Oxygen dependence of tyrosine hydroxylase.

The effects of dioxygen on tyrosine hydroxylase (TH) activity was studied, measuring the formation of DOPA from tyrosine, (3)H(2)O from 3,5-(3)H-tyrosine, or by direct oxygraphic determination of oxygen consumption. A high enzyme activity was observed during the initial 1-2 min of the reactions, followed by a decline in activity, possibly related to a turnover dependent substoichiometrical oxidation of enzyme bound Fe(II) to the inactive Fe(III) state. During the initial reaction phase, apparent K (m)-values of 29-45 microM for dioxygen were determined for all human TH isoforms, i.e. 2-40 times higher than previously reported for TH isolated from animal tissues. After 8 min incubation, the K (m) (O(2))-values had declined to an average of 20 +/- 4 microM. Thus, TH activity may be severely limited by oxygen availability even at moderate hypoxic conditions, and the enzyme is rapidly and turnover dependent inactivated at the experimental conditions commonly employed to measure in vitro activities.

Predictors of new-onset diabetes mellitus in hypertensive patients: the VALUE trial.

Diabetes mellitus often develops in patients with hypertension. We investigated predictors of diabetes mellitus development in hypertensives at risk of developing the disease in the VALUE trial population. Among the 9995 non-diabetic hypertensive patients at baseline, 1298 patients developed diabetes mellitus during the average follow-up of 4.2 years. New-onset diabetes mellitus was defined from adverse event reports, information about new antidiabetic medication and/or a fasting glucose >or=7.0 mmol l(-1) at the end of trial. Twenty-five potential baseline predictors of new-onset diabetes mellitus were analysed by univariate logistic regression and 14 of 25 predictors were found to be statistically significant with a P-value <0.05. The predictors were in order of decreasing significance; glucose, body mass index (BMI), age, uric acid, non-Caucasian race, haemoglobin, heart rate, randomized study treatment, history of coronary heart disease (CHD), gender, total cholesterol, proteinuria, potassium and creatinine. Multivariate stepwise logistic regression analyses were used and potential baseline predictors of new-onset diabetes mellitus were considered significant by four different models (P-value <0.001). The final multivariate model selected included all patients, but not treatment group as a potential predictor, and the six significant predictors identified from this model were glucose, BMI, non-Caucasian race, age, heart rate and history of CHD. In conclusion, glucose and BMI were the most important predictors of new-onset diabetes mellitus in hypertensive patients at high cardiovascular risk, and easily accessible clinical characteristics strongly predict patients at risk of developing diabetes mellitus.

Cardiovascular reactivity, coronary risk factors, and sympathetic activity in young men.

We have previously demonstrated that awareness of high blood pressure may increase blood pressure, plasma catecholamine levels, and stress responses. In the present study, three groups of 19-year-old men, all unaware of their blood pressure status, were selected from the first (group-1, 62 +/- 2 mm Hg, [mean +/- SEM], n = 15), 50th (group-50, 90 +/- 4 mm Hg, n = 15), and 99th (group-99, 123 +/- 5 mm Hg, n = 14) percentiles in causal mean blood pressure at a screening. They were studied (blinded examiners) with intra-arterial blood pressure recordings and multiple measurements of arterial plasma epinephrine and norepinephrine during a mental arithmetic challenge and cold pressor test. Despite high mean blood pressure at the screening, group-99 did not differ from group-50 either in intra-arterial mean blood pressure after 30 minutes of supine rest (89 +/- 3 versus 86 +/- 2 mm Hg) or in serum lipids and resting plasma epinephrine and norepinephrine. However, in group-99 resting plasma epinephrine showed a positive hyperbolic relation to resting diastolic blood pressure (r = .73, P = .004) and a negative hyperbolic relation to the ratio of high-density lipoprotein cholesterol to total cholesterol (r = -.75, P = .002). None of these correlations were present in the two other groups. Furthermore, the three groups differed in heart rate responses (P < .0005) and systolic (P < .0005) and diastolic (P < .05) blood pressure responses to mental arithmetic challenge, group-99 being hyperreactive compared with the other two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin sensitivity is related to physical fitness and exercise blood pressure to structural vascular properties in young men.

