Borderline Hypertensive Group Research Articles

164 MAGNESIUM STATUS AND THERAPY IN BORDERLINE HYPERTENSION

Background, Design and Methods: The electrolyte magnesium plays an important role in the development of primary hypertension. Therefore we have measured plasma and intracdellular Mg++ levels in erythrocytes in 18 untreated borderline hypertensive patients and in 35 untreated normotensive healthy subjects as controls. Results: In patients intracellular Mg++ content was significantly lower (1.61+/−0.09 mmmol/l, mean +/− SD), than in controls (1.84+/−0.14 mmol, p < 0.05). After 12 − 15 weeks of an oral supplementation with 240 − 480 mg Mg++/day, the erythrocyte Mg++ content had increased significantly in the borderline hypertensive group (1.78+/−0.11 mmol/l) (p < 0.05). There was no significant difference between the normotensive and borderline hypertensive group in plasma Mg++ concentrations (0.87+/−0.13 versus 0.83+/−0.17 mmol/l). Systolic and diastolic blood pressure values of the borderline hypertensive group also normalized after oral Mg++ administration (before therapy: 147.6+/−8.5 / 87.2+/−4.4 mmHg, after therapy: 137.2+/−4.6 / 83.8+/−3.4 mmHg) (p < 0.05). After 18 − 21 weeks of magnesium-therapy in the hypertensives, blood pressure was 135.8+/−4.8 / 82.9+/−3.6 mmHg (p < 0.05) and plasma magnesium was 0.91+/−0.29 mmol/l. Conclusions: The clinical study presented here shows a positive effect of oral magnesium therapy in borderline hypertensives. This effect is time-dependent. Long-lasting magnesium therapy should be preferrend since the effects of magnesium supplementation in hypertension occur mainly after long-term treatment.

Prevalence and predictors of white-coat hypertension in a large database of ambulatory blood pressure monitoring

The objective of this study was to determine both the prevalence of white-coat effect and white-coat hypertension (WCH) and which selected clinical variables were predictors of WCH. A total of 2462 patients underwent ambulatory blood pressure monitoring either in borderline hypertension (group 1) or for assessment of antihypertensive treatment (group 2) or for hypotension (group 3). In the overall population 33.0% of patients showed WCH, 32.8% in group 1 and 37.0% in group 2. In multivariate analysis, sex and grade of hypertension were independent predictors of WCH in groups 1 and 2.

Increased left ventricular mass in children with autosomal dominant polycystic kidney disease and borderline hypertension

Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary condition that may be diagnosed in utero. Our goal was to evaluate symptoms of ADPKD in children, including left ventricular mass index (LVMI), renal volume, renal function and microalbuminuria in relation to systolic and diastolic blood pressure. Eighty-five children were stratified by blood pressure into three cohorts: hypertensive (95th percentile and over), borderline hypertensive (75-95th percentile) and normotensive (75th percentile and below). There were no differences in gender, age, height, renal function, or microalbuminuria between the groups. Both the hypertensive and borderline hypertensive children had a significantly higher LVMI than normotensive children, with no significant difference between hypertensive and borderline hypertensive groups. There was a significant correlation between renal volume and both systolic and diastolic blood pressures in all subjects. Renal volume in hypertensive children was significantly larger than in the borderline hypertensive group, with no significant difference between normotensive and borderline hypertensive groups. These findings show that an increase in LVMI may be detected earlier than an increase in renal volume in children with ADPKD and borderline hypertension, suggesting that close monitoring of cardiac status is indicated in these children.

