Evidence for altered vascular reactivity in sodium-sensitive young subjects with borderline hypertension

To assess mechanisms associated with the pressor effects of a high sodium diet in susceptible individuals, the hemodynamic and hormonal effects of sodium depletion and repletion were studied in 33 normal subjects and 30 subjects with borderline hypertension. The hypertensive group had significantly higher mean arterial pressure, weight, hematocrit, and upright plasma renin activity. Forearm hemodynamics were measured during periods of ad lib diet, 10 mEq, and 200 mEq sodium diet. The fall in forearm resistance during reactive hyperemia was inversely related to mean arterial pressure at rest (R = .400, p less than .005) and rose significantly in hypertensive subjects during salt depletion, 39 +/- 3.6 to 61 +/- 6.1 mmHg/ml/min/100 g (p less than .05). Sodium sensitivity in either normotensive or borderline hypertensive subjects was defined as an increase in mean blood pressure of more than 5% when sodium repleted. The individuals who were sodium sensitive had a higher forearm vascular resistance during sodium depletion than those who were sodium resistant, 67 +/- 10.5 versus 45 +/- 4.1 mm/ml/min/100 g (p less than .03). We conclude that young individuals with borderline hypertension already have alterations in vascular reactivity. This trait is shared by normotensive individuals whose blood pressure rises in response to sodium.     

Increased sympatho-adrenomedullary activity in young patients with borderline hypertension: hyperresponses to isometric stress and glucagon injection

The purpose of this study was to estimate the sympatho-adrenomedullary activity in young patients with borderline hypertension (BHT, n=23), compared with age-matched normotensive subjects (NT, n=9), so that two studies were performed as follows: they were subjected to isometric stress, by maintaining handgrip at the 30% level of maximal voluntary contraction for three minutes. With the exercise blood pressure and pulse rate increased to the same degree in BHT as in NT. In contrast, the response of plasma total catecholamine (plasma epinephrine plus norepinephrine) at the end of this isometric exercise was greater in BHT than in NT (93.0 +/- 12.6 in BHT vs. 47.1 +/- 15.4pg/ml in NT). Moreover, the effects of intravenous glucagon injection (1 USP unit) were studied in twelve subjects of BHT (n = 12) and all of NT (n = 9). The injection of glucagon induced a transient increase in pulse rate, but there was no significant difference in the elevation of pulse rate with glucagon between BHT and NT. Plasma epinephrine also increased temporarily, and returned to the baseline within ten minutes after injection. The increments of plasma epinephrine at two and three minutes after injection were significantly greater in BHT than those in NT: 44.1 +/- 12.3 vs. 5.1 +/- 4.4pg/ml, and 68.9 +/- 13.2 vs. 32.1 +/- 8.9 pg/ml, respectively. Thus, patients with borderline hypertension had the augmented response of plasma catecholamine to both isometric exercise and glucagon stimulation. Evidence presented suggests that the responses of sympathetic nervous system and adrenal medulla to stress are increased in young patients with borderline hypertension. Moreover, the augmented response of sympatho-adrenomedullary system to stress may be involved in the development of essential hypertension.     

Effects of increased adrenomedullary activity and taurine in young patients with borderline hypertension

Recent studies showed that taurine, a sulphonic amino acid, could decrease blood pressure and increase sympathoadrenal tone in DoCA-salt-treated hypertensive rats. To determine whether taurine exerts its antihypertensive action in man in a similar fashion, we studied the effect of oral administration of taurine (6 g for 7 days) on blood pressure and plasma catecholamines in 19 young patients with borderline hypertension in a double-blind, placebo-controlled fashion. Systolic blood pressure in the 10 patients who were treated with taurine decreased by 9.0 +/- 2.9 mm Hg (mean +/- SE; p less than .05 by paired t test), compared with a 2.7 +/- 2.3 mm Hg decrease (NS) in the nine patients treated with placebo and diastolic blood pressure in the taurine-treated patients decreased by 4.1 +/- 1.7 mm Hg (p less than .05) compared with 1.2 +/- 3.0 mm Hg (NS) in the placebo-treated subjects. In the patients receiving taurine plasma epinephrine (E) decreased significantly, with a negligible decrease in plasma norepinephrine (NE). The effect of taurine on plasma catecholamines and the response of plasma E after the stimulation with glucagon was also studied in 12 borderline hypertensive and nine age-matched normotensive subjects. Basal plasma E was significantly higher in borderline hypertensive than in normal subjects, but basal plasma NE did not differ in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endothelium-dependent vasodilation in normotensive subjects with a familial history of essential hypertension and in young subjects with borderline hypertension