Insulin resistance is related to physical inactivity, which is a risk factor for cardiovascular disease and death. Moreover, blood pressure responses during the first 6 minutes of an exercise test (600 kilo/pound/meter [kpm] per min) are more predictive for cardiovascular morbidity and mortality than blood pressure at rest, which could reflect that exercise blood pressure correlates more closely to peripheral structural vascular changes than casual blood pressure. We have recently shown a correlation between insulin resistance and minimal forearm vascular resistance (MFVR) in young men recruited from the highest blood pressure percentiles during a military draft session. In the present study, we tested the hypotheses that insulin sensitivity relates to physical fitness and that blood pressure responses during an exercise test relate to peripheral structural vascular changes in these men; we also tested whether these findings were interrelated. We assessed insulin sensitivity and physical fitness in 27 young men randomly selected from the cohort having a blood pressure of 140/90 mm Hg or higher during the compulsory military draft session in Oslo. Insulin sensitivity correlated with physical fitness (r=0.58, P=0.002). Systolic blood pressure after 6 minutes of exercise (600 kpm/min) correlated with MFVR (r=0.46, P=0.015). MFVR and physical fitness independently explained 60% of the variation in insulin sensitivity, and MFVR independently explained 19% of the variation of systolic blood pressure after 6 minutes of exercise. In conclusion, insulin sensitivity is related to physical fitness and exercise blood pressure to structural vascular properties in these young men.

Relationship between insulin sensitivity and maximal forearm blood flow in young men.

Insulin resistance is a part of the metabolic cardiovascular syndrome. We aimed to test the hemodynamic hypothesis of insulin resistance, which suggests that a decreased skeletal muscle blood supply with subsequent reduced nutritional flow causes insulin resistance in skeletal muscle. We assessed determinants of peripheral blood flow such as maximal forearm blood flow (MFBF), minimal forearm vascular resistance (MFVR), and whole blood viscosity (WBV) in 27 young men with borderline elevation of blood pressure. Insulin sensitivity measured as glucose disposal rate (GDR) correlated with MFBF (r=0.55, P=0.003), MFVR (r=-0.58, P=0. 002), and WBV (r=-0.39, P=0.046 at shear rate 201 s-1). There was no correlation between GDR and myocardial thickness or left ventricular mass. In a stepwise multiple regression analysis, MFVR and WBV explained 54% of the variation in GDR. The relative increase in mean arterial blood pressure during a mental stress test, as a marker of reactivity or an alert reaction, was correlated with MFVR (r=0.56, P=0.002) and inversely with GDR (r=-0.45, P=0.018) and MFBF (r=-0.49, P=0.01) but not with cardiac dimensions. In a stepwise multiple regression analysis, 48% of the increase in blood pressure during a mental stress test was explained by MFVR and WBV. Fasting insulin correlated with MFVR (r=0.41, P=0.036) and GDR (r=-0.62, P=0.001). These data show a positive association between the appearance of peripheral structural vascular changes as quantified through a hemodynamic technique and insulin resistance in young men with borderline elevation of blood pressure. The cause-effect relationship of this finding needs further evaluations.

Left ventricular mass and cardiovascular reactivity in young men.

The relation between left ventricular wall thickness and mass, arterial plasma catecholamines, and blood pressure at rest and during a mental arithmetic challenge and a cold pressor test was examined in 69 healthy men 19 years of age. The subjects were recruited from the 1st (n = 21), 50th (n = 26), and 99th (n = 22) percentiles in mean blood pressure. All underwent echocardiography to determine mean wall thickness and left ventricular mass. Continuous intra-arterial blood pressure, electrocardiogram, and arterial sampling of plasma catecholamines were performed after 30 minutes of supine rest, during a 5-minute mental arithmetic challenge, and during a 1-minute cold pressor test. Stepwise multiple-regression analyses considering mean wall thickness and left ventricular mass as the dependent variables were applied. Intra-arterial systolic blood pressure (r = .54, P < .0001) and arterial plasma epinephrine (r = .31, P = .009) after 30 minutes of supine rest were the only independent explanatory variables of mean wall thickness (multiple R2 = .33, P < .0001). Blood pressure at screening and during mental stress and cold pressor tests were not independent explanatory variables. The present study suggests that resting arterial blood pressure and plasma epinephrine may be of importance for development of left ventricular hypertrophy.

