Significant Increase In Blood Pressure Research Articles

Long-Term Consequences of Complex Living Renal Donation: Is It Safe?

IntroductionAs there is a paucity of literature regarding the long-term outcomes of complex living donors, we conducted this study to assess the effect of kidney donation on the complex living kidney donor. Materials and MethodsThis retrospective study was conducted in Narayan Health Hospital, Kolkata, Eastern India. The cohort consisted of complex living kidney donors who donated kidneys between the years 2007 and 2012. All donors were 60 years old or older, or were younger than 60 years and had comorbidities like hypertension and obesity. After a minimum follow-up of 5 years, all donors underwent evaluation. Data pertaining to hypertension, new-onset diabetes, body mass index (BMI), estimated glomerular filtration rate (eGFR) and albuminuria, and cardiac events were compared from the time of donation till 5 years post-transplant. Results and DiscussionWe found a statistically significant increase in blood pressure, number of antihypertensives used, and mean BMI at follow-up. Diabetes mellitus was developed in 22.3% of donors. The mean GFR also decreased significantly at follow-up. There were 42 elderly donors (≥60 years) and 23 ≤ 59 years of age. There was a significant fall of eGFR in both groups, but the percentage fall was similar in both groups. A significant percentage of donors developed proteinuria, the majority being hypertensives. ConclusionProcurement of kidneys from marginal donors should be done cautiously, and donors should be assessed for morbidity and mortality in the future, as we found a statistically significant deterioration in renal function, blood pressure, and BMI over long-term follow-up.

EFFECT OF ELECTRONIC CIGARETTE SMOKING ON BLOOD PRESSURE IN HYPERTENSIVE PATIENTS. EVALUATION BY NON-INVASIVE CONTINUOUS AMBULATORY BLOOD PRESSURE MEASUREMENT

Objective: The electronic cigarettes (EC) is a device that heats a liquid containing nicotine and flavors into an aerosol for inhalation. There is some evidence from controlled trials that electronic cigarette (EC) may help to stop smoking long-term. However, a large proportion of smokers who successfully quit cigarette smoking continue to use EC for unlimited time, switching from an addiction to another. There is a clear similarity between the detrimental vascular effects of EC and conventional cigarette. Little is known about the acute influence on blood pressure (BP) of nicotine inhalation by EC and it's duration of action in hypertensive subjects. Aim of this study was to evaluate the magnitude and time-course of BP changes during EC smoking. Design and method: This is a randomized, cross-over and placebo controlled study. We evaluated 30 mild-to-moderate hypertensive patients on pharmacological treatment and adequate BP control (< 140/90 mmHg). Patients (22 males, mean age 54 ± 21 years) were former smokers, who quitted tobacco cigarette in favor of EC at least 6 months before. BP and heart rate (HR) were measured by continuous non-invasive ambulatory BP and ECG monitoring (SOMNOtouch NIBP). BP and HR were monitored during a 30 minute rest in the sitting position; during other 30 minutes after smoking EC (inhalation equivalent to 0.8 mg of nicotine of a regular cigarette) or placebo EC (same device, same flavor but no nicotine in the solution). Results: EC vaping was accompanied by significant increase blood pressure, which lasted about 30 minutes (average 28 ± 11 minutes). Compared to placebo the EC smoking increased systolic BP by 9,6 ± 4,1 mmHg, diastolic BP by 7.1 ± 3.9 mmHg and heart rate by 16,4 ± 13 beat per minute. All the differences resulted statistically significant (Student's t test P < 0.05). Conclusions: Under these experimental conditions, EC smoking caused a statistically significant increase in BP and HR in hypertensive patients. This effect seems also clinically relevant since the duration of BP increase was relatively long (28 minutes) and the daily number of inhalations, in EC smokers, is usually high (> 20).

Endothelial Cell Tetrahydrobiopterin Modulates Sensitivity to Ang (Angiotensin) II-Induced Vascular Remodeling, Blood Pressure, and Abdominal Aortic Aneurysm.

