Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension

BACKGROUND. Endothelium regulates vascular tone by influencing the contractile activity of vascular smooth muscle. This regulatory effect of the endothelium on blood vessels has been shown to be impaired in atherosclerotic arteries in humans and animals and in animal models of hypertension. METHODS. To determine whether patients with essential hypertension have an endothelium-dependent abnormality in vascular relaxation, we studied the response of the forearm vasculature to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct dilator of smooth muscle) in 18 hypertensive patients (mean age [+/- SD], 50.7 +/- 10 years; 10 men and 8 women) two weeks after the withdrawal of antihypertensive medications and in 18 normal controls (mean age, 49.9 +/- 9; 9 men and 9 women). The drugs were infused at increasing concentrations into the brachial artery, and the response in forearm blood flow was measured by strain-gauge plethysmography. RESULTS. The basal forearm blood flow was similar in the patients and controls (mean +/- SD, 3.4 +/- 1.3 and 3.7 +/- 0.8 ml per minute per 100 ml of forearm tissue, respectively; P not significant). The responses of blood flow and vascular resistance to acetylcholine were significantly reduced in the hypertensive patients (P less than 0.0001); maximal forearm flow was 9.1 +/- 5 ml per minute per 100 ml in the patients and 20.0 +/- 8 ml per minute per 100 ml in the controls (P less than 0.0002). However, there were no significant differences between groups in the responses of blood flow and vascular resistance to sodium nitroprusside. Because the vasodilator effect of acetylcholine might also be due to presynaptic inhibition of the release of norepinephrine by adrenergic nerve terminals, the effect of acetylcholine was assessed during phentolamine-induced alpha-adrenergic blockade. Under these conditions, it was also evident that the responses to acetylcholine were significantly blunted in the hypertensive patients (P less than 0.03). CONCLUSIONS. Endothelium-mediated vasodilation is impaired in patients with essential hypertension. This defect may play an important part in the functional abnormalities of resistance vessels that are observed in hypertensive patients.     

Stress management training and relaxation imagery in the treatment of essential hypertension

The present study compared the effectiveness of three procedures in the treatment of 34 individuals with essential hypertension: (1) stress management training plus relaxation imagery, which consisted of an adaptation of existing stress management techniques in conjunction with extensive relaxation training using relaxation imagery; (2) relaxation imagery alone; and (3) weekly blood pressure checks. The relaxation imagery technique involved visualization of a relaxing image along with concentration on suggestions of relaxation, heaviness, and warmth. Treatment was individualized and lasted 8 weeks. Results indicated stress management plus relaxation imagery and relaxation imagery alone were significantly more effective than blood pressure checks in reducing systolic and diastolic blood pressures during treatment and in maintaining diastolic blood pressure reductions during follow-up. However, no significant differences were found between the two treatment procedures. Clinical implications of these findings are discussed.     

Home relaxation techniques for essential hypertension

A 10-week relaxation treatment focused on home practice and self-monitoring of blood pressure for the purpose of lowering blood pressure in patients with essential hypertension. Comparisons were made among relaxation (n = 13), relaxation in combination with electromyographic biofeedback (n = 14), and a control condition in which patients simply monitored their blood pressure (n = 14). These three groups of patients, all of which received antihypertensive medication, were compared with a fourth group that practiced relaxation without drug therapy (n = 17). Relaxation and relaxation/biofeedback were equally effective in reducing blood pressure recorded at home in the morning and evening and produced greater decreases than in the control group. Relaxation without drugs, although somewhat more effective than self-monitoring, did not reduce blood pressure as much as the two conditions in which medication was combined with relaxation. Although reductions over the course of treatment were noted in blood pressure recorded in the laboratory, the four treatment conditions did not differ significantly from one another.     

Predicting treatment outcome to progressive relaxation training in essential hypertensive patients

Nineteen borderline essential hypertensive patients participated in (a) a pretreatment assessment of sympathetic nervous system activity (SNS), (b) a progressive muscle relaxation training program, and (c) a posttreatment assessment of SNS functioning. During both pre- and posttreatment assessments, each subject participated in a laboratory session during which cardiovascular responses to two behavioral challenges were measured, a 24-hr urine collection for catecholamine analysis and the completion of relevant self-report questionnaires. Results revealed that subjects who improved the most with relaxation training (showed the greatest reduction in blood pressure) were individuals who, at pretreatment, (a) were less reactive to laboratory challenges, (b) possessed lower levels of resting epinephrine, and (c) scored lower on measures of trait anger and higher on assertiveness. Posttreatment assessment results showed that relaxation training did not affect cardiovascular reactivity to laboratory tasks or self-report of anger and assertion.Funding for this study was made available through a West Virginia University Senate Research Grant (87-824).     

Effects of aldosterone on intralymphocytic sodium and potassium in patients with essential hypertension

Summary In vitro binding of aldosterone to mineralocorticoid receptors on human mononuclear leukocytes (HML) and its effects on the intracellular sodium and potassium concentrations of HML have already been described. In the present paper this easily accessible human cell model was investigated in 13 patients with essential hypertension. In only four patients sodium in HML without incubation was elevated compared with the range for normal persons. A decrease of intracellular sodium or potassium occurred during incubation without aldosterone (P<0.02). The addition of 1.4 nM aldosterone did not prevent this loss of electrolytes as observed in normal persons. Plasma renin activity and aldosterone were not correlated with the electrolyte response and were within the normal limits. The number of mineralocorticoid receptors/cell were within or close to the normal range (n=9). The independence of intracellular electrolytes from aldosterone despite a normal number of mineralocorticoid receptors may reflect an impairment of the mineralocorticoid effector mechanism in the HML of patients with essential hypertension.Abbreviations HML human mononuclear leukocytes - HEPES N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid - Tris Tris(hydroxymethyl)aminomethane     

Meditation training and essential hypertension: A methodological study

Meditation training appears to be a promising psychological approach to the control of hypertension. However, most studies to date have had serious deficiencies. This study attempted to correct many of these deficiencies. Forty-one unmedicated hypertensives referred by general practitioners were randomly allocated to three groups. The treatment group (SRELAX) underwent training procedures based on Transcendental Meditation; a placebo control group (NSRELAX) underwent identical training but without a mantra. Both procedures were compared with a no-treatment control group. The results showed modest reductions in blood pressure in both SRELAX and NSRELAX groups, compared with the no-treatment controls, with diastolic percentage reductions reaching significance (p<0.05). There was considerable subject variation in response, with overall a mean decline in diastolic blood pressure of 8–10% on 3-month follow-up. Possible indicators to predict the response of subjects are considered and reasons for the similarity in the effectiveness of the SRELAX and NSRELAX conditions are discussed.This research was funded by a grant from the Auckland Medical Research Foundation.     

Anger management training with mild essential hypertensive patients

Casual blood pressures and measures of cardiovascular and behavioral reactions to neutral and confrontive interactions were obtained from 13 essential hypertensive patients who received training in anger management and 9 no-treatment control patients. At pre- and posttraining, heart rate (HR) and blood pressure (BP) were measured (a) at rest and (b) during role-play interactions consisting of neutral and confrontation scenes. Behavioral responses were also coded for each interaction. For treatment subjects, a 6-week program in anger management was conducted, which included relaxation training, self-statement modification, and role-play assertiveness training. Treatment subjects exhibited significantly lower casual DBPs at posttraining (M=90.2 mm Hg) than control subjects (M=95.7 mm Hg). Posttreatment casual SBPs for treatment and control subjects were not significantly different. Treatment subjects exhibited significantly more assertive skill and lesser DBP reactivity at posttreatment than their control