Effects of intracerebroventricularly injected glucagon-like peptide-1 on cardiovascular parameters; role of central cholinergic system and vasopressin.

Isbil-Buyukcoskun N, Gulec G.

Uludag University Medical Faculty, Department of Physiology, 16059, Gorukle, Bursa, Turkey. nisibil uludag.edu.tr

We aimed to investigate the effects of intracerebroventricularly (i.c.v.) injected glucagon-like peptide-1 (GLP-1) on blood pressure and heart rate, and whether central cholinergic system and vasopressinergic system play roles in these effects. Male Wistar albino rats were used throughout the experiments. Blood pressures and heart rates were observed before and for 30 min following drug injections. i.c.v. GLP-1 (100, 500 and 1000 ng/10 microl) caused a dose-dependent increase in both blood pressure and heart rate. Nicotinic receptor antagonist mecamylamine (25 microg/10 microl, i.c.v.) and muscarinic receptor antagonist atropine (5 microg/10 microl, i.c.v.) prevented the stimulating effect of GLP-1 on blood pressure. The effect of GLP-1 on heart rate was blocked only by mecamylamine. The V1 receptor antagonist of vasopressin (B-mercapto B, B-cyclopentamethylenepropionyl, O-Me-Tyr,Arg)-vasopressin (10 microg/kg), that was applied intraarterially, only prevented the effect of GLP-1 on blood pressure, but did not show any effect on heart rate. Our data indicate that i.c.v. GLP-1 increases blood pressure and heart rate, and stimulation of central nicotinic and partially muscarinic receptors and vasopressinergic system play a role in the effects of i.c.v. GLP-1 on blood pressure. The effect of GLP-1 on heart rate may be partially due to stimulation of central nicotinic receptors.

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Maternal age and other predictors of newborn blood pressure.

Gillman MW, Rich-Edwards JW, Rifas-Shiman SL, Lieberman ES, Kleinman KP, Lipshultz SE.

Department of Ambulatory Care and Prevention, Harvard Medical School/Harvard Pilgrim Health Care, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. matthew_gillman hms.harvard.edu

OBJECTIVE: To investigate perinatal predictors of newborn blood pressure. STUDY DESIGN: Among 1059 mothers and their newborn infants participating in Project Viva, a US cohort study of pregnant women and their offspring, we obtained five systolic blood pressure readings on a single occasion in the first few days of life. Using multivariate linear regression models, we examined the extent to which maternal age and other pre- and perinatal factors predicted newborn blood pressure level. RESULTS: Mean (SD) maternal age was 32.0 (5.2) years, and mean (SD) newborn systolic blood pressure was 72.6 (9.0) mm Hg. A multivariate model showed that for each 5-year increase in maternal age, newborn systolic blood pressure was 0.8 mm Hg higher (95% CI, 0.2, 1.4). In addition to maternal age, independent predictors of newborn blood pressure included maternal third trimester blood pressure (0.9 mm Hg [95% CI, 0.2, 1.6] for each increment in maternal blood pressure); infant age at which we measured blood pressure (2.4 mm Hg [95% CI 1.7, 3.0] for each additional day of life); and birth weight (2.9 mm Hg [95% CI, 1.6, 4.2] per kg). CONCLUSIONS: Higher maternal age, maternal blood pressure, and birth weight were associated with higher newborn systolic blood pressure. Whereas blood pressure later in childhood predicts adult hypertension and its consequences, newborn blood pressure may represent different phenomena, such as pre- and perinatal influences on cardiac structure and function.

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Is systolic blood pressure recovery after exercise a predictor of mortality?

Ellis K, Pothier CE, Blackstone EH, Lauer MS.

Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

BACKGROUND: An attenuated systolic blood pressure recovery after exercise has been associated with the severity of atherosclerotic heart disease. METHODS: For 6 years, we observed 12,379 patients who underwent symptom-limited exercise testing. We excluded patients receiving antihypertensive medication and patients with valvular disease, emphysema, end-stage renal disease, heart failure, left ventricular systolic dysfunction, and atrial fibrillation. Blood pressure recovery ratio was defined as the ratio of systolic blood pressure at 3 minutes into recovery to systolic blood pressure at peak exercise; this has been shown to correlate with angiographic severity of coronary disease. RESULTS: The blood pressure recovery ratios ranged from 0.36 to 1.62, with values for increasing quartiles of 0.72 +/- 0.05, 0.82 +/- 0.02, 0.88 +/- 0.02, and 0.99 +/- 0.07. During follow-up, there were 430 deaths (3%). Five-year Kaplan Meier survival rates were 0.975, 0.974, 0.969, and 0.966 in quartiles 1 to 4, respectively. Compared with patients in the lowest quartile of blood pressure recovery ratio, patients in the highest quartile were at somewhat increased risk (hazard ratio, 1.71; 95% CI, 1.31-2.24; P <.001). However, after adjusting for age, sex, body mass index, resting heart rate and blood pressure, peak systolic blood pressure, heart rate recovery, exercise chronotropic response, cardiac history, and standard risk factors, this association was no longer present (adjusted hazard ratio, 1.05; 95% CI, 0.8-1.38; P =.74). CONCLUSIONS: In this low-risk population, abnormal systolic blood pressure recovery after exercise was not independently predictive of mortality after correcting for differences in baseline and exercise characteristics.