OBJECTIVE: To investigate if young normotensive subjects with a familial history of essential hypertension (FHH) or young borderline-hypertensive (BHT) subjects have a defect endothelial function. METHODS: Fifteen young (26 +/- 4 years) healthy normotensive (115 +/- 8/71 +/- 6 mmHg) subjects with a FHH, 31 matched healthy normotensive subjects without FHH and seven BHT (143 +/- 12/92 +/- 2 mmHg), otherwise healthy, young males underwent evaluation of endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIDV), by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium nitroprusside (SNP, evaluating EIDV) in the forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. RESULTS: Although there was no significant difference between normotensive subjects with and without a FHH regarding FBF during vasodilation induced by MCh or SNP, the subjects with a FHH presented a significantly suppressed endothelial function index, calculated as the ratio between EDV and EIDV, when compared to subjects without FHH (1.04 +/- 0.15 vs. 1.24 +/- 0.23, p < 0.01). Also in the group of BHT subjects, the endothelial function index was suppressed (1.01 +/- 0.18, p < 0.01), in this case due to a significantly attenuated EDV (p < 0.05), when compared to male subjects without a FHH. CONCLUSION: The present findings suggest an early occurrence of endothelial dysfunction in the development of essential hypertension.     

The hemodynamics in young patients with borderline hypertension

Hemodynamics in supine position were studied echocardiographically in 56 young patients with borderline hypertension and 56 age-matched normotensive subjects. In hypertensive patients, the cardiac index (CI) did not increase, but the total peripheral resistance (TPR) increased significantly (p less than 0.005). The hypertensive patients were classified into 2 groups, according to the level of the CI. In patients in group A ("normal" CI), the CI, heart rate and the mean circumferential fiber shortening velocity (mVCF) were normal, but the TPR was increased significantly. In patients in group B ("high" CI), the CI, heart rate and the mVCF increased significantly (hyperkinetic state), but the TPR was normal. Plasma renin activity (PRA) was significantly higher in patients in group B than the normal subjects, but the level of PRA in patients in group A was normal. These findings support the hypothesis that sympathetic nervous activity increases in patients in group B, but not in those in group A. Therefore, this study provides evidence that the TPR is abnormal in patients with borderline hypertension, and an impaired neurogenic activity seems to be important in the early stage of hypertension, as in borderline hypertension associated with a hyperkinetic circulatory state (group B).     

Exercise response in young women with borderline hypertension

We compared the response to dynamic exercise in 157 females (mean age 19 +/- 3 years) with borderline hypertension (BH) to findings in 105 normotensive controls. Near-maximal physical working capacity was 90 +/- 17 W in females with BH and 71 +/- 23 W for the controls (p less than 0.001). Mean heart rate, systolic and diastolic blood pressure, and pulse pressure levels both at rest and at exercise were significantly higher in BH patients (p less than 0.001 for all). Mean change between rest and exercise for all the above parameters was not significantly different among BH patients compared with controls. Nonspecific ST-T changes at rest (p less than 0.001) and exercise (p less than 0.005) were more common and mean corrected QT interval was significantly longer (p less than 0.001) in BH patients. The parallel exercise response that we found in BH and normotensives would not appear to substantiate the view that ergometry is particularly useful as a modality for diagnosing hypertension in young females.     

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

OBJECTIVE: The 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). METHODS: Asymmetric dimethylarginine is an endogenous competitive inhibitor of nitric oxide synthase that may modulate vascular function.We 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. RESULTS: Asymmetric dimethylarginine levels were significantly elevated in the BHT group compared with controls (0.59 +/- 0.13 micromol/l vs. 0.43 +/- 0.12 micromol/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). CONCLUSIONS: We 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.     

Pathogenesis of borderline arterial hypertension in young persons

A total of 1000 students were screened, and borderline arterial, hypertension (BAH) was found in 152 of those. The investigation of microcirculation (by conjunctive biomicroscopy), central hemodynamics and physical stress tolerance showed increased minute blood volume in the absence of adequate arteriole dilatation to be the primary factor in BAH pathogenesis. Physical stress tolerance was similar in BAH and normotensive subjects. BAH subjects showed a specific pattern of cardiovascular response to muscular work.     