Awareness of high blood pressure increases arterial plasma catecholamines, platelet noradrenaline and adrenergic responses to mental stress.

Thirty-six, 19-year-old men within the 95th percentile of mean blood pressure (110 mmHg) at a routine medical screening were randomized into two groups and requested to return for a follow-up visit in 2 weeks. One group was sent a neutral letter, while the other was sent a letter conveying the information that their blood pressures were elevated. After 15 min sitting in the laboratory, there was a significantly higher heart rate (P less than 0.05) in the informed group. Thirteen informed and 13 uninformed subjects were examined further by intra-arterial blood pressure recording and serial sampling of arterial catecholamines during cold pressor and mental stress tests. The study was undertaken examiner-blind. Informing the subjects of high blood pressure increased both baseline plasma noradrenaline (P less than 0.01) and adrenaline (P less than 0.05) and intraplatelet noradrenaline (P less than 0.05). Blood pressure (P less than 0.05) and heart rate (P less than 0.05) increased significantly more in the informed group when the subjects were told of the cold pressor test. In addition, there were exaggerated adrenaline (P less than 0.05) and diastolic blood pressure (P less than 0.05) responses to mental stress in the informed group. Thus, awareness of high blood pressure in young men may increase sympathetic tone and responses as measured in the laboratory. Conclusions from studies on early pathogenesis of essential hypertension should therefore be drawn with more caution when patients are aware of their high blood pressure.

Awareness of high blood pressure stimulates platelet release reaction.

The present study aimed at testing the hypothesis of a link between mental stress and blood platelet function. Twenty-nine 19-year-old men were recruited from the 98th percentile of mean blood pressure (116 mmHg) at a routine medical screening. They were not informed about their elevated blood pressures at the time of the screening. One year later they were randomized into two groups. Group 1 (n = 16) was exposed to mental stress by a letter informing them about their high blood pressure, while group 2 (n = 13) was sent a neutral letter. At an examination 2 weeks later, heart rate (p less than 0.05) and plasma adrenaline (p less than 0.05) responses to a cold pressor test were exaggerated in the informed group. The plasma beta-thromboglobulin (beta TG) concentration was elevated in the informed group (p less than 0.05) as was mean blood pressure (p less than 0.05). beta TG correlated positively with hematocrit (r = 0.59, p less than 0.005) and mean blood pressure (r = 0.43, p less than 0.05), and negatively with plasma HDL (r = -0.61, p = 0.001). The study shows that awareness of hypertension induces a hyperadrenergic state which is associated with the platelet release reaction. Under these circumstances platelet release seems to be correlated to established coronary heart disease risk factors.

Blood platelet responses to laboratory stress in young men. The effect of awareness of high blood pressure.

Healthy 19-year old males from the 95th percentile of mean arterial screening blood pressure were randomized to prolonged mental stress by receiving a letter informing of a high screening blood pressure (n = 13), or a neutral letter (n = 13). Blood platelet function in vivo was assessed by measurements of plasma concentrations of the platelet-specific protein beta-thromboglobulin, platelet counts, and mean platelet volumes before and during two laboratory stress tests (hand cold pressor test and arithmetic challenge). The cold pressor test caused a significant increase in beta-thromboglobulin concentrations in both groups, and significantly more in the uniformed group. Platelet count increased significantly in both groups during mental arithmetic with significantly higher counts in the uninformed group. Overall plasma beta-thromboglobulin responses were significantly larger in the uninformed group. This study demonstrates that laboratory stress is associated with blood platelet activation and that awareness of high blood pressure attenuates the platelet responses to such stress tests.

Awareness of hypertension increases blood pressure and sympathetic responses to cold pressor test.