GTPCH (GTP cyclohydrolase 1, encoded by Gch1) is required for the synthesis of tetrahydrobiopterin; a critical regulator of endothelial NO synthase function. We have previously shown that mice with selective loss of Gch1 in endothelial cells have mild vascular dysfunction, but the consequences of endothelial cell tetrahydrobiopterin deficiency in vascular disease pathogenesis are unknown. We investigated the pathological consequence of Ang (angiotensin) II infusion in endothelial cell Gch1 deficient (Gch1fl/fl Tie2cre) mice. Ang II (0.4 mg/kg per day, delivered by osmotic minipump) caused a significant decrease in circulating tetrahydrobiopterin levels in Gch1fl/fl Tie2cre mice and a significant increase in the Nω-nitro-L-arginine methyl ester inhabitable production of H2O2 in the aorta. Chronic treatment with this subpressor dose of Ang II resulted in a significant increase in blood pressure only in Gch1fl/fl Tie2cre mice. This finding was mirrored with acute administration of Ang II, where increased sensitivity to Ang II was observed at both pressor and subpressor doses. Chronic Ang II infusion in Gch1fl/fl Tie2ce mice resulted in vascular dysfunction in resistance mesenteric arteries with an enhanced constrictor and decreased dilator response and medial hypertrophy. Altered vascular remodeling was also observed in the aorta with an increase in the incidence of abdominal aortic aneurysm formation in Gch1fl/fl Tie2ce mice. These findings indicate a specific requirement for endothelial cell tetrahydrobiopterin in modulating the hemodynamic and structural changes induced by Ang II, through modulation of blood pressure, structural changes in resistance vessels, and aneurysm formation in the aorta.

Effects of δ-tocotrienol on ochratoxin A-induced nephrotoxicity in rats.

Ochratoxin A (OTA), is a natural contaminant of the food chain worldwide involved in the development of different type of cancers in animals and humans. Several studies suggested that oxidative damage might contribute to increase the cytotoxicity and carcinogenicity capabilities of OTA. The aim of this study was to evaluate the possible protective effect of δ-tocotrienol (Delta), a natural form of vitamin E, against OTA-induced nephrotoxicity. Male Sprague-Dawley rats were treated with OTA and/or Delta by gavage for 14 days. Our results shown that OTA treatment induced the increase of reactive oxigen species production correlated to a strong reduction of Glomerular Filtration Rate (GFR) and absoluted fluid reabsorption (Jv) with conseguent significant increase in blood pressure. Consistent, we noted in the kidney of rats treated with OTA, an increase in malondialdheyde and dihydroethidium production and a reduction of the activity of the catalase, superoxide dismutase, and glutathione peroxidase. Conversly, in the rat group subjected to the concomitant treatment OTA plus Delta, we observed the restored effect, compared the OTA treatment group, on blood pressure, GFR, Jv, and all activities of renal antioxidant enzymes. Finally, as far as concern the tissue damage induced by OTA and measured evaluating fibronectin protein levels, we observed that in OTA plus Delta group this effect is not restored. Our findings releval that a mechanism underlying the renal toxicity induced by OTA is the oxidative stress and provide a new rationale to use a Delta in order to protect, at least in part, against OTA-induced nephrotoxicity.

SPECIFICS OF ARTERIAL HYPERTENSION DEVELOPMENT IN PENITENTIARY STRESS CIRCUMSTANCES

Aim. To reveal the specifics of arterial hypertension (AH) development under the circumstances of penitentiary stress.Material and methods. Totally, 107 patients included, among the persons first time imprisoned, comparable by age and gender — almost healthy young males 25-36 y. o. The relation studied, of psychological test and 24-hour blood pressure (BP) profile and Holter ECG, as heart rate variablity, in three groups of participants formed depending on the duration of imprisonment.Results. It was found that psychoemotional state during the first month of imprisonment is characterized by a high level of situational, personality anxiety with predominant depressive symptomatic. This is followed by heart conduction and rhythm pathology. With the time of imprisonment, level of anxiety and depression declines. Also, heart rhythm variability analysis shows significant decrease of value of LF (%) and predomination of VLF (%) in the wave spectrum. The parameters of 24-hour BP show a significant increase of BP at later periods of imprisonment. Daytime BP level shows direct relation with the parameter “duration of imprisonment”, and nocurnal BP — with the level of situational anxiety.Conclusion. Under the circumstances of penitentiary stress, one of the revealed mechanism of AH development is weakening of sympathetic modulation of vegetative innervation of the heart and decline of baroreflectory sensitivity. Increase of the duration of imprisonment and of the level of situational anxiety are the specific factors of penitentiary circumstances that influence AH development in young clinically healthy men.