Attenuation of the microcirculation in young patients with high-output borderline hypertension

Previous studies have shown abnormalities of the microvasculature in the spontaneously hypertensive rat and human subjects with established hypertension. We have studied the conjunctival microvasculature in relation to systemic and forearm hemodynamics in 24 normal subjects (NL) and 10 subjects with intermittent elevation of blood pressure (BHT). Macrophotographs of the conjunctival circulation were measured for arteriolar diameter and density of arterioles, capillaries, and venules. Blood pressure was measured by Arteriosonde, cardiac index by echocardiography, and forearm hemodynamics by mercury-filled strain-gauge venous occlusion plethysmography. Average diastolic blood pressure in the NL group was 74 +/- 1.7 mm Hg, while that of the BHT subjects was 89 +/- 3.1 mm Hg (p less than 0.005). Capillary density, venous density, and total vascular density were significantly lower in the BHT than NL group, while arteriolar density did not differ significantly. Cardiac index was significantly higher, and peripheral vascular resistance significantly lower, in the BHT as compared to the NL subjects. Forearm blood flow was higher in the NL subjects. The diameter of the preterminal arterioles of the BHT subjects was 27% greater than NL (p less than 0.02). The capillary density was inversely related to the cardiac index (r = -0.482, p less than 0.01), but was not related to blood pressure (r = -0.207). We conclude that the high cardiac output phase of early essential hypertension in humans is accompanied by a reduction in the number of filtering capillaries, and that the rarefaction of capillaries is more closely related to the elevation of cardiac output than to raised blood pressure.     

临界性高血压患者冠状动脉血流储备功能的研究

目的 :了解无症状临界性高血压患者是否有冠状动脉功能异常。方法 :经食管超声心动描记术研究 2 0例正常人 (正常对照组 )及 17例无症状临界性高血压患者 (临界性高血压组 )的冠状动脉血流储备 (CFR)。以潘生丁静脉注射后和静息时舒张期的最大血流速度比率 (D/R PDV)和收缩期最大血流速度比率 (D/R PSV )作为CFR指标。结果 :1两组受检者静息时的 PDV无显著性差异〔(43± 10 ) m m/s∶ (46± 8) mm /s,P >0 .0 5〕;2静脉注射潘生丁后临界性高血压组的 D/R PDV、D/R PSV较正常对照组明显减少 ,两组之间有显著性差异 (D/RPDV:2 .2 5± 0 .36∶ 2 .86± 0 .42 ,D/R PSV:2 .0 0± 0 .2 6∶ 2 .5 6± 0 .41,P<0 .0 5 )。结论 :无症状临界性高血压患者 CFR能力降低。     

Absence of post exercise hypotension and sympathoinhibition in normal subjects: additional evidence for increased sympathetic outflow in borderline hypertension

OBJECTIVE: In young men (mean age 25 years) with borderline hypertension the authors have documented a reduction in systolic blood pressure and muscle sympathetic nerve activity 60 mins after 45 mins of submaximal treadmill exercise. The aim of this study was to determine if post exercise hypotension occurs in normotensive young men, and if so, if it is accompanied by a decrease in sympathetic nerve activity. DESIGN: Replicating a previous protocol, the authors recorded blood pressure, heart rate, plasma noradrenaline and muscle sympathetic nerve activity (microneurography; peroneal nerve) before and 60 mins after submaximal treadmill exercise. SUBJECTS: Ten healthy male volunteers (mean age 28 +/- 5 years). INTERVENTION: Forty-five minutes of treadmill exercise at 70% of resting heart rate reserve. MAIN RESULTS: In contrast to borderline hypertensive subjects, prior exercise had no effect on either systolic or diastolic blood pressure or muscle sympathetic nerve activity in healthy volunteers. Plasma noradrenaline concentrations were similar before and after exercise. Resting heart rate (56 +/- 3 versus 70 +/- 3 beats/min; P less than 0.002), and sympathetic burst frequency (10 +/- 4 versus 20 +/- 2 bursts/min; P = 0.026) were lower in normal than in borderline hypertensive men. CONCLUSIONS: At rest, discharge to muscle sympathetic nerves is increased in young borderline hypertensive men; and blood pressure and sympathetic nerve activity are decreased after exercise in borderline hypertensive but not normotensive men. These observations suggest that the depressor response to prolonged rhythmic exercise in young men with borderline hypertension may be due in part to transient suppression of augmented central sympathetic outflow.     