The present study was aimed at examining the effects of awareness of hypertension on blood pressure and sympathetic responses to the cold pressor test. Nineteen-year-old men with similarly elevated mean blood pressure at a medical screening, but without knowledge of this, were randomized into two groups. The first group (n = 16) was sent a letter saying that their pressure was too high, and the second (n = 13) was sent a neutral letter. Information increased mean blood pressure both after 15 min sitting, by an average of 11.5 mm Hg (P less than .01), and after 30 min supine rest, by an average of 4.5 mm Hg (P less than .05). Changes in heart rate (8.4 +/- 2.4 v 1.9 +/- 1.7 beats/min) and plasma epinephrine (0.11 +/- 0.04 v 0.01 +/- 0.03 nmol/L) during execution of a cold pressor test were significantly greater in the informed group (P less than .05). Plasma dopamine was lower in the informed group (P less than .05). Thus, psychological stress caused by the awareness of hypertension may increase blood pressure and sympathetic responses to a provocative maneuver. Ideally, studies on sympathetic function in essential hypertension should be undertaken on subjects unaware of their blood pressure status.

Insulin sensitivity, sympathetic activity, and cardiovascular reactivity in young men.

The present study was undertaken to examine the relationships between insulin sensitivity, blood pressure (BP), and cardiovascular reactivity, and to assess sympathetic nervous system influence. Insulin sensitivity (GDR/I; euglycemic glucose clamp technique) was related to BP and heart rate (HR) in different situations in 40 healthy young men: in the laboratory, during a mental arithmetic stress test, and during baseline conditions at home. GDR/I correlated with supine diastolic BP in the laboratory and with maximum diastolic BP during mental stress (r = -0.46, P = .003; r = -0.62, P = .0001, respectively), but not so strongly with diastolic BP measured at home (r = -0.29, P = .09). Diastolic BP during stress and body mass index were the only independent explanatory variables of GDR/I in multiple regression analysis (multiple R = 0.71, R2 = 0.50, P < .0001). GDR/I and systolic BP were not significantly correlated at any time. GDR/I correlated negatively with HR in the laboratory and with maximum HR during mental stress, but not with HR at home. Maximum plasma epinephrine during stress correlated with stress BP and HR (r = 0.53, P = .001; r = 0.70, P < .0001, respectively) and negatively with GDR/I (r = -0.36, P < .05). In the present study, GDR/I is related to diastolic but not to systolic BP, and more closely correlated to diastolic BP and HR measured during mental stress than to diastolic BP and HR during baseline conditions at home.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of hyperinsulinemia on sympathetic responses to mental stress.

In a recent study, we could not find evidence to support the hypothesis that insulin activates the sympathetic nervous system (SNS) during a hyperinsulinemic glucose clamp procedure. Mental stress tests (MST), however, may be used to detect differences in blood pressure and SNS activity that are not present during baseline or resting conditions. In this study, we aimed to investigate the effects of hyperinsulinemia during glucose clamp on blood pressure and sympathetic responses to mental stress. Borderline hypertensive but otherwise healthy 21-year-old men (n = 18) underwent 5 min of mental arithmetic stress testing (MST-1) before and at the end of 120 min of isoglycemic hyperinsulinemic glucose clamp (MST-2) with infusion rates of glucose and insulin kept constant. Insulin concentration increased from 119 +/- 10 pmol/L to 752 +/- 65 pmol/L. We observed highly significant increases in blood pressure and heart rate in response to MST, but neither insulin nor saline solution infusions affected these responses. During MST-1, norepinephrine increased by 461 +/-165 pmol/L (mean +/- SEM) and epinephrine by 218 +/- 76 pmol/L. During MST-2 the changes were 372 +/- 112 pmol/L and 187 +/- 60 pmol/L, respectively. The norepinephrine (P = .8) and epinephrine (P = .7) responses were unchanged by insulin. Thus, there were similar increases in blood pressure, heart rate, and plasma catecholamine concentrations in arterialized venous blood in response to MST despite the infusion of insulin. A possible time effect was excluded by including a saline solution control group (n = 7) that showed almost identical results. Our results suggest that acute hyperinsulinemia during isoglycemic glucose clamp does not interfere with cardiovascular or sympathetic responses to mental stress.