Plasma asymmetric dimethylarginine and hyperemic myocardial blood flow in young subjects with borderline hypertension or familial hypercholesterolemia

ObjectivesThe goal of this study was to examine the relationship between plasma asymmetric dimethylarginine (ADMA) level and hyperemic myocardial blood flow (MBF) in subjects with borderline hypertension (BHT) and familial hypercholesterolemia (FH). BackgroundAsymmetric dimethylarginine is an endogenous competitive inhibitor of nitric oxide synthase that may modulate vascular function. MethodsWe measured plasma ADMA levels and myocardial flow in 77 young men (mean age 35 ± 5 years), including 47 healthy controls, 16 men with BHT, and 14 men with FH. Basal and dipyridamole-induced myocardial flow was measured using positron emission tomography. Plasma ADMA levels were measured using high-pressure liquid chromatography. ResultsAsymmetric dimethylarginine levels were significantly elevated in the BHT group compared with controls (0.59 ± 0.13 μmol/l vs. 0.43 ± 0.12 μmol/l, p < 0.001), and they had significantly lower dipyridamole flow (2.85 ± 1.20 ml/min/g vs. 3.69 ± 1.68 ml/min/g, p < 0.05). In a multivariate regression model adjusted for the study group, dipyridamole flow was inversely associated with ADMA (p < 0.05), age (p < 0.05), and apolipoprotein B concentration (p < 0.05). ConclusionsWe conclude that plasma ADMA concentration is related to dipyridamole-induced vasodilatory function in young men, independently of blood pressure elevation and hypercholesterolemia. Subjects with BHT have significantly increased plasma ADMA levels, which may partly explain the impaired hyperemic MBF in this condition.

Ambulatory blood pressure and Doppler echocardiographic indexes of borderline hypertensive men presenting an exaggerated blood pressure response during dynamic exercise

Borderline hypertension (BH) has been associated with an exaggerated blood pressure (BP) response during laboratory stressors. However, the incidence of target organ damage in this condition and its relation to BP hyperreactivity is an unsettled issue. Thus, we assessed the Doppler echocardiographic profile of a group of BH men (N = 36) according to office BP measurements with exaggerated BP in the cycloergometric test. A group of normotensive men (NT, N = 36) with a normal BP response during the cycloergometric test was used as control. To assess vascular function and reactivity, all subjects were submitted to the cold pressor test. Before Doppler echocardiography, the BP profile of all subjects was evaluated by 24-h ambulatory BP monitoring. All subjects from the NT group presented normal monitored levels of BP. In contrast, 19 subjects from the original BH group presented normal monitored BP levels and 17 presented elevated monitored BP levels. In the NT group all Doppler echocardiographic indexes were normal. All subjects from the original BH group presented normal left ventricular mass and geometrical pattern. However, in the subjects with elevated monitored BP levels, fractional shortening was greater, isovolumetric relaxation time longer, and early to late flow velocity ratio was reduced in relation to subjects from the original BH group with normal monitored BP levels (P<0.05). These subjects also presented an exaggerated BP response during the cold pressor test. These results support the notion of an integrated pattern of cardiac and vascular adaptation during the development of hypertension.

Prediction of blood pressure level and need for antihypertensive medication: 10 years of follow-up.

To evaluate the usefulness of blood pressure and its variability in the prediction of future blood pressure and need for antihypertensive medication. We used WHO criteria to classify, at baseline, 97 healthy untreated male volunteers as normotensive (n = 34), borderline hypertensive (n = 29) or mild hypertensive (n = 34), with casual measurements before intra-arterial 24 h ambulatory blood pressure monitoring. After 10 years of follow-up, 87 of the men (90%) were available and their blood pressure was recorded using casual measurements and non-invasive ambulatory 24 h monitoring. During the follow-up, the blood pressure classification deteriorated in 35 individuals (40%) and improved in six (7%) (McNemar test, P< 0.0001). In the borderline hypertensive group, 77% became hypertensive (P= 0.03). The 24 h mean systolic blood pressure was the best predictor of follow-up casual systolic (adj.R2 = 0.420) and 24 h systolic (adj.R2 = 0.540) blood pressure. The 24 h mean diastolic blood pressure was the best predictor of follow-up casual diastolic (adj.R2 = 0.301) and 24 h diastolic (adj.R2 = 0.292) blood pressure. The baseline casual systolic blood pressure also predicted the follow-up casual systolic blood pressure relatively well (adj.R2 = 0.356), but was clearly weaker for the follow-up 24 h systolic (adj.R2 = 0.275) blood pressure. The prediction of follow-up casual diastolic (adj.R2 = 0.259) and follow-up 24 h diastolic (adj.R2 = 0.214) blood pressure by baseline casual blood pressure was even weaker. The means and variabilities of the 24 h, daytime, and night-time blood pressures were the best predictors of the need for antihypertensive medication (Cox-Snell R2 = 0.399). The characteristics of the individual did not significantly predict future blood pressure and the need for antihypertensive medication. The 24 h mean blood pressure was an excellent predictor of the future blood pressure and the need for antihypertensive medication. Prediction of antihypertensive medication was further improved by also using blood pressure variability. Systolic blood pressure was more predictable than diastolic blood pressure.