Effects of bromocriptine on catecholamine metabolism in subjects with borderline arterial hypertension

Effects of bromocriptine on hemodynamics and catecholamine exchange were evaluated in patients with borderline arterial hypertension with respect to their family history. The agent was shown to be able to bring down blood pressure and decrease plasma catecholamine levels. With this, platelet monoamine oxidase activity was increased in persons with a family history of hypertensive disease.     

The effect of sodium and potassium loading on urinary kallikrein-like activity in young patients with borderline hypertension

We studied the effects of a potassium supplement on urinary kallikrein excretion in a setting of high sodium intake after sodium deprivation with diuretics in young patients with borderline hypertension. Eleven patients, who took the potassium supplementation during the high sodium diet period, showed lower increments in mean blood pressure with salt loading than 12 patients without the potassium supplementation. In the non-potassium-supplemented patients, urinary kallikrein was increased significantly when plasma renin activity (PRA), plasma aldosterone concentration (PAC), and urinary aldosterone were increased during the diuretic treatment. It was decreased significantly when the other hormones were decreased during the sodium load. During the high sodium diet period, PRA, PAC and urinary aldosterone were greater in the potassium-supplemented patients than in the non-potassium-supplemented ones, but urinary kallikrein excretion was not higher when potassium was supplemented. Thus, the present results did not support the theory that the kallikrein-kinin system may be involved in the natriuretic and antihypertensive effects of potassium. In addition, these finding suggest that some kallikrein-modulating factor(s) may counteract the increased urinary kallikrein excretion with the augmented renin-angiotensin-aldosterone system during salt loading with potassium supplementation.     

Interrelation of cardiac and vascular structure in young men with borderline hypertension

It is not established whether left ventricular hypertrophy andstructural vascular changes are primary phenomena or secondaryconsequences of raised blood pressure. In this study we investigated54 borderline hypertensive men (BH) (SBP 140–160 mmHgand/or DBP 84–95 mmHg) and 20 normotensive men (NC) (SBP110–130 mmHg and DBP 60–80 mmHg), recruited froman unbiased population sample (age 20 ± 2 years). Bloodpressure (BP) levels were confirmed by i.a. BP recordings. Leftventricular mass (LVM) was determined with M-mode echocardiographyand minimal vascular resistance (R_min) was calculated from theblood flow in the calf and forearm after maximal ischaemic work.Central haemodynamics were assessed by intra-arterial bloodpressure recordings and cardiac output determinations by thedye dilution technique. In the BH group, LVM and R_min were stronglycorrelated to body size, especially weight and body surfacearea. However, LVM and R_min were only weakly correlated to bloodpressure. In the normokinetic BH subgroup (NBH) (n = 38) minimalforearm vascular resistance was significantly higher than inthe hyperkinetic BH individuals (HBH) (n = 16), indicating thepresence of structural vascular changes in the former. Furthermore,in the NBH group there was a significant correlation betweenLVM and R_min both in the calf (r = 0.490 P = 0002) and in theforearm (r = 0.520 P = 0.001). This association remained aftercorrection for body size. No such correlation was seen in theHBH subgroup or in the NC group. The present study does givelong-reaching conclusions as regards the aetiological factorsunderlying the cardiovascular remodelling. However, our datashow that (1) cardiovascular changes appear early in the courseof blood pressure elevation, (2) the cardiac and vascular changesdevelop in parallel, and (3) structural remodelling is not solelyexplained by the degree of blood pressure elevation since bloodpressure was similar in the two BH subgroups. Thus, other factorsthan blood pressure appear to be important determinants of structuraladaptation in mildly hypertensive states.     

Early impairment of coronary flow reserve in young men with borderline hypertension