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Ethnic, geographic and dietary influences upon vasoactive hormones and blood pressure among Greenland Inuit and Danes.

Jorgensen ME, Pedersen MB, Siggaard C, Sorensen TB, Mulvad G, Hansen JC, Skjoldborg H, Pedersen EB.

Department of Medicine, Queen Ingrid's Hospital, Nuuk, Denmark. maej steno.dk

AIM: To study levels of vasoactive hormones and urinary excretion of sodium and potassium between groups of Greenland Inuit and Danes, and to analyse the relationship between these hormones and 24-h blood pressure, including nightly blood pressure dips and pulse pressure. METHODS: 145 Greenlandic participants were categorized in three groups according to degree of westernization, based on dietary habits and current place of residence; 41 Danes were included as controls. Twenty-four-hour blood pressure was measured. Venous plasma concentrations of vasoactive hormones were measured. Urine was collected for 24 hours for analysis of excretion of sodium and potassium. RESULTS: The Inuit population of Greenland had a lower diastolic blood pressure, a higher pulse pressure and lower nocturnal blood pressure dip than Danes had. Angiotensin II in plasma and urine excretion of potassium were higher among Greenlanders compared with Danes, irrespective of diet and place of residence. Aldosterone and urine excretion of sodium were significantly higher among participants in Denmark compared with participants in Greenland. Brain natriuretic peptide and atrial natriuretic peptide were independently and negatively associated with diastolic blood pressure, and vasopressin was positively associated with systolic blood pressure and pulse pressure. Ethnic differences in the effect of vasoactive hormones or urinary sodium and potassium excretion could not explain the difference in blood pressure. CONCLUSION: It is suggested that a high dietary intake of potassium and low sodium intake among Greenlanders may affect blood pressure. Further attention should be drawn to the occurrence of high pulse pressure and high activity in the renin-angiotensin system in Inuit populations.

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Exercise blood pressure is related to insulin resistance in subjects with two hypertensive parents.

Andersen UB, Olsen MH, Dige-Petersen H, Ibsen H.

Department of Clinical Physiology and Nuclear Medicine, Glostrup Hospital, Denmark. uandersen dadlnet.dk

INTRODUCTION: Insulin resistance has been implicated in the pathogenesis of essential hypertension. Elevated blood pressure during physical exercise is a more powerful predictor of future hypertension than resting blood pressure. We have therefore studied the relationship between insulin resistance and blood pressure response to exercise in strongly hypertension-prone subjects. MATERIAL: Twenty-five normotensive subjects aged 18-35 years with bi-parental hypertension, and 26 matched controls with normotensive parents. METHODS: (i) Maximal exercise tolerance test with continuous gas-exchange measurement; (ii) blood pressure at rest, during exercise and 24-h ambulatory; (iii) euglycemic hyperinsulinemic clamp. RESULTS: Diastolic blood pressure during exercise was higher in hypertensionprone subjects as compared to controls, but only in subjects with low insulin sensitivity. Resting and 24-h diastolic blood pressure were higher in hypertension-prone subjects, but independent of insulin sensitivity level. Insulin sensitivity and exercise capacity were similar in the groups. CONCLUSION: Diastolic blood pressure during exercise was higher in hypertension-prone subjects as compared to controls, but only in insulin-resistant subjects. Since elevated blood pressure during physical exertion is a predictor of future hypertension, these findings may suggest that insulin resistance is involved in the pathogenesis of essential hypertension.

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Review of clinical outcomes in nocturnal haemodialysis patients after renal transplantation.

McCormick BB, Pierratos A, Fenton S, Jain V, Zaltzman J, Chan CT.

Division of Nephrology, Toronto General Hospital, University of Toronto, Ontario, Canada.