Biphasic effect of epinephrine on blood glucose during hyperinsulinemia in borderline hypertensive young men.

We aimed to study the glycemic response to epinephrine during hyperinsulinemia and infused epinephrine (0.03 microg/kg/min) for 30 min after 90 min of hyperinsulinemic glucose clamp in 14 borderline hypertensive young men. Plasma epinephrine was increased from 0.34 +/- 0.08 to 2.33 +/- 0.33 nmol/L while insulin and glucose infusions were kept constant with consequent changes in blood glucose. Initially (90 to 95 min), there was a decrease in blood glucose (P = .016) that correlated negatively with glucose disposal rate corrected for insulin (r = -0.55, P = .040) and positively with fasting insulin (r = 0.55). Thereafter, there was an increase in blood glucose (95 to 120 min) (P < .001) that persisted during the recovery period (120 to 140 min). The glucose increase (90 to 140 min) correlated positively with fasting insulin (r = 0.55), systolic blood pressure (r = 0.57), delta epinephrine 90 to 120 min (r = 0.59), and baseline epinephrine (r = 0.57). Blood glucose remained unchanged (P = .207) in a saline control group (n = 6) with a significant group X treatment effect versus epinephrine (P = .003). Thus, epinephrine caused a biphasic response in blood glucose during hyperinsulinemia. The initial dip in glucose was more pronounced with higher insulin sensitivity, corresponding to previous observations during mental stress test. The following increment in blood glucose was positively related to insulin, systolic blood pressure, and epinephrine levels. These data suggest that insulin may modify the glycemic response to epinephrine in a potentially favorable direction and indicate some lag time before epinephrine gains effect. Subjects who are insulin sensitive and have low blood pressure and resting epinephrine levels seem to be less prone to hyperglycemia induced by epinephrine.

The effects of dihydropyridine and phenylalkylamine calcium antagonist classes on autonomic function in hypertension: the VAMPHYRE study.

The aim of the present study was to compare the effects of a long-acting dihydropyridine (amlodipine) and a nondihydropyridine (verapamil) on autonomic function in patients with mild to moderate hypertension. A total of 145 patients with a diastolic blood pressure (BP) between 95 and 110 mm Hg received 8 weeks of verapamil sustained release (240 mg) and amlodipine (5 mg) in a prospective randomized, double blind, cross-over study, both after 4 weeks of placebo. The 24-h autonomic balance was measured by analysis of 24-h heart rate variability and short-term autonomic control of BP by baroreflex sensitivity measurements. Plasma norepinephrine was sampled at rest. Blood pressure was equally reduced from 153/100 mm Hg to 139/91 mm Hg with verapamil and 138/91 mm Hg with amlodipine, P = .50/.59. The low- to high-frequency ratio (LF/HF), reflecting sympathovagal balance, was higher with amlodipine than with verapamil (4.66 v 4.10; P = .001). Baroreflex function was improved by both treatments; however, baroreflex sensitivity (BRS) was significantly higher with verapamil than with amlodipine (8.47 v 8.06 msec/mm Hg; P = .01). Plasma norepinephrine (NE) level was higher with amlodipine than with verapamil (1.59 v 1.32 nmol/L; P < .0001). Amlodipine induces a shift in sympathovagal balance, as measured by heart rate variability indices and plasma NE, toward sympathetic predominance compared with vagal predominance with verapamil. Short-term autonomic control of BP, as assessed by BRS, is more effectively improved by verapamil than by amlodipine. These contrasting effects on autonomic function suggest that the nondihydropyridine calcium antagonist verapamil may have additional beneficial effects beyond lowering BP compared with the dihydropyridine amlodipine.

Glucose disposal rates calculated from 60- to 90-minute isoglycemic hyperinsulinemic glucose clamp correlate with cardiovascular risk factors in borderline hypertensive young men.