Cosinor Analysis Reveals Non‐dipping Hypertension in Mixed Background Strain Mice Lacking the Circadian Clock Protein PER1

Cardiovascular disease is the leading cause of death among Americans. Hypertension is the leading risk factor for cardiovascular disease, thus blood pressure (BP) regulation is imperative for maintaining cardiovascular health. BP exhibits a circadian rhythm that is regulated through many mechanisms. Humans experience a BP rhythm resulting in a 10–20% dip in BP during their resting period. Individuals who fail to maintain this dip, termed non‐dippers, are associated with worse cardiovascular outcomes. The circadian clock mechanism, which includes the transcription factors PERIOD, BMAL1, CLOCK, and CRYPTOCHROME, is necessary to maintain this rhythm. Past studies in our lab have shown that global loss of PER1 leads to non‐dipping hypertension in male C57BL/6 mice in response to high salt diet plus an aldosterone analogue desoxycorticosterone pivalate‐salt (DOCP) (Solocinski et al. 2017). The goal of this study was to determine the BP phenotype of Per1 knockout (KO) mice on a salt‐sensitive 129/sv/s1s4 background strain. 129/sv/s1s4 mice were implanted with radiotelemetry devices and maintained in a normal 12‐hour light/dark period. BP was monitored continuously while the mice were subjected to a control diet, a high salt (HS) diet, or a HS diet plus treatment with an aldosterone analogue DOCP. BP rhythms were analyzed through the program Cosinor (www.circadian.org) to determine the mesor, amplitude, and acrophase. When evaluating a cosine wave, the mesor is the midline between the peak and the trough, the amplitude is the measure of the mesor to the peak, and the acrophase is the time point of the peak. These values were then used to discern whether the mice maintained a BP rhythm. The 129/sv/s1s4 Per1 KO experienced a 9‐mmHg increase in BP in response to HS/DOCP (P&lt;0.01, n=8). In contrast, the wild type (WT) mice (n=5) did not experience a significant increase in BP after HS/DOCP. Furthermore, the KO mice had a 2.4‐mmHg decrease in amplitude (P=0.01), whereas the WT mice did not exhibit a significant decrease in amplitude. The WT mice on control diet exhibited a 12.8% dip in BP during their inactive period compared to their active period, which insignificantly decreased to an 11.5% dip on HS/DOCP diet. However, the KO mice on control diet had an 11% dip, which decreased to 5.4% dip on HS/DOCP diet (P&lt;0.05, n=5–8). These data demonstrate that loss of Per1 in male 129/sv/s1s4 mice leads to a non‐dipping phenotype in response to HS/DOCP treatment. Importantly, these findings represent the reproducibility of the non‐dipping hypertension phenotype we previously observed in C57BL/6 mice in a distinct strain on a mixed background.Support or Funding InformationAmerican Physiological Society Undergraduate Summer Fellowship Program; American Society of Nephrology Foundation for Kidney ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Reduction in nitric oxide bioavailability shifts serum lipid content towards atherogenic lipoprotein in rats

Nitric oxide (NO) is major endothelial relaxing factor and reduction in its bioavailabilty has been linked to hypertension. Furthermore, high lipid content is a strong risk factor predisposing to cardiovascular diseases. The principal focus of this study was to investigate the effect of blockade of nitric oxide synthase (NOS) on serum lipid content in rats. Male Wistar rats (150–170 g, n = 15) were randomly divided into two groups designated control (n = 5), and L-Name group (n = 10) and were gavage with distilled water and 60 mg/kg of L-NAME respectively daily for three weeks. After 3 weeks, the L-NAME group was sub-divided into two sub-groups (n = 5 each): L-NAME (60 mg/kg of L-NAME), and L-NAME plus ramipril (LR) (60 mg/kg of L-NAME plus 20 mg/kg of ramipril) and were treated daily for another three weeks. The blood pressure (BP) of the conscious rats was measured by tail-cuff method at the onset, at the third and at the sixth weeks of the experiment; while serum lipid contents and NO were measured at the third and sixth weeks. At the end of the experiment blood sample was drawn by ocular puncture for evaluation of lipid profile and NO, and the animals were later euthanized by overdose of anaesthesia. Data were analyzed using ANOVA at p < 0.05. There was a significant increase in BP, triglyceride, total cholesterol, low density lipoprotein-cholesterol, and atherogenic indices in L-NAME group compared to the control and LR group (p < 0.05); NO and high density lipoprotein-cholesterol was significant lower in the L-NAME group compared to control and LR (p < 0.05). In conclusion, reduction in NO bioavailability alters lipid metabolism, which was rectified by ramipril.

Blood pressure in children with attention deficit/hyperactivity disorder.