The Effect of Resistance Exercise on Recovery Blood Pressure in Normotensive and Borderline Hypertensive Women

Nine normotensive and 7 borderline hypertensive women were studied to investigate the effects of an acute bout of resistance exercise on recovery blood pressure. The investigation was conducted over 3 sessions. During the first session, subjects were assessed for muscular strength while performing the following exercises: chest press, seated leg press, biceps brachii curl, knee extension, and triceps brachii extension. In a subsequent session, subjects completed 3 circuits of the aforementioned exercises at 50% (15 repetitions) of the estimated 1 repetition maximum (1RM), followed by a 60-minute recovery period. Systolic (SBP) and diastolic (DBP) pressures were assessed via auscultation at 10-minute intervals throughout the recovery period. Subjects were also monitored in a similar manner on a control day in which exercise was excluded. The data were analyzed using a 3-way analysis of variance (ANOVA) with a predetermined alpha level of p < or = 0.05. Women in the borderline hypertensive group exhibited higher SBP (126.5 +/- 3.1 mm Hg) and higher DBP (85.4 +/- 1.8 mm Hg) than their normotensive counterparts (103.5 +/- 2.7 mm Hg; 69.3 +/- 1.6 mm Hg) throughout the study. SBP was significantly lower during recovery from the exercise session (113.8 +/- 2.1 mm Hg) compared with the control session (116.1 +/- 2.1 mm Hg). DBP did not vary between sessions. Although blood pressure was higher in borderline hypertensive subjects, the response of both groups during seated recovery was the same. In conclusion, a single bout of resistance exercise appears to invoke a slight systolic hypotensive response during recovery in normotensive and borderline hypertensive women.

Circadian systemic haemodynamics in borderline and mild hypertension.

Circadian variations in blood pressure (BP), stroke volume (SV), heart rate (HR), cardiac output (CO) and total peripheral resistance (TPR) were determined by a pulse contour method from the intra-arterial pulse wave in 32 normotensive (NT), 32 borderline hypertensive (BHT) and 31 hypertensive (HT) middle-aged men. Daytime averages were used as the reference levels. The nocturnal decrease in BP and HR were similar in the three groups. In the night, SV did not change in the NT group, but was increased in the BHT and HT groups. The nocturnal increase in SV may reflect reduced venous capacity causing increased cardiac filling. As a consequence of the difference in SV, the nocturnal CO fall was diminished in the HT group as compared with the NT group. Moreover, TPR had a tendency to decrease in the HT group, which may be considered as a baroreflex response to buffer the expected rise in BP. Five years later, 25 NT, 24 BHT and 19 HT subjects were reassessed using casual BP measurements. In the NT and BHT groups, six and 17 subjects, respectively, had progressed to hypertension. In a logistic regression model for those who became HT, the nocturnal increase in SV was a significant predictor for future hypertension. In conclusion, the results suggest that circadian systemic haemodynamics may be altered before BP is markedly elevated, and that haemodynamic studies might be useful in predicting the development of sustained hypertension.

Antibodies to platelet-activating factor are associated with borderline hypertension, early atherosclerosis and the metabolic syndrome.