BACKGROUND: Nocturnal haemodialysis (NHD) is a novel form of haemodialysis therapy that is associated with improved blood pressure control when compared to conventional haemodialysis (CHD). Current studies suggest that NHD lowers blood pressure through a decrease in peripheral resistance. The graft and blood pressure outcomes of NHD patients who undergo renal transplantation are unknown. METHODS: We reviewed the renal allograft and blood pressure outcomes of 15 NHD patients who underwent renal transplantation. An age and vintage matched cohort of 29 CHD patients was used as controls. RESULTS: The rate of delayed graft function (DGF) tended to be higher in the NHD group compared to the CHD group (64 vs 41%, P = 0.15), however the 1-year graft function (53+/-6 vs 59+/-5 ml/min, P = 0.426) and graft survival (92 vs 95%, P = 0.751) were similar. Intra-operatively, NHD patients had lower minimum systolic (92+/-5 vs 109+/-4, P = 0.03) and diastolic (48+/-3 vs 64+/-2, P = 0.02) blood pressures in comparison to the CHD cohort. Pathologically, acute tubular necrosis accounted for 100% of DGF in the NHD group in contrast to 75% in the CHD population (P = 0.01). Pre-transplant mean systolic BP (sBP) was significantly lower in the NHD group compared to the CHD group (113+/-6 vs 145+/-10 mmHg, P<0.001). At 12 months post-transplant, mean sBP increased from baseline in the NHD group ( triangle up sBP 22+/-7 mmHg, P = 0.009) while in the CHD group mean sBP fell (Delta sBP -14+/-5 mmHg, P = 0.014). Mean arterial and diastolic BP exhibited similar changes. These trends persisted after 24 months of post-transplant follow-up. CONCLUSIONS: One-year graft outcomes and blood pressures are similar for NHD and CHD patients who undergo renal transplantation. Unlike CHD patients, NHD patients experienced a significant fall in their intra-operative blood pressures, which likely contributed towards the delayed graft function in this cohort of patients. Further prospective studies are needed to examine the underlying differences in haemodynamics and long-term graft survival between the two renal replacement modalities.

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Integration of autonomic and local mechanisms in regulating cardiovascular responses to heating and cooling in a reptile (Crocodylus porosus).

Seebacher F, Franklin CE.

Integrative Physiology, School of Biological Sciences A08, The University of Sydney, 2006 Sydney, NSW, Australia. fseebach bio.usyd.edu.au

Reptiles change heart rate and blood flow patterns in response to heating and cooling, thereby decreasing the behavioural cost of thermoregulation. We tested the hypothesis that locally produced vasoactive substances, nitric oxide and prostaglandins, mediate the cardiovascular response of reptiles to heat. Heart rate and blood pressure were measured in eight crocodiles (Crocodylus porosus) during heating and cooling and while sequentially inhibiting nitric-oxide synthase and cyclooxygenase enzymes. Heart rate and blood pressure were significantly higher during heating than during cooling in all treatments. Power spectral density of heart rate and blood pressure increased significantly during heating and cooling compared to the preceding period of thermal equilibrium. Spectral density of heart rate in the high frequency band (0.19-0.70 Hz) was significantly greater during cooling in the saline treatment compared to when nitric-oxide synthase and cyclooxygenase enzymes were inhibited. Cross spectral analysis showed that changes in blood pressure preceded heart rate changes at low frequencies (< 0.1 Hz) only. We conclude that the autonomic nervous system controls heart rate independently from blood pressure at higher frequencies while blood pressure changes determine heart rate at lower frequencies. Nitric oxide and prostaglandins do not control the characteristic heart rate hysteresis response to heat in C. porosus, although nitric oxide was important in buffering blood pressure against changes in heart rate during cooling, and inhibition caused a compensatory decrease in parasympathetic stimulation of the heart.

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Blood pressure measures and electrocardiogram-defined myocardial infarction in an Iranian population: Tehran Lipid and Glucose study.

Ghanbarian A, Rashidi A, Madjid M, Azizi F.

Endocrine and Metabolism Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran. Azizi erc-iran.com

The purpose of this study was to describe blood pressure values in Iranian adults with electrocardiogram (ECG) evidence of a myocardial infarction (MI). High blood pressure is a risk factor, and an ECG can be diagnostic of coronary artery disease. In recent studies the role of pulse pressure in predicting coronary artery disease has been suggested to be more important than that of blood pressure. From among participants of the Tehran Lipid and Glucose study, data for 2479 men and 3060 women aged > or =30 years not currently using any antihypertensive medication were collected. The study used the mean of two separate blood pressure measurements for each individual. ECG findings of all subjects were coded according to Minnesota ECG coding criteria, and they were categorized into probable/possible MI or no MI. ECG evidence of probable or possible MI was found in 1.2% of subjects (1.8% in men vs. 0.8% in women, p<0.001). Prevalence of ECG-defined MI in hypertensive persons was two-fold higher than in normotensives. Adjusted for age, sex, and body mass index, mean diastolic blood pressure was significantly lower in cases with ECG-defined MI than in subjects without MI (p<0.03). There was a strong positive correlation between pulse pressure and systolic blood pressure in both hypertensive/normotensive and MI/no MI groups at the p<0.001 level. There was a weak inverse correlation between diastolic blood pressure and pulse pressure in hypertensive/normotensive/no MI groups (-0.32 and -0.14, both p<0.001). Diastolic blood pressure was not correlated with pulse pressure in cases with MI. Prevalence of ECG-defined MI in hypertensive cases was higher than in normotensives. Systolic blood pressure is a better predictor for pulse pressure than diastolic blood pressure in both normotensive and hypertensive populations with or without ECG-defined MI.

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