose opioids had long‐lasting effects, including induction of acute withdrawal symptoms, and led to decreased fecal output for >24 h. We conclude that a triad of deleterious effects on cardiorespiratory responses (respiratory frequency depression, A‐a oxygen gradient, and sustained contraction of respiratory muscles) conceivably contribute to hypoxemia induced opioids fatalities. Furthermore, opioids have profound, deleterious effects (withdrawal and constipation) beyond cardiorespiratory control.Support or Funding InformationDepartment of PhysiologyZablocki VA Medical Center

Age‐Related Increase in Extra‐Media Thickness is Associated with Arterial Stiffening and Carotid Blood Pressure

Older age is a primary risk factor associated with future cardiovascular disease (CVD) related events. Age‐related changes in perivascular adipose tissue (PVAT) and vascular remodeling both contribute to arterial stiffening and increased blood pressure which are established CVD risk factors. The non‐invasively measured extra‐media thickness (EMT) is a novel and composite measure, which includes PVAT, arterial adventitia, and the jugular vein that may provide translational insight for these factors contributing to age‐related arterial stiffening and higher blood pressure. However, it is unknown if aging increases EMT and is associated with arterial stiffness and blood pressure. We hypothesized that age‐related increases in EMT will be associated with higher arterial stiffness and blood pressure. Forty participants (young: 8M/12F, 23.2 ± 1.1 yrs and middle‐aged/older: 7M/13F, 60.7 ± 9.4 yrs) underwent measures of blood pressure (brachial; carotid), arterial stiffness (carotid b‐stiffness), EMT via ultrasonography and body composition with dual x‐ray absorptiometry. All measurements were taken in the supine position. Group mean differences between young and middle‐aged/older participants were analyzed with unpaired t‐tests and Pearson correlations were used to assess relations between EMT and arterial stiffness and blood pressure endpoints. Compared to younger participants, middle‐aged/older participants had higher EMT (0.80 ± 0.03 vs. 0.69 ± 0.02 mm), carotid beta stiffness (3.24 ± 0.08 vs. 2.60 ± 0.04), carotid SBP (116.5 ± 4.9 vs. 99.1 ± 2.3 mmHg), and carotid PP (44.6 ± 4.2 vs. 34.8 ± 1.5 mmHg) (all, p<0.05). Brachial SBP was not different between groups (p>0.05). Carotid beta stiffness (r= 0.410), carotid SBP (r= 0.501), and carotid PP (r= 0.5037) were all positively correlated with EMT for the entire cohort (all, p<0.05). Our findings indicate that there is an age‐related increase in EMT that is associated with both carotid arterial stiffness and pressure. These data suggest that increases in arterial stiffness and blood pressure with advancing age may be attributable, in part, to increases in EMT, which may be due to changes in PVAT and arterial adventitial remodeling. Therefore, EMT, a potential surrogate for PVAT and arterial remodeling, may provide novel insight into age‐related arterial stiffening, higher blood pressure and increased CVD risk with aging.