Platelet-activating factor (PAF) is a phospholipid inflammatory mediator which is synthesized by a variety of cells, including monocytes and endothelial cells, and PAF can be retained in activated endothelial cell membranes. Furthermore, PAF-like lipids are produced in other phospholipid membranes as in oxidized LDL. Atherosclerosis is a chronic inflammation in the artery wall, but little is known about the role of immune reactions in the early stages of development of cardiovascular disease. In the present study we investigated if there are antibodies to PAF (aPAF) that may play a role in borderline hypertension and early atherosclerosis. Seventy-three men with borderline hypertension (BHT) and 73 age-matched normotensive (NT) men (diastolic blood pressure 85-94 and <80 mmHg, respectively) were recruited from a population screening programme. Antibody levels were determined by use of ELISA. Carotid intima-media (IM)-thickness and atherosclerosis was determined by B-mode ultrasonography. BHT men had 49.3% higher aPAF levels of IgG class than NT controls (P = 0.0007). Antibodies to the biologically inactive lysoPAF did not differ between BHT and NT group. aPAF levels were associated with IM-thickness in the left (P = 0.02) and right (P = 0.009) carotid artery. Furthermore, aPAF levels were enhanced in individuals with the metabolic syndrome (n = 44) as compared to those without (n = 102; P = 0.009), and also significantly associated with insulin levels (P = 0.02) and insulin resistance (P = 0.02). aPAF antibodies may reflect early vascular changes and thus serve as novel markers for disease, and they may also be pathogenic, by eliciting an inflammatory reaction in the vascular wall.

Effects of naloxone on hemodynamic and sympathetic nerve responses to pain in normotensive vs. borderline hypertensive men

Pain sensitivity decreases with increasing resting blood pressure. This blood pressure–pain interaction may be mediated by endogenous opioids which have been shown to affect both blood pressure and nociception. To test this hypothesis, we measured mean arterial blood pressure (MAP), central venous pressure (CVP), heart rate (HR), muscle sympathetic nerve activity (MSNA), serum catecholamines, and individual pain rating scales during 2 min periods of noxious mechanostimulation (skin fold pinching) in nine young (26±2 year), male normotensive (NT) subjects and in 12 age and weight matched males with borderline hypertension (BHT). Measurements were performed before and after the i.v. administration of naloxone (0.15 mg/kg) and placebo in a randomized double-blind cross-over trial. In the pre-naloxone trials, pain led to similar changes in MAP, CVP, MSNA and plasma catecholamines in the two groups except for a higher increase in HR in the BHT group as compared to the NT group (3±1 vs. 1±1 bpm; P<0.005). Opioid blockade with naloxone increased MSNA responses to pain in the NT group (from 5±1 to 9±1 bursts/min, and, from 100±23 to 204±36 units/min, respectively; P<0.05) but did not significantly affect the MSNA response to pain in the BHT group. Pain induced responses of MAP, CVP, and catecholamines were not altered by naloxone in either group. Overall, there was a highly significant inverse correlation between pain perception and resting blood pressure which was not significantly affected by naloxone. The BHT subjects exhibited a lower pain perception compared to the NT subjects ( P<0.005). Naloxone increased pain rating in the NT group (from 194±9 to 218±13; P<0.005) but not in the borderline hypertensive group (160±8 vs. 168±10; P=0.36). Except for a decreased HR response in the BHT group, placebo had no effect on the responses to pain. Our data do not indicate a major role of the endogenous opioid system for the blood pressure–pain interaction in man. Endogenous opioids affect pain perception and sympathetic nerve activity responses to pain in normotensive men but their activity seems to be attenuated in borderline hypertensive subjects. Therefore, the lower pain sensitivity in human essential hypertension is probably mediated by non-opioid mechanisms.

Psychophysiologic sensitization to headlight glare among professional drivers with and without cardiovascular disease.