Objectives. The purpose of this study was to investigate whether functional abnormalities in coronary vasomotion are present in young healthy asymptomatic men fulfilling the World Health Organization (WHO) criteria for borderline hypertension.Background. Previous studies have reported reduced coronary flow reserve in middle-aged subjects with sustained hypertension and hypertension-induced microvascular heart disease or left ventricular hypertrophy.Methods. Myocardial blood flow was measured at baseline and during dipyridamole-induced hyperemia by means of positron emission tomography and oxygen-15–labeled water in asymptomatic young men with borderline hypertension (group 1: n = 16, mean ± SD age 37 ± 4 years, 24-h ambulatory blood pressure 135 ± 10/81 ± 9 mm Hg) and matched healthy control subjects (group 2: n = 19, age 35 ± 3 years, 24-h ambulatory blood pressure 119 ± 8/69 ± 8 mm Hg, p < 0.001). Left ventricular (LV) mass, dimensions and function were measured by echocardiography.Results. LV mass, dimensions and diastolic function were similar in the study groups. Baseline myocardial blood flow was similar (0.83 ± 0.21 vs. 0.80 ± 0.22 ml/g per min, group 1 vs. group 2, respectively, p = NS), and a significant increase in flow was detected after dipyridamole infusion (0.56 mg/kg body weight in 4 min intravenously) in both groups. However, the flow response to dipyridamole was significantly lower in group 1, leading to lower hyperemic flow in group 1 than in group 2 (2.85 ± 1.20 vs. 3.80 ± 1.44 ml/g per min, respectively). Consequently, the coronary flow response was lower in hypertensive than in normotensive men (3.46 ± 1.23 vs. 4.99 ± 2.5 ml/g per min, group 1 vs. group 2, respectively, p < 0.05).Conclusions. These results demonstrate reduced coronary reactivity present in young asymptomatic men with borderline hypertension and no signs of hypertension-induced angina or left ventricular hypertrophy. Because baseline basal myocardial blood flow was unchanged, the reduction in coronary flow reserve depends on an impaired maximal vasodilator capacity.     

Attenuated vasodilator responses to Mg2+ in young patients with borderline hypertension

Limb vascular responses to magnesium (Mg2+) and potassium (K+) ions were studied in 19 young patients with borderline hypertension (BHT) and compared with those of 22 age-matched normotensive subjects (NT) by measuring the forearm blood flow response to intra-arterial infusion of magnesium sulfate and potassium chloride using venous occlusion plethysmography. Percent decrements of forearm vascular resistance with Mg2+ infusions were significantly less in BHT subjects than in NT (-37.2 +/- 4.2% versus -53.0 +/- 2.0%, p less than 0.05, during the infusion of 0.1 meq Mg2+/min, and -52.2 +/- 4.3% versus -65.6 +/- 1.5%, p less than 0.05, during the infusion of 0.2 meq Mg2+/min). Moreover, the relation of the magnitude of Mg2+ response to initial vascular resistance in six of 10 BHT subjects lies above the 95% confidence interval for predicted values calculated for response points in 11 NT subjects, suggesting attenuated vasodilator responses of Mg2+ in a significant proportion of BHT subjects. In contrast, the response points to K+ in eight of nine BHT subjects fall within the 95% confidence interval, suggesting normal vasodilator responses to K+ in the majority of BHT subjects. Furthermore, the effect of small increments in local serum calcium concentrations on Mg2(+)- and K(+)-induced vasodilation was studied in normal volunteers. Isosmolar CaCl2 solution infused into the same brachial artery at a rate of 0.09 meq/min severely blunted the vasodilating actions of Mg2+ (-30.1 +/- 6.5% versus -65.8 +/- 3.2%, p less than 0.01, during the infusion of 0.2 meq Mg2+/min) but did not affect those of K+ (-63.1 +/- 3.1% versus -55.9 +/- 3.8%, NS, during the infusion of 0.154 meq K+/min). It appears that Mg2(+)-induced vasodilation should be due to the antagonistic action of Mg2+ to calcium, but K(+)-induced vasodilation might not be directly related to calcium movement. Thus, these attenuated responses to Mg2+ but normal responses to K+ in BHT subjects may indicate an underlying defect in vascular Mg2+ metabolism, which ultimately may be related to the alterations in calcium handling by plasma membranes rather than to the abnormalities of membrane Na(+)-K+ pump activity.     

86Rubidium uptake in mononuclear leucocytes from young subjects at increased risk of developing essential hypertension

This study was designed to assess any changes in mononuclear leucocytes from young men at increased risk of developing essential hypertension and to determine whether any changes found were associated with borderline hypertension and/or heredity. To this end we used mononuclear leucocytes as a cellular model for in vitro measurement of total 86rubidium uptake to give an index of sodium-potassium pump activity. Four groups of subjects were evaluated, 28 normotensive and 20 borderline hypertensive offspring of hypertensives, and 12 borderline hypertensives and 28 normotensives with normotensive parents. 86Rubidium uptake was significantly increased in the borderline hypertensive subjects, especially in the borderline hypertensive offspring of hypertensive patients. Our results indicate that the sodium-potassium pump is activated in mononuclear leucocytes from borderline hypertensives, and especially in those borderline hypertensives with at least one hypertensive parent. The latter group was also the group at greatest risk of developing essential hypertension.