The hyperinsulinemic glucose clamp is generally performed for at least 120 minutes, due to assumptions of steady-state. We were interested in relationships between glucose disposal rate (GDR) and cardiovascular risk factors, rather than a standard measure of insulin sensitivity per se. Therefore, we analyzed 120-minute clamps performed on borderline hypertensive, but otherwise healthy young men (n = 19). GDR was calculated at different time points and related to baseline cardiovascular risk factors and responses to a mental stress test (MST). The 60-, 90-, and 120-minute GDR correlated significantly with serum high-density lipoprotein (HDL) cholesterol (r=.59, r=.50, and r=.53, respectively), heart rate (HR) during MST (r = -.65, r = -.64, and r = -.58, respectively) and plasma epinephrine (Epi) (r = -.55, r= -.58, and r = -.56, respectively) and norepinephrine (NE) (r = -.52, r = -.49, and r = -.48, respectively) 1 minute after announcement of the MST (all P <.05). Although not statistically significant at all time points, similar relationships were observed between GDR and resting HR, systolic blood pressure (BP) at rest and during mental stress, body mass index (BMI), serum total cholesterol (Chol), serum triglycerides (TG), and blood hemoglobin (HgB), with remarkable consistency from about 40 to 50 minutes onwards. HDL cholesterol and Epi remained independent in stepwise multiple regression analyses with the 60-, 90-, and 120-minute GDR as dependent variables (all P <.05). We suggest that 60- to 90-minute glucose clamps may provide information about the relationship between insulin sensitivity and various cardiovascular risk factors in borderline hypertensive young caucasian men.

Awareness of high blood pressure influences on psychological and sympathetic responses.

The aim of the present study was to examine the effects of awareness of hypertension on psychological factors and whether there was an association between psychological and sympathetic responses. To avoid self-selection bias 32 19-yr old white men, all with mean blood pressure of 116 mm Hg were randomized into two groups. One group was informed that the blood pressure was elevated and asked to come to a second examination while the other was invited to take part in a coronary heart disease prevention program. A cold pressor test was undertaken and the subjects completed the Karolinska Scale of Personality (KSP). Assessed by the KSP, the informed group showed lower verbal aggression (p less than 0.01), irritability (p less than 0.05), monotony avoidance (p less than 0.05) and impulsiveness (p less than 0.05), higher detachment (p less than 0.05) but no significant differences in the other subscales like anxiety, psychasthenia or factors of hostility. Information significantly increased resting blood pressure and increments in heart rate and plasma adrenaline responses to cold pressor test. Thus, both psychological and sympathetic responses were influenced by awareness of high blood pressure. There were significant correlations between less assertive behaviour and increased plasma catecholamines.

Effects of anthocyanins on cardiovascular risk factors and inflammation in pre-hypertensive men: a double-blind randomized placebo-controlled crossover study.

High intake of fruits and vegetables is associated with reduced cardiovascular risk. A number of fruits and vegetables are rich in anthocyanins, which constitute a subgroup of the flavonoids. Anthocyanins have demonstrated anti-inflammatory and anti-oxidative properties, and anthocyanin-rich interventions have indicated beneficial effects on blood pressure and other cardiovascular risk factors. We assessed whether a purified anthocyanin supplement improves cardiovascular metabolic risk factors and markers of inflammation and oxidative stress in prehypertensive participants, and whether plasma polyphenols are increased 1-3 h following intake. In all, 31 men between 35-51 years with screening blood pressure >140/90 mm Hg without anti-hypertensive or lipid-lowering medication, were randomized in a double-blinded crossover study to placebo versus 640 mg anthocyanins daily. Treatment durations were 4 weeks with a 4-week washout. High-density lipoprotein (HDL)-cholesterol and blood glucose were significantly higher after anthocyanin versus placebo treatment (P=0.043 and P=0.024, respectively). No effects were observed on inflammation or oxidative stress in vivo, except for von Willebrand factor, which was higher in the anthocyanin period (P=0.007). Several plasma polyphenols increased significantly 1-3 h following anthocyanin intake. The present study strengthens the evidence that anthocyanins may increase HDL-cholesterol levels, and this is demonstrated for the first time in prehypertensive and non-dyslipidemic men. However, no other beneficial effects in the short term were found on pathophysiological markers of cardiovascular disease.