Previous studies have shown that young, healthy professional drivers show heightened central nervous system arousal and cardiovascular hyperreactivity to simulated headlight glare. Electroencephalographic and cardiovascular response and recovery to simulated headlight glare (the glare pressor test) were examined in 4 groups of male professional drivers (age 25-52 years)--12 with ischemic heart disease (IHD), 12 with hypertension (HTN), 10 with borderline hypertension (BHTN), and 34 who were healthy--and in 23 non-professional driver controls--with the aim of assessing sensitization to this night driving stressor in relation to degree of cardiovascular disease severity. After glare exposure the IHD drivers showed the most pronounced alpha blockade, a rise in diastolic blood pressure (DBP; p < .05), and, unlike the other groups, a persistent fall in finger pulse volume (p < .02). The BHTN group reacted initially with DBP rise and finger pulse drop (ps < .05 and .02, respectively), mainly without central nervous system arousal. The DBP remained constant in normotensive professional drivers older than 40. The drivers' cardiovascular responses to glare were inversely related to reported stressors and subjective experience. Anxiety trait and long work hours were associated with heightened central arousal to glare in professional drivers. The results suggest that there may be progressive degrees of sensitization to glare exposure in these samples, with the least among normotensive professional drivers older than 40, moderate levels in borderline hypertensives, and the most severe in drivers with IHD.

SYMPATHETIC OVERACTIVITY AND CORONARY RISK IN HYPERTENSION

Tecumseh, Michigan. Nearly one thousand subjects were enrolled into the study and anthropometric, hemodynamic and metabolic data were collected at several time points. When first examined as children those subjects who were ultimately to develop borderline hypertension had significantly faster heart rates than their future normotensive counterparts despite having comparable blood pressures as children.( 1) As they aged the difference between the pulse rate was maintained and the blood pressure in the borderline hypertensive group had become elevated. When examined as adults (1 8-42 years) the differences in pulse rate and blood pressure persisted between the groups and elevated plasma noradrenaline was demonstrated in the hyperkinetic (high cardiac output, increased heart rate) hypertensive subjects. An significant increase in cardiac risk factors was found in the hypertensive group as a whole and also in the subpopulation of pure hyperkinetic hypertensive subjects (2) and a strong correlation between diastolic blood pressure and these risk factors was also found (3). This data suggests that there was a relative overactivity of the sympathetic nervous system present from an early age in the subjects who were to develop borderline hypertension and that this persisted into at least early adulthood. It also raises the intriguing possibility that sympathetic excess could not only be responsible for the blood pressure elevation in these subjects but also independently result in the increase in coronary risk factors. A hypothetical schema for just such an association will be described where excess sympathetic tone is the underlying pathophysiological state that leads to an increased tendency to atherosclerosis and insulin resistance as well as a propensity to coronary thrombosis, coronary spasm and arrhythmia's. Insulin resistance has been shown to be associated with hypertension (4) and is accompanied by an increased coronary morbidity (5). Excess sympathetic tone may produce insulin resistance by promoting a-adrenergic vasoconstriction and reducing the delivery of insulin and glucose to skeletal muscle, which is thought to be the site of insulin resistance in hypertension. Jamerson 's work (6) lends support to this concept when it was demonstrated that decreased blood flow in the human forearm produced by reflex activation of the sympathetic nervous system results in decreased glucose utilization, a condition analogous to insulin resistance. This type of sympathetically mediated insulin resistance may be compounded by the trophic effects of elevated insulin on the vascular wall (7) and by vascular rarefaction which has been documented to occur in hypertension (8). Further evidence for a role of the sympathetic nervous system in altered insulin sensitivity in

Stress-induced blood pressure measurements predict left ventricular mass over three years among borderline hypertensive men.