Children with attention deficit/hyperactivity disorder (ADHD) are frequently treated with psycho-stimulant agents causing a modest but significant increase in blood pressure and heart rate. The objective of this study was to define blood pressure characteristics in children with ADHD treated with a variety of medications in a community setup. Children registered at a large paediatric clinic in Calgary, AB with documented histories of ADHD were randomly contacted. Consenting participants had standardized office BP measurements, ambulatory blood pressure monitoring (ABPM) studies and were asked to complete the sleep disturbance scale for children (SDSC) questionnaire. Findings were compared with data from the Canadian Health Measures Survey (CMHS). Fifty-five children (47 males) aged 7 to 17 years (average 11.6 ± 2.5 years) with an average BMI z-score of -0.37 ± 1.22 completed the study. All children were medicated, the majority (82%), with various types of stimulant agents. Elevated office BP values were more prevalent than in the CMHS; >90th percentile in 5 (9.1%) and >95th percentile in 3 (5.5%). ABPM confirmed 'white coat hypertension' in 3 (5.5%), masked hypertension in 2 (3.6%) and nondipping in 28 (51%). The SDSC score suggested that 43 (78%) children had disturbed sleep. Logistic regression modelling indicated that nondipping correlated with disturbed sleep. The 'white coat' phenomenon may be responsible for increased prevalence of elevated rest/office BP values in children with ADHD. Prevalent sleep 'non-dipping' in this population is associated with sleep disturbances but clinical significance of this finding requires further investigation.

Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma.

Sunitinib, used widely in metastatic renal cell carcinoma, can result in hypertension, left ventricular dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood. In a multicenter prospective study of 84 metastatic renal cell carcinoma patients, echocardiography, arterial tonometry, and BNP (B-type natriuretic peptide) measures were performed at baseline and at 3.5, 15, and 33 weeks after sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and left ventricular ejection fraction, longitudinal strain, diastolic function (E/e'), and BNP. After 3.5 weeks of sunitinib, mean systolic blood pressure increased by 9.5 mm Hg (95% confidence interval, 2.0-17.1; P=0.02) and diastolic blood pressure by 7.2 mm Hg (95% confidence interval, 4.3-10.0; P<0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid-femoral pulse wave velocity) and resistive load (total peripheral resistance and arterial elastance; all P<0.05) and changes in pulsatile load (total arterial compliance and wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (left ventricular ejection fraction and longitudinal strain). However, baseline total peripheral resistance, arterial elastance, and aortic impedance were associated with worsening diastolic function and filling pressures over time. In patients with metastatic renal cell carcinoma, sunitinib resulted in early, significant increases in blood pressure, arterial stiffness, and resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic but not systolic function.

Comparison of a loading dose of dexmedetomidine combined with propofol or sevoflurane for hemodynamic changes during anesthesia maintenance: a prospective, randomized, double-blind, controlled clinical trial

BackgroundThere may be great individual variability in the hemodynamic effects of this dexmedetomidine. For this reason, the dose must be carefully adjusted to achieve the desired clinical effect. Whether a loading dose of dexmedetomidine produces hemodynamic side effects during the anesthesia maintenance is unknown. The aim of this study was to compare the effects of a loading dose of dexmedetomidine combined with propofol or sevoflurane on hemodynamics during anesthesia maintenance.MethodsEighty-four patients who were scheduled for general surgery under balanced general anesthesia were randomly allocated into 4 groups (n = 21): the propofol and dexmedetomidine group, the sevoflurane and dexmedetomidine group, the propofol and normal saline group, or the sevoflurane and normal saline group. The hemodynamic indexes at the time of just before, 5 min after and the end of study drug infusion (dexmedetomidine or normal saline) were recorded. The incidence rates of increasing blood pressure at the end of study drug infusion (greater than 20% compared to baseline or before study drug infusion) were evaluated.ResultsMean arterial pressure increased significantly (P < 0.01) only in the propofol and dexmedetomidine group after intravenous dexmedetomidine compared administration. 80% of cases with propofol and dexmedetomidine had increased mean arterial blood pressure compared to only 5% of cases in the sevoflurane and dexmedetomidine group (P < 0.05). Heart rates in the propofol and dexmedetomidine and the sevoflurane and dexmedetomidine groups decreased significantly after dexmedetomidine infusion (P < 0.01).ConclusionsIntraoperative administration of a loading dose of dexmedetomidine combined with propofol in anesthesia maintenance proceeded a significant increase in blood pressure. In contrast, it combines with sevoflurane didn’t produce increased blood pressure. Meanwhile it is not unexpected that dexmedetomidine combined with propofol or sevofurance decreased heart rate, due to the known side effects of DEX. Therefore, dexmedetomidine should be used cautiously during the entire intravenous anesthesia maintenance period, especially during maintenance with propofol.Trial registrationChinese Clinical Trial Registry, ChiCTR-IOR-17010423, registered on 13 January 2017.