Effects of anthocyanins on blood pressure and stress reactivity: a double-blind randomized placebo-controlled crossover study.

High intakes of flavonoids are associated with reduced cardiovascular risk, and flavonoids such as cocoa and soy protein isolate have shown beneficial effects on blood pressure (BP). Anthocyanins constitute a flavonoid subgroup consumed in regular diets, but few studies have assessed the antihypertensive potential of anthocyanins. We aimed to assess whether high concentrations of relatively pure anthocyanins reduce BP and alter cardiovascular and catecholamine reactivity to stress. A total of 31 healthy men between 35-51 years of age with screening BP >140/90 mm Hg, not on antihypertensive or lipid-lowering medication, were randomised in a double-blind crossover study to placebo versus 320-mg anthoycanins twice daily. Treatment duration was 4 weeks, with a 4-week washout. Sitting and supine BP measurements, ambulatory BP recording and stress reactivity were assessed and analyzed by a paired sample t-test. In all, 27 patients completed all visits. Sitting systolic BP (primary endpoint) was 133 mm Hg after placebo versus 135 mm Hg after anthocyanin treatment (P=0.25). Anthocyanins did neither affect semiautomatic oscillometric BP measurements in the sitting or supine position nor 24-h ambulatory BP. No significant differences in stress reactivity were found across treatment periods. Overall, we conclude that high concentrations of these relatively pure anthocyanins do not reduce BP in healthy men with a high normal BP.

[Medical experiences from the Norwegian Nanga Parbat Expedition 1990]. / Medisinske erfaringer fra Den norske Nanga Parbat-ekspedisjonen 1990.

The author reports five cases of severe acute mountain sickness on a climbing expedition to Nanga Parbat (8,125 m) in Himalaya, Pakistan. One porter developed high altitude pulmonary edema, Grade IV, at an altitude of 4,200 m, and was successfully treated with oxygen, nifedipine and descent. One of the climbers developed a moderate pulmonary edema, and two moderate cerebral edema. All of these incidents occurred above 7,000 m, and responded to descent. A case of moderate high altitude sickness is also reported. Certain pathophysiological and symptomatic features of high altitude sickness are discussed.

Catecholamines, hypoxia and high altitude.

Hypoxia is a potent activator of the sympathetic nervous system by stimulating arterial chemoreceptors. However, out of 15 laboratory studies on the effects of acute and prolonged hypoxia on catecholamines, 14 failed to show any changes in plasma or urinary noradrenaline and only four studies showed significant increases in plasma or urinary adrenaline. By contrast, six out of eight studies on MSNA showed increased sympathetic nerve activity to the leg. An increased clearance of plasma catecholamines during hypoxia may be a possible explanation. Furthermore, many of the studies had limitations in a number of subjects and catecholamine assays used. Emotional aspects of the study protocols, which could contribute to the increase in adrenaline, was only assessed by sham runs in one chamber study. However, 13 out of 14 reviewed field studies on subjects staying for more than 1 week at high altitude, reported increased plasma or urinary excretion of noradrenaline which may be compatible with increased sympathetic activity. Adrenaline changed to a lesser degree. Out of seven studies on more short-term (4 h to 3 days) exposure to high altitude, only one demonstrated significantly increased plasma noradrenaline. In this study, however, several subjects had been exposed to high altitude less than 1 week before the experiment. In a new study on 12 climbers reported in this paper, a temporary reduction in plasma catecholamines was found 2 days after arrival at 4200 m. There was a steady increase towards normal levels after 1 week. Plasma vasopressin (AVP) increased suggesting a compensatory mechanism. Both plasma noradrenaline and adrenaline were positively correlated with oxygen saturation in these subjects. Thus, in previously unacclimatized subjects, short-term exposure to high altitude does not increase plasma catecholamines, rather plasma levels decreased. In addition to increased clearance, there is some evidence of reduced synthesis of catecholamines during short-term hypoxia. The oxygen sensitivity of tyrosine hydroxylase (TH) activity, may be one possible mechanism.