Exaggerated cardiovascular reactivity has been implicated in the development of left ventricular hypertrophy. The aim of the present study was to investigate the predictive value of casual clinic, 24‐h ambulatory blood pressure and stress‐induced blood pressure measurements in the laboratory for left ventricular structures over a 3‐year period in a group of middle‐aged borderline hypertensive men. The stress test included a pretask resting period and two tasks, mental arithmetic and isometric muscle contraction. Left ventricular wall thickness was assessed by M‐mode echocardiography. All stress‐induced blood pressure levels and reactivity measures as well as ambulatory systolic blood pressure and mean arterial pressure levels were significantly correlated with left ventricular mass index (LVMI) 3 years later (r = 0.31–0.50), whereas there were no significant correlations between casual clinic or resting BP measurement and LVMI. A stepwise multiple regression analysis with LVMI at the 3‐year follow‐up as the dependent variable was applied. Baseline LVMI was entered as a forced variable and explained 24% of the variance in LVMI. Mean arterial blood pressure reactivity in the laboratory was the strongest additional independent variable, and added 15% to the prediction of LVMI 3 years later. Using a median split approach, the borderline hypertensive group was divided into high and low BP reactors. High and low BP reactors did not differ at initial baseline, but at the 3‐year follow‐up the high reactive group had significantly larger LVMI than the low reactive group. Results from the present study suggest that stress‐induced BP reactivity measurements predict the development of LVMI better than casual or resting BP measurements. Thus, measuring BP during standardized stress tests could be a method used to identify borderline hypertensive individuals at increased risk of developing left ventricular hypertrophy.

Stress-Induced Laboratory Blood Pressure in Relation to Ambulatory Blood Pressure and Left Ventricular Mass Among Borderline Hypertensive and Normotensive Individuals

Our primary aim in the present study was to investigate the association between blood pressure measured in the laboratory and in the ambulatory state in a group of middle-aged borderline hypertensive men and age-matched normotensive control subjects. In addition, we examined the relation between stress-induced blood pressure measurements and left ventricular mass. Blood pressure and heart rate were measured noninvasively during a standardized laboratory stress protocol and four times per hour throughout 24 hours. Borderline hypertensive subjects had significantly higher systolic and diastolic pressures than normotensive subjects during both the daytime (systolic pressure, 141.1 +/- 9.7 versus 130.9 +/- 8.6 mm Hg; diastolic pressure, 88.8 +/- 7.0 versus 79.4 +/- 6.2 mm Hg, P < .001) and nighttime (systolic pressure, 114.0 +/- 9.9 versus 107.1 +/- 8.3 mm Hg; diastolic pressure, 71.5 +/- 7.5 versus 64.6 +/- 7.2 mm Hg, P < .001). The borderline hypertensive group also displayed increased systolic pressure reactivity in the laboratory compared with the normotensive group. The groups did not differ significantly in left ventricular mass (index). In both borderline hypertensive and normotensive individuals, blood pressure levels during stress testing were closely related to ambulatory blood pressure levels (r = .51 to .82). Furthermore, stress-induced blood pressure levels were significantly correlated to left ventricular mass in borderline hypertensive (r = .33 to .40) but not normotensive subjects. Since stress-induced blood pressure levels were significantly associated with both ambulatory blood pressure levels and left ventricular mass in borderline hypertensive subjects, the addition of standardized stress testing to casual blood pressure measurements may improve risk estimation.

Elevation of plasminogen activator inhibitor 1 in borderline hypertension is linked to concomitant metabolic disturbances.

In the present study we investigated plasma levels of plasminogen activator inhibitor 1 (PAI-1), fibrinogen and von Willebrand factor (vWF) in borderline hypertensive (BHT) men [diastolic blood pressure (DBP) 85-94 mmHg, n = 75] and age-matched normotensive (NT) control subjects (DBP < or = 80 mmHg, n = 75), in relation to smoking, body mass index (BMI) and fasting lipoprotein and insulin levels. PAI-1 levels were elevated in the BHT group [16.3 vs. 13.7 arbitrary units (AU), P = 0.032], whereas levels of fibrinogen and vWF were similar in the two groups. The PAI-1 elevation was even more pronounced in dyslipidaemic BHT subjects than in normolipidaemic NT subjects (20.0 vs. 10.3 arbitrary units (AU), P = 0.001). PAI-1 levels showed strong correlations with insulin, lipoproteins and BMI (P < 0.01-0.001), but not with DBP. The results show that disturbances in the fibrinolytic system appear even in borderline hypertension. The elevation of PAI-1 levels seems to be more strongly linked to concomitant metabolic disturbances than to blood pressure levels.