EFFECT OF MELATONIN ON HYPERTENSION AND DIABETES INDUCED EXPERIMENTALLY IN ADULT MALE ALBINO RATS

Background: Diabetes Mellitus is the most common endocrine disorder. It is a pathological state leads to long term complications causing damage of different tissue and organs as heart and blood vessels. Hypertension is one of the leading causes of mortality and morbidity. Melatonin has extraordinary antioxidant potential and reduce the level of free radical burden on the level of both oxygen and nitrogen species. Objective: Evaluation of melatonin on hypertension and diabetes induced experimentally in adult male albino rats. Materials and Methods: Seventy adult male albino rats of local strain were divided into equal seven groups as follow: Group I: served as control group received normal saline, Group II: diabetic group, Group III: hypertensive group, Group IV: Diabetic-hypertensive group, Group V: diabetic-melatonin-treated group, Group VI: Hypertensive-melatonin-treated group and Group VII: Diabetic-hypertensive-melatonin-treated group. At the end of experimental period, blood samples were obtained for detwrmination of glycated hemoglobin, plasma glucose, serum lipid profile (total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride (TG)), serum insulin, serum urea and serum creatinine levels. Measurments of blood pressure were performed for the hypertensive rats. Also, cardiac muscles samples were obtained for histopathology study. Results: STZ led to significant increase in blood glucose, glycated hemoglobin, cholesterol, TG, LDL, serum urea and serum creatinine levels associated with significant decrease in serum insulin level.Cadmium led to significant increase in total cholesterol, TG, LDL, serum urea and serum creatinine levels associated with significant increase in blood pressure. Melatonin treatment led to significant decrease of blood glucose, glycated hemoglobin, total cholesterol, TG, LDL, serum urea and serum creatinine levels associated with significant increase in serum insulin level associated with significant decrease blood pressure. Conclusion: Melatonin has a protective effect against cardiac muscle abnormalities in diabetic, diabetic-hypertensive and hypertensive rats due to its antioxidant properties.

Dysautonomia in heavy drinkers for more than 5 years of alcoholic consumption with intact liver function

Background: It is known for long that alcoholic liver cirrhosis is characterized by autonomic dysfunction due to the underlying liver pathology. However, alcohol can have a direct effect on the autonomic functions even before the liver functions are altered. Aims and Objectives: We have undertaken this study to test and compare the autonomic function status in apparently healthy alcoholics with normal liver function tests with age- and sex-matched healthy individuals. Materials and Methods: Thirty healthy non-alcoholics with normal liver function as controls and 30 apparently healthy alcoholics for more than 5 years with normal liver function tests were taken for this study. Autonomic function tests for both parasympathetic and sympathetic functions were performed in both these groups, and the results were compared. Result: Parasympathetic function tests were within the normal range except for the resting heart rate (HR) which showed a significant increase (P < 0.01) in the study subjects compared with the controls. Sympathetic tests showed a very significant increase in blood pressure (BP) response to postural change and a significant change in handgrip test. Conclusion: Resting HR and BP response to postural change were increased and BP response to handgrip test has shown a significant change in study subjects compared to controls which suggest that both sympathetic and parasympathetic functions are altered in them. We will conclude this study with the findings that alcohol has a direct effect on the autonomic nervous system even without any liver function tests alteration.