Clinical Course of Coronary Heart Disease Concomitant with Asthma

The research purpose: to study features of clinical process of a coronary heart disease when it combines with a bronchial asthma.The materials and methods: 180 people were included in the research, 90 of them suffer from both CHD and BA (the first group), and also 90 people have only CHD without BA (the second group). The examination included complaint collection process, studying medical history, medical examination, percussion, auscultation, blood pressure measurement with the Korotkov’s method twice a day (in the morning and in the evening), heart rate measurement, 24-hour Holter ECG monitoring, echodoplercardiography. Besides, standard laboratory biochemical testing, including total cholesterol and lowdensity lipoprotein cholesterol, were made with the enzymatic colorimetric method.The results. Dyspnoea is the main complaint among 86 patients with both CHD and asthma, humans have (95,5%), moreover, dyspnoea combines with heartbeating in 73,8%, and is accompanied by angina pectoris only in 20%. There is a significant difference between systolic and diastolic blood pressure (р=0,001) that becomes higher if CHD combines with asthma. The signs of left ventricular and interventricular septum hypertrophy were discovered in the first group, these signs statistically significantly differ from the ones in the second group. The medium pulmonary arterial pressure is significantly higher in the combined group than in the group with only CHD (р=0,001). It is revealed with 24-hour Holter ECG monitoring that cases of myocardial ischemia are more frequent in the group which consists of patients with CHD. Besides, duration of ischemic depression per day is longer in this group too. It might be that if patients have both CHD and asthma they do not reach an ischemic threshold because of dyspnoea due to a respiratory failure.The conclusion. According to our findings bronchial asthma occurs among patients with coronary heart disease in 16.6% of cases. It is a distinctive feature of a bronchial asthma associated with coronary heart disease, that a patient often complaints to dyspnea (cardiopulmonary) and palpitation, increase in arterial blood pressure and heart rate, which appropriately indicates the activation of rennin-angiotensin-aldosteron and sympathicoadrenal systems. It requires the inclusion of appropriate drug groups in the treatment of patients.

Clinical Course of Coronary Heart Disease Concomitant with Asthma

The research purpose: to study features of clinical process of a coronary heart disease when it combines with a bronchial asthma.The materials and methods: 180 people were included in the research, 90 of them suffer from both CHD and BA (the first group), and also 90 people have only CHD without BA (the second group). The examination included complaint collection process, studying medical history, medical examination, percussion, auscultation, blood pressure measurement with the Korotkov’s method twice a day (in the morning and in the evening), heart rate measurement, 24-hour Holter ECG monitoring, echodoplercardiography. Besides, standard laboratory biochemical testing, including total cholesterol and lowdensity lipoprotein cholesterol, were made with the enzymatic colorimetric method.The results. Dyspnoea is the main complaint among 86 patients with both CHD and asthma, humans have (95,5%), moreover, dyspnoea combines with heartbeating in 73,8%, and is accompanied by angina pectoris only in 20%. There is a significant difference between systolic and diastolic blood pressure (р=0,001) that becomes higher if CHD combines with asthma. The signs of left ventricular and interventricular septum hypertrophy were discovered in the first group, these signs statistically significantly differ from the ones in the second group. The medium pulmonary arterial pressure is significantly higher in the combined group than in the group with only CHD (р=0,001). It is revealed with 24-hour Holter ECG monitoring that cases of myocardial ischemia are more frequent in the group which consists of patients with CHD. Besides, duration of ischemic depression per day is longer in this group too. It might be that if patients have both CHD and asthma they do not reach an ischemic threshold because of dyspnoea due to a respiratory failure.The conclusion. According to our findings bronchial asthma occurs among patients with coronary heart disease in 16.6% of cases. It is a distinctive feature of a bronchial asthma associated with coronary heart disease, that a patient often complaints to dyspnea (cardiopulmonary) and palpitation, increase in arterial blood pressure and heart rate, which appropriately indicates the activation of rennin-angiotensin-aldosteron and sympathicoadrenal systems. It requires the inclusion of appropriate drug groups in the treatment of patients.

Central CYP1B1 (Cytochrome P450 1B1)-Estradiol Metabolite 2-Methoxyestradiol Protects From Hypertension and Neuroinflammation in Female Mice.