Hemodynamic and sympathetic nerve responses to painful stimuli in normotensive and borderline hypertensive subjects

Observations in animals and humans show that pain sensitivity might be lower (and pain tolerance higher) in hypertensive as compared to normotensive subjects. One hypothesis, derived from experimental studies, assumes that enhanced activation of baroreceptors leads to an enhanced central inhibition. A central hypothesis assumes changes in the central (endogenous) control of the nociceptive system. To investigate these two hypotheses we quantitatively assessed the minute-by-minute changes in mean arterial pressure (MAP), central venous pressure (CVP) heart rate (HR), muscle sympathetic nerve activity (MSNA), and individual pain ratings during noxious mechanostimulation in 10 normotensive (NT) and 13 borderline hypertensive (BH) subjects. Linear regression analysis indicated a close negative correlation for the overall data between resting levels of MAP and pain ratings (r = −0.57, P < 0.0001). The BH group exhibited a lower pain sensitivity compared to the NT group (P < 0.001). The extent of baroreceptor activation during the application of pain was not different between the two groups (P = NS) as assessed by almost identical increases in MAP (+8 ± 1 vs. +9 ± 1 mmHg NT vs. BH group), CVP (+0.7 ± 0.1 vs. +0.5 ± 0.1 mmHg), HR (+2 ± 1 vs. +2 ± 1 beats/min), and MSNA (+5 ± 1 vs. +4 ± 1 bursts/min). The NT subjects exhibited significant correlations between the pain ratings and the increases in MAP (r = +0.52; P < 0.05) and MSNA (r = +0.49; P < 0.05) whereas the BH subjects did not show such a relationship. Thus, the increased pain tolerance in human hypertension cannot be explained by hemodynamically mediated differences in the activation of baroreceptors or by an altered baroreflex sensitivity during the application of pain. We conclude, that the reduced pain sensitivity in hypertensive humans is more likely related to central changes.

Forearm beta adrenergic receptor-mediated vasodilation is impaired, without alteration of forearm norepinephrine spillover, in borderline hypertension.

Impaired beta adrenoceptor-mediated vasodilation associated with enhanced sympathetic activity has been reported in established hypertension. We examined whether altered beta adrenoceptor-mediated vasodilation occurs early in the disease process, when structural vascular changes are likely to be less marked, by measurement of forearm blood flow by strain gauge plethysmography after the intraarterial administration of increasing doses of a beta receptor agonist, isoproterenol, in eight subjects with borderline hypertension (BHT) and 13 normotensive (NT) controls. To determine the role of sympathetic activation in the regulation of responsiveness, we measured local sympathetic activity in the forearm by a radioisotope dilution technique. Vasodilation in response to isoproterenol, measured either as changes in forearm blood flow or forearm vascular resistance, was impaired in the BHT group so that flow at the highest dose of isoproterenol (400 ng/min) increased less (15.2 +/- 1.5 ml/100 ml per min) than in the NT group (24.4 +/- 2.4 ml/100 ml per minute) (P < 0.001). Although, systemic norepinephrine spillover was significantly greater in BHT, the difference in blood flow response to isoproterenol was not accounted for by increased local sympathetic activity since forearm norepinephrine spillover at baseline (BHT 1.0 +/- 0.4 ng/min vs. NT 0.64 +/- 0.13 ng/min) and after the administration of isoproterenol 60 ng/min (BHT 5.2 +/- 1.4 ng/min vs. NT 6.0 +/- 1.5 ng/min) and 400 ng/min (BHT 13.5 +/- 2.9 ng/min vs. NT 16.5 +/- 2.7 ng/min) did not differ between the two groups. We therefore conclude that vasodilation in response to isoproterenol is impaired in subjects with BHT and that this impairment is not explained by locally increased basal, or stimulated, sympathetic activity.