EFFECT OF MELATONIN ON HYPERTENSION AND DIABETES INDUCED EXPERIMENTALLY IN ADULT MALE ALBINO RATS

Background: Diabetes Mellitus is the most common endocrine disorder. It is a pathological state leads to long term complications causing damage of different tissue and organs as heart and blood vessels. Hypertension is one of the leading causes of mortality and morbidity. Melatonin has extraordinary antioxidant potential and reduce the level of free radical burden on the level of both oxygen and nitrogen species. Objective: Evaluation of melatonin on hypertension and diabetes induced experimentally in adult male albino rats. Materials and Methods: Seventy adult male albino rats of local strain were divided into equal seven groups as follow: Group I: served as control group received normal saline, Group II: diabetic group, Group III: hypertensive group, Group IV: Diabetic-hypertensive group, Group V: diabetic-melatonin-treated group, Group VI: Hypertensive-melatonin-treated group and Group VII: Diabetic-hypertensive-melatonin-treated group. At the end of experimental period, blood samples were obtained for detwrmination of glycated hemoglobin, plasma glucose, serum lipid profile (total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride (TG)), serum insulin, serum urea and serum creatinine levels. Measurments of blood pressure were performed for the hypertensive rats. Also, cardiac muscles samples were obtained for histopathology study. Results: STZ led to significant increase in blood glucose, glycated hemoglobin, cholesterol, TG, LDL, serum urea and serum creatinine levels associated with significant decrease in serum insulin level.Cadmium led to significant increase in total cholesterol, TG, LDL, serum urea and serum creatinine levels associated with significant increase in blood pressure. Melatonin treatment led to significant decrease of blood glucose, glycated hemoglobin, total cholesterol, TG, LDL, serum urea and serum creatinine levels associated with significant increase in serum insulin level associated with significant decrease blood pressure. Conclusion: Melatonin has a protective effect against cardiac muscle abnormalities in diabetic, diabetic-hypertensive and hypertensive rats due to its antioxidant properties.

Renal sympathetic denervation lowers arterial pressure in canines with obesity-induced hypertension by regulating GAD65 and AT1R expression in rostral ventrolateral medulla

ABSTRACTTo explore the roles of glutamate acid decarboxylase 65 (GAD65) and angiotensin II type 1 receptor (AT1R) in the action of renal sympathetic denervation (RSD) on obesity-induced hypertension in canines. Thirty-two beagles were randomly divided into a hypertensive model (n = 22) and control (n = 10) groups. A hypertensive canine model was established by feeding a high-fat diet. Twenty hypertensive beagles were randomized equally to a sham-surgery and RSD-treated group receiving catheter-based radiofrequency RSD. Compared with the control group, the sham-surgery group exhibited significant increases in blood pressure, serum angiotensin II level, rostral ventrolateral medulla (RVLM) glutamate level, and AT1R mRNA and protein expression and decreases in γ-amino acid butyric acid (γ-GABA) level and GAD65 mRNA and protein expression in the RVLM (all P < 0.05). Treatment with RSD significantly attenuated the above abnormal alterations (all P < 0.05). Linear correlation analysis revealed that angiotensin II level was positively correlated with glutamate level (r = 0.804) and inversely correlated with γ-GABA level (r = −0.765). GAD65 protein expression was positively correlated with γ-GABA level (r = 0.782). Catheter-based radiofrequency RSD can decrease blood pressure in obesity-induced hypertensive canines. The antihypertensive mechanism might be linked to upregulation of GAD65 and downregulation of AT1R in the RVLM.

Combined Dextroamphetamine and Transcranial Direct Current Stimulation in Poststroke Aphasia.

There is a growing need for various effective adjunctive treatment options for speech recovery after stroke. A pharmacological agent combined with noninvasive brain stimulation has not been previously reported for poststroke aphasia recovery. In this "proof of concept" study, we aimed to test the safety of a combined intervention consisting of dextroamphetamine, transcranial direct current stimulation, and speech and language therapy in subjects with nonfluent aphasia. Ten subjects with chronic nonfluent aphasia underwent two experiments where they received dextroamphetamine or placebo along with transcranial direct current stimulation and speech and language therapy on two separate days. The Western Aphasia Battery-Revised was used to monitor changes in speech performance. No serious adverse events were observed. There was no significant increase in blood pressure with amphetamine or deterioration in speech and language performance. Western Aphasia Battery-Revised aphasia quotient and language quotient showed a statistically significant increase in the active experiment. Comparison of proportional changes of aphasia quotient and language quotient in active experiment with those in placebo experiment showed significant difference. We showed that the triple combination therapy is safe and implementable and seems to induce positive changes in speech and language performance in the patients with chronic nonfluent aphasia due to stroke.

PP.16.34] EFFECT OF SELF-MEASUREMENT OF BLOOD PRESSURE ON HEMODYNAMICS – THE ANSIA STUDY

Objective: Blood pressure (BP) variability and anxiety responses may influence BP measurement. We recently showed that ∼20% of patients referred for out-of-office BP measurement have a significantly higher home compared to ambulatory BP and, in addition, a large difference between office and ambulatory BP indicative of a white coat effect. We hypothesized that these patients may have an anxiety response upon the self-measurement of BP or ‘auto-cuff’ response. The objective of the study was to evaluate BP responses during self-BP measurement. Design and method: We included 50 subjects, 25 (mean age 66.3±10.9 years, 37.5% female) with and 25 (mean age 57.6 ± 10.2 years, 48.0% female) without a previously established difference between home and ambulatory BP = >10/5 mmHg. All subjects performed 10 consecutive measurements after at least 10 minutes rest followed by another resting period of 10 minutes, while receiving continuous non-invasive monitoring of BP and central hemodynamics. At the end of the self-measurements recording was continued to complete the 30-minute period. Mean BP of the 60 seconds before the start of the self-measurements was used as baseline and compared with the first 10 seconds after the beginning of each self-measurement. Results: observed a significant increase in BP during self-measurement compared to baseline, which was greater in subjects with a large difference between home and ambulatory BP (135.0 ± 23.6/74.1 ± 14.2 vs 141.0 ± 26.1/78.2 ± 12.7 mmHg, p < 0.001) compared to those without (134.5 ± 20.3/77.4 ± 10.9 vs 138.9 ± 25.0/80.0 ± 12.7 mmHg, p = 0.028/0.019).The increase in BP was accompanied by an increase in cardiac output (5.2 ± 1.5 vs 5.4 ± 1.5 lpm, p = 0.018 and 5.4 ± 1.5 vs 5.6 ± 1.5 lpm, p = 0.019, respectively) and heart rate (67.0 ± 14.5 vs 71.0 ± 14.9 bpm, p = 0.005 and 71.0 ± 13.2 vs 74.3 ± 13.4 bpm, p < 0.001). No attenuation could be observed in BP responses between the first three and the last three self-measurements. Conclusions: Our results support the existence of an ‘auto-cuff’ response during self-BP measurement. BP responses did not attenuate during repeated measurements. In addition, anticipation of self-BP measurement appears to contribute to the increase in BP.

Abstract 046: Chronic Estrogen Replacement Prevents the Increase in Blood Pressure in Female IUGR Offspring at 12 Months of Age

Low birth weight (LBW ) is associated with an earlier age at menopause and a greater prevalence of hypertension in women in later life. Using a rodent model of LBW induced by placental insufficiency, previous studies from our lab indicate that intrauterine growth restriction ( IUGR ) programs a significant increase in blood pressure ( BP ) by 12 months of age in female IUGR offspring. Female IUGR are also acyclic by 12 months of age, or 6 months prior to control indicative of early reproductive senescence. The mechanisms involved in menopause related cardiovascular risk are not clear. Furthermore, the link between birth weight and the greater prevalence for hypertension in LBW women in later life is not known. Female IUGR exhibit a shift in the testosterone to estradiol ratio at 12 months of age. Thus, this study tested the hypothesis that a loss of estradiol ( E2 ) contributes to the increase in BP in female IUGR offspring that develops by 12 months of age. Female rats received vehicle or 17β-Estradiol valerate minipellets (1.5mg for 60-day release) for 6 weeks starting at 12 months of age with BP measured in conscious, chronically catheterized rats following treatment (2way ANOVA; Tukey’s multiple comparison). BP was significantly increased in vehicle-treated IUGR relative to vehicle-treated Control (*, p&lt;0.05); an increase that was abolished by chronic E2 in IUGR (**, p&lt;0.05). Uterine weight, a crude marker of E2, was significantly increased by chronic E2 in both Control and IUGR E2-treated offspring (**, p&lt;0.05). Therefore, this study indicates that E2 withdrawal after early reproductive senescence contributes to the increase in BP that develops in later life in female IUGR offspring.

Selective Nrf2 Gene Deletion in the Rostral Ventrolateral Medulla Evokes Hypertension and Sympathoexcitation in Mice.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master transcriptional regulator of redox homeostasis that impacts antioxidant gene expression. Central oxidative stress and reduced antioxidant enzyme expression in the rostral ventrolateral medulla (RVLM) contributed to sympathoexcitation in chronic heart failure. In the current study, we hypothesized that deletion of Nrf2 in the RVLM would increase sympathetic drive and blood pressure. Experiments were performed in Nrf2-floxed mice treated with microinjection of lentiviral-Cre-GFP or lentiviral-GFP into the RVLM. Two weeks after viral administration, Nrf2 message, protein, oxidative stress, cardiovascular function, and sympathetic outflow were evaluated. We found that (1) Nrf2 mRNA and protein in the RVLM were significantly lower in Cre mice compared with control GFP mice. Nrf2-targeted antioxidant enzymes were downregulated, whereas reactive oxygen species were elevated. (2) Blood pressure measurements indicated that Cre mice displayed a significant increase in blood pressure (mean arterial pressure, 123.7±3.8 versus 100.2±2.2 mm Hg; P<0.05, n=6), elevated urinary norepinephrine (NE) concentration (456.4±16.9 versus 356.5±19.9 ng/mL; P<0.05, n=6), and decreased spontaneous baroreflex gain (up sequences, 1.66±0.17 versus 3.61±0.22 ms/mm Hg; P<0.05, n=6; down sequences, 1.89±0.12 versus 2.98±0.19 ms/mm Hg; P<0.05, n=6). (3) Cre mice displayed elevated baseline renal sympathetic nerve activity and impaired inducible baroreflex function. These data suggest that Nrf2 gene deletion in the RVLM elevates blood pressure, increases sympathetic outflow, and impairs baroreflex function potentially by impaired antioxidant enzyme expression.

Effect of vitamin K1 supplementation on matrix Gla protein level and vascular calcification in hemodialysis patients

BackgroundMatrix Gla protein (MGP) is a potent calcification inhibitor of the arterial wall. Its activity depends on vitamin K-dependent γ-carboxyglutamate.AimWe aimed to investigate the effect of vitamin K1 on MGP levels after 3 months’ supplementation and the relationship between MGP level and vascular calcification.Patients and methodsA prospective case–control pilot study was conducted overa period of 3 months. The study included 57 long-term hemodialysis patients in stable conditions who were divided into two groups and were compared with 27 healthy age-matched controls. Group I consisted of 28 hemodialysis patients who received vitamin K1 at10 mg three times per week for a successive period of 3 months. Group II consisted of 29 hemodialysis patients who did not receive vitamin K. Group III consisted of 27 healthy participants as controls. The serum level of MGP was measured by radioimmunoassay; in addition, hemoglobin%, parathyroid hormone, calcium, phosphorus, sodium, potassium, alkaline phosphatase, total cholesterol, triglyceride, and carotid intima–media thickness were also measured. Plain radiograph of the abdomen in lateral view was acquired to determine the abdominal aortic calcification score at the start of the study, which was reassessed after 3 months in groups I and II.ResultsWe found a significant increase in blood pressure, body mass index (BMI) with elevation in the serum level of MGP in patient groups than control from the start. A significant elevation in MGP level was observed in group I accompanied by a decrease in serum cholesterol level, compared with group II. We did not find any significant change in carotid intima–media thickness or abdominal aortic calcification score in either group after 3 months. There was no significant correlation between elevated MGP level and vascular calcification either. No significant difference was found in other parameters.ConclusionVitamin K supplementation may be essential for End Stage Kidney Disease (ESKD) patients on hemodialysis. Vitamin K can increase the level of MGP and decrease cholesterol level, but its beneficial effect on the vascular bed needs a long-term study.

The effects of pollen, propolis, and caffeic acid phenethyl ester on tyrosine hydroxylase activity and total RNA levels in hypertensive rats caused by nitric oxide synthase inhibition: experimental, docking and molecular dynamic studies

The objective of the present study was to evaluate the effects of propolis, pollen, and caffeic acid phenethyl ester (CAPE) on tyrosine hydroxylase (TH) activity and total RNA levels of Nω-nitro-L-arginine methyl ester (L-NAME) inhibition of nitric oxide synthase in the heart, adrenal medulla, and hypothalamus of hypertensive male Sprague dawley rats. The TH activity in the adrenal medulla, heart, and hypothalamus of the rats was significantly increased in the L-NAME group vs. control (p < 0.05). Treatment with L-NAME led to a significant increase in blood pressure (BP) in the L-NAME group compared to control (p < 0.05). These data suggest that propolis, pollen, and CAPE may mediate diminished TH activity in the heart, adrenal medulla, and hypothalamus in hypertensive rats. The decreased TH activity may be due to the modulation and synthesis of catecholamines and BP effects. In addition, the binding mechanism of CAPE within the catalytic domain of TH was investigated by means of molecular modeling approaches. These data suggest that the amino acid residues, Glu429 and Ser354 of TH may play a pivotal role in the stabilization of CAPE within the active site as evaluated by molecular dynamics (MD) simulations. Gibbs binding free energy (ΔGbinding) of CAPE in complex with TH was also determined by post-processing MD analysis approaches (i.e. Poisson-Boltzmann Surface Area (MM-PBSA) method).