Previously, we showed that peripheral administration of 2-ME (2-methoxyestradiol), a CYP1B1 (cytochrome P450 1B1)-catechol-O-methyltransferase (COMT) generated metabolite of E2 (17β-Estradiol), protects against angiotensin II-induced hypertension in female mice. The demonstration that central E2 inhibits angiotensin II-induced hypertension, together with the expression of CYP1B1 in the brain, led us to hypothesize that E2-CYP1B1 generated metabolite 2-ME in the brain mediates its protective action against angiotensin II-induced hypertension in female mice. To test this hypothesis, we examined the effect of intracerebroventricularly (ICV) administered E2 in ovariectomized (OVX)-wild-type (Cyp1b1+/+) and OVX-Cyp1b1-/- mice on the action of systemic angiotensin II. ICV-E2 attenuated the angiotensin II-induced increase in mean arterial blood pressure, impairment of baroreflex sensitivity, and sympathetic activity in OVX-Cyp1b1+/+ but not in ICV-injected short interfering (si)RNA-COMT or OVX-Cyp1b1-/- mice. ICV-2-ME attenuated the angiotensin II-induced increase in blood pressure in OVX-Cyp1b1-/- mice; this effect was inhibited by ICV-siRNA estrogen receptor-α (ERα) and G protein-coupled estrogen receptor 1 (GPER1). ICV-E2 in OVX-Cyp1b1+/+ but not in OVX-Cyp1b1-/- mice and 2-ME in the OVX-Cyp1b1-/- inhibited angiotensin II-induced increase in reactive oxygen species production in the subfornical organ and paraventricular nucleus, activation of microglia and astrocyte, and neuroinflammation in paraventricular nucleus. Furthermore, central CYP1B1 gene disruption in Cyp1b1+/+ mice by ICV-adenovirus-GFP (green fluorescence protein)-CYP1B1-short hairpin (sh)RNA elevated, while reconstitution by adenovirus-GFP-CYP1B1-DNA in the paraventricular nucleus but not in subfornical organ in Cyp1b1-/- mice attenuated the angiotensin II-induced increase in systolic blood pressure. These data suggest that E2-CYP1B1-COMT generated metabolite 2-ME, most likely in the paraventricular nucleus via estrogen receptor-α and GPER1, protects against angiotensin II-induced hypertension and neuroinflammation in female mice.

Regulatory safety pharmacology evaluation of BIA 10-2474

The present paper describes the regulatory safety pharmacology studies that were carried out to support the clinical trial application for BIA 10–2474. Animal studies complied with worldwide regulatory guidelines (e.g. EEC Council Directive 75/318/EEC and subsequent amendments). Oral administration of BIA 10–2474 at doses of 30, 100 and 300 mg/kg to male Han Wistar rats did not cause any significant physiological or behavioral changes, affect the respiration rate or the tidal volume, the gastrointestinal transit, urinary output volume or pH, nor urinary sodium, potassium or chloride excretion. BIA 10–2474, at 30 μg/mL, slightly, but significantly, reduced the hERG outward tail currents by 10.62%, but had no effect at 1, 3 or 10 μg/mL. BIA 10–2474 (1.5, 4.5 and 15 μg/mL) had no substantial effects on resting membrane potential (RMP), maximal upstroke velocity (Vmax), action potential amplitude (APA), action potential duration at 30%, 60% and 90% or action potential triangulation over the 30-min superfusion period in the dog isolated Purkinje fiber. In conscious dogs monitored by telemetry, BIA 10–2474 (20, 50 and 100 mg/kg p.o.) did not significantly modify arterial blood pressure as compared with controls (inter-group comparison), although a tendency toward an increase in arterial blood pressure was observed at 100 mg/kg, with systolic blood pressure being the most affected parameter. In conclusion, BIA 10–2474 had no adverse effects on any of the major vital organ systems, and, unfortunately, the data shed no further light on the mechanism(s) responsible for the clinical trial accident with BIA 10–2474.

Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow

Astrocytes provide neurons with essential metabolic and structural support, modulate neuronal circuit activity and may also function as versatile surveyors of brain milieu, tuned to sense conditions of potential metabolic insufficiency. Here we show that astrocytes detect falling cerebral perfusion pressure and activate CNS autonomic sympathetic control circuits to increase systemic arterial blood pressure and heart rate with the purpose of maintaining brain blood flow and oxygen delivery. Studies conducted in experimental animals (laboratory rats) show that astrocytes respond to acute decreases in brain perfusion with elevations in intracellular [Ca2+]. Blockade of Ca2+-dependent signaling mechanisms in populations of astrocytes that reside alongside CNS sympathetic control circuits prevents compensatory increases in sympathetic nerve activity, heart rate and arterial blood pressure induced by reductions in cerebral perfusion. These data suggest that astrocytes function as intracranial baroreceptors and play an important role in homeostatic control of arterial blood pressure and brain blood flow.

"Is the Widening of Pulse Pressure and Hypertension in the Elderly Due in Large Measure to an Unrecognized Hypomagnesemia, Downregulation of Telomerase and Progressive Release of Ceramides and Platelet-Activating Factor?"

It is generally agreed that age-related increases in arterial blood pressure (ABP) are mainly a reflection of an increase in systolic..

Chloropyramine and Ranitidine as a combination of H1 and H2- antihistamines in the additive therapy of anaphylaxis

Introduction: Current international guidelines recommend H1 and H2- antihistamines as a second or third- line drugs for the management of anaphylaxis. Aim: To present positive cardiovascular and dermatological effects of Chloropyramine and Ranitidine as the combination of H1 and H2- antihistamines in additive therapy of anaphylaxis. Patients and methods: In a retrospective study two groups of 146 patients who met the NIAID/FAAN criteria for the diagnosis of anaphylaxis were compared. Experimental group consisted of 62 patients who received combination of Chloropyramine H1- antihistamines and Ranitidine H2- antihistamines. Control group consisted of 84 patients who received only Chloropyramine H1- antihistamines. Results: A statistically significant differences of diastolic pressure and central pulse (p< 0.001), a higher values of diastolic pressure, and a lower values of central pulse in the experimental group of patients were recorded at the end of the prehospital treatment of anaphylaxis. The increase in the mean arterial blood pressure at the end of the treatment is higher in the experimental group compared to the initial values, with an average difference of 15 mmHg (%95 CI= 7,95-21,95). Total prehospital time and time recovery of the skin urticaria and itch was shorter in the experimental group for 18 minutes (95% CI= 11,95-25,95). Conclusion: Positive cardiovascular effects and a faster resolving of the skin symptoms justify the use of combination Chloropyramine and Ranitidine as an additive therapy of anaphylaxis that is not life- threatening, and of a rapid progression.

Effect of Aqueous Extract of Adansonia digitata Stem Bark on the Development of Hypertension in L-NAME-Induced Hypertensive Rat Model.

Background Adansonia digitata is a plant used against cardiovascular disorders in African folk medicine. We assessed the effects of the aqueous extract of its stem bark on the development of hypertension in L-NAME-induced hypertensive rats. Methods The animals were administered L-NAME once daily for 3 weeks (25 mg/kg, i.p.), concomitantly with aqueous extract of A. digitata stem bark (100 and 200 mg/kg, p.o.) or captopril (20 mg/kg, p.o.). Then, hemodynamic and electrocardiographic parameters, oxidative stress markers, and the lipid profile were assessed in the blood and heart, aorta, and kidney homogenates, and histopathological analyses were performed. Results L-NAME-induced hypertensive control animals, but not the animals concomitantly treated with A. digitata extract, displayed increases in the mean arterial blood pressure (21.64% difference, p < 0.001, vs. dose 200 mg/kg), systolic arterial blood pressure (21.33%, p < 0.001), and the diastolic arterial blood pressure (21.84%, p < 0.001). In addition, hypertensive control animals displayed (i) increases in serum triglycerides, total cholesterol, LDL, and creatinine levels, malondialdehyde and transaminase activities, and atherogenic index; (ii) decreases in serum HDL, catalase, reduced glutathione, and nitric oxide; and (iii) aorta wall thickening, inflammatory cell infiltration, and cell loss in the cardiac muscle and renal tissues. As captopril, the extract prevented hypertension-like changes in lipid profile, cardiac, hepatic, and renal affection indicators, and oxidative stress markers. Conclusion Our findings suggest that the extract of A. digitata has antihypertensive and antioxidant effects in L-NAME-induced hypertension rat models. These effects partly justify the traditional medicine use against cardiovascular disorders.

How does an athlete’s heart react to studying at university?

2 groups of participants have been studied: I – student-athletes; II – students and postgraduate students, not involved in sport. The functional status of the heart has been studied in three conditions: at rest, during the cognitive test, and under local static load (the wrist dynamometer). The electroencephalography has also been applied. Results demonstrated a statistical decrease in wrist endurance in all participants during the academic year. They proved fatigue development. A pronounced increase of heart rate and arterial blood pressure, as well as the increase of heart rate variability mode and stress index under local load and during the cognitive test, proved the development of the heart functional stress, especially in athletes. Electroencephalography data prove the central origin of adaptation reactions both to mental and to local muscular activity. Disease prevention and health improvement measures are necessary for university students actively involved in sport. One of such measures is relaxation exercises aimed at a decrease in functional stress.

Pivotal role of the ventral tegmental area in spontaneous motor activity and concomitant cardiovascular responses in decerebrate rats

Central command, a feedforward signal from higher brain centers, regulates the cardiovascular system in association with exercise. Previous evidence suggests that nucleus (or nuclei) around the midbrain may contribute to generating spontaneous motor activity and concomitant cardiovascular responses. To examine which area within the midbrain is important for the spontaneous and synchronized responses, 18 rats were decerebrated at three levels (pre-midbrain, rostroventral midbrain, and caudal midbrain levels) and paralyzed with a neuromuscular blocker. Individual brain sections showed decerebration rostral to the pre-collicular level in the pre-midbrain preparation and, additionally, removal of the periaqueductal gray in the rostroventral midbrain preparation, and decerebration around the midcollicular level in the caudal midbrain preparation. Spontaneous motor activity occurred at frequency of 69 ± 27 times/h and accompanied increases in heart rate (by 15 ± 4 beats/min) and mean arterial blood pressure (by 54 ± 4 mmHg) in the pre-midbrain preparation. Similar motor and cardiovascular responses took place in the rostroventral midbrain preparation, while such responses hardly occurred in the caudal midbrain preparation. We next examined whether injection of a GABAergic receptor agonist (muscimol) in the ventral tegmental area (VTA) inhibits the spontaneous motor and cardiovascular responses in 6 pre-midbrain preparations. The occurrence of spontaneous motor activity and concomitant cardiovascular responses was inhibited clearly (P < 0.05) by injection of muscimol, but not saline. It is concluded that the VTA plays a pivotal role in the spontaneous and synchronized activation of the motor and cardiovascular systems in decerebrate rats.

The association of the optimal bolus of dexmedetomidine with its favourable haemodynamic outcomes in adult surgical patients under general anaesthesia.

Dexmedetomidine is highly specific α2-adrenoceptor agonist. A single bolus of dexmedetomidine can achieve clinical therapeutic effect. Therefore, it is essential to know the safety margin between the clinical effectiveness dosages of dexmedetomidine and its side effect. A total of 42 patients who underwent elective thyroidectomy were enrolled in this study. Dexmedetomidine was given as a single bolus injection 30 min towards the end of surgery. The up-and-down sequential schedule was used in this study. The starting dose of dexmedetomidine was set at 0.1 μg/kg in the first patient and the next patient would then receive a dose of dexmedetomidine decremented by 0.05 μg/kg if the prior patient's baseline heart rate (HR) had a decrease of ≥20% and/or mean arterial blood pressure (MAP) increase or decrease of ≥20%, otherwise, the following patient would receive an incremental 0.05 μg/kg dose of dexmedetomidine. The analytic techniques of linear, linear-logarithmic, exponential regressions and centred isotonic regression were used to determine the ED50 of dexmedetomidine and the residual standard errors were calculated for the comparison of goodness of fit among the different models. The median (interquartile range [range]) lowest HR was 57 beats/min (53-63.3[46-76]) with an average HR decrease of 8.0 beats/min (5-13 [4 to 23]). The median (interquartile range [range]) highest MAP was 98 mmHg (91.8-105 [83-126]) with a MAP increase of 10.0 mmHg (6.8-18.0 [2-24]). The ED50 (95% confidence interval) from 4 different statistical approaches (linear, linear-logarithmic, exponential regressions and centred isotonic regression) were 0.262 μg/kg (0.243, 0.306), 0.252 μg/kg (0.238, 0.307), 0.283 μg/kg (0.238, 0.307), and 0.278 μg/kg, respectively. Among the 4 models, the exponential regression had the least residual standard error (0.03618). The ED50 derived from 4 statistical models for an intravenous bolus of dexmedetomidine without significant haemodynamic effects was distributed in a narrow range of 0.252-0.283 μg/kg, and the exponential regression was the model to best match the study data.

Dilatation of Retinal Arterioles Induced by Topical Dorzolamide for One Week Is Impaired in Patients with Type 1 Diabetes and Mild Retinopathy

Background: Diabetic retinopathy is characterised by morphological lesions in the retina secondary to disturbances in retinal blood flow. Previous studies have shown that the carbonic anhydrase inhibitor (CAI) dorzolamide can induce immediate dilatation of retinal arterioles and a sustained increase in retinal blood flow in primary open-angle glaucoma. However, the effect of sustained treatment with CAI on retinal arterioles in normal persons and in patients with diabetic retinopathy is unknown. Methods: The Dynamic Vessel Analyzer was used to assess the baseline diameter and the diameter response of retinal arterioles during an increase in arterial blood pressure induced by isometric exercise and during flicker stimulation before and 2 h, 24 h and 1 week after onset of topical treatment with dorzolamide. At each examination the diameter responses were studied before and during breathing in of a hypercapnic gas mixture. Results: Treatment with dorzolamide for 1 week significantly increased the diameter of retinal arterioles in normal persons, and breathing in of a hypercapnic gas mixture reduced this response. The pathological vasodilatation and reduced retinal autoregulation in patients with diabetic retinopathy were unaffected by dorzolamide and hypercapnia. Conclusions: The study suggests a lack of relevance of CAI for the treatment of pathological vasodilatation in early diabetic retinopathy.

Rapid blood pressure increase after renal denervation in anaesthetized rats: interaction of oxidative stress and neuronal nitric oxide synthase.

We showed previously that in anaesthetized rats acute noninvasive renal denervation (DNX) induced an increase in arterial blood pressure (MABP), unlike the usual hypotensive effect. Here we aimed to establish the background of such unusual response, especially the role of oxidative stress as suggested by an earlier study. The contribution of oxidative stress was explored by studying the effects on DNX-induced MABP increase of pretreatment with 4-hydroxy-3-methoxyacetophenone (apocynin, APO), a powerful antioxidant and antihypertensive agent, and N(omega)-propyl-L-arginine (L-NPA), a blocker of neuronal nitric oxide synthase (nNOS). In anaesthetized Wistar rats maintained on standard (STD) or high-salt (HS) diet sequential right- and left-side DNX was performed. MABP responses were examined without pretreatment and after APO (20 mg/day on two preceding days) and L-NPA (1 mg/kg/h throughout experiment), given alone or combined. In untreated rats, bilateral DNX increased MABP by 6% on STD and 15% on HS diet (P < 0.01 or less); the difference between MABP responses was highly significant (P = 0.002). In STD rats APO or APO + L-NPA treatment failed to alter post-DNX MABP increases whereas L-NPA alone reversed the response and a significant 7% decrease occurred. In HS rats APO and L-NPA given alone reversed the MABP response and significant decreases of 14% (P = 0.001) and 8% (P = 0.01), were seen. Surprisingly, with L-NPA + APO pretreatment only abolishment (not reversal) of post-DNX pressure increase occurred. The results suggest that both systemic, intrarenal and brain oxidative stress, and excessive nNOS activity, mostly in the brain, determine the unexpected post-DNX pressure increase.