Vascular compliance in sodium-sensitive and sodium-resistant borderline hypertensive patients

Recently, we demonstrated a reduction in the compliance of the carotid, femoral and brachial arteries in sodium-sensitive subjects who had consumed a regular sodium intake of approximately 120 mmol per day, as compared to both sodium-resistant borderline hypertensive subjects and normotensive controls. Venous compliance was not different between the two borderline hypertensive groups and was only slightly lesser than in controls. Large artery compliance was studied using a non-invasive ultrasound vessel wall movement detector system, while venous compliance was determined by means of strain gauge plethysmography. The borderline hypertensive subjects were subsequently treated with enalapril 10 mg/day, felodipine 5 mg/day or placebo during six months. Despite similar reductions in blood pressure, enalapril induced a significant increase of the muscular femoral and brachial artery compliance, but not of the elastic carotid artery, while felodipine did not influence large artery compliance at all in the sodium-sensitive group. The effect of enalapril on muscular artery compliance was established through a dose-dependent increase in distension and not through a change in arterial diameter. Arterial compliance was not influenced by either of the drugs in the resistant group. Venous compliance was also not altered by the medication. In conclusion, femoral and brachial artery compliance in sodium-sensitive borderline hypertensive subjects, which was found to be lower than that of sodium-resistant subjects, improved with antihypertensive treatment with enalapril but not with felodipine, despite the similar reductions in blood pressure induced by both drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid intima-media thickness and plaque in borderline hypertension.

In this study, we investigated intima-media thickness and plaque occurrence in the carotid arteries of men with borderline hypertension compared with that in normotensive control subjects and investigated the relations of these variables to atherosclerotic risk factors. Using B-mode ultrasonography, we compared carotid artery intima-media thickness and plaque occurrence in men with borderline hypertension (diastolic blood pressure of 85 to 94 mm Hg, n = 73) with that in age-matched normotensive control subjects (diastolic blood pressure of 80 mm Hg, n = 72). We evaluated the relationships of intima-media thickness and plaque occurrence to atherosclerotic risk factors such as age, smoking, lipoprotein levels, and fasting insulin levels. The borderline hypertensive group exhibited a slight increase in overall intima-media thickness (0.73 versus 0.69 mm, P = .07), which was most evident in the right carotid artery (0.72 versus 0.67 mm, P < .05). There were more borderline hypertensive subjects with plaque (26% versus 16%, NS), again more evident on the right side (18% versus 6%, P < .05). Age and high-density lipoprotein cholesterol were consistently related to intima-media thickness (t = 1.94 to 3.24 and t = -2.25 to -2.69, respectively, P < .05), whereas age was the only significant determinant for plaque/nonplaque (F = 6.4, P < .05). In addition, there was a significant difference in intima-media thickness between the right and left carotids, irrespective of group (F = 4.43, P < .05). Our results indicate that vascular structural changes occur even in borderline hypertension, although this seems more related to general atherosclerotic risk factors than to blood pressure alone. Additionally, a possible difference in the development of atherosclerotic lesions of the left and right carotid arteries is suggested, emphasizing the importance of measuring and reporting values from both sides when studying carotid intima-media thickness and plaque occurrence.

Increased basal concentrations of plasma endothelin in borderline hypertension

There is evidence for an altered endothelial function in established hypertension but little is known about endothelial function in borderline hypertension. It has also been suggested that the early stages of hypertension are characterized by an increased sympathetic drive. To investigate whether alterations in endothelin, neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) are already present in the borderline hypertensive stage. A case-control study of age-matched men recruited from a population screening programme. Seventy-five men with stable borderline hypertension [diastolic blood pressure (DBP), 85-94 mmHg] and 75 age- and sex-matched normotensive controls (DBP < or = 80 mmHg) were investigated. Plasma samples were drawn in a standardized fashion, and extracted and analysed using competitive radio immunoassays. Basal concentrations of NPY and CGRP were similar in the two groups (28.4 versus 26.7 pmol/l and 24.2 versus 21.7 pmol/l, respectively). Basal concentrations of endothelin were significantly higher in the borderline hypertensive group (2.0 versus 1.5 pmol/l, P < 0.0001). These results suggest that a disturbed endothelial function, represented by endothelin, could be involved in the early hypertensive processes. They also suggest that these changes could be present before the basal sympathetic/parasympathetic drive alters, warranting further research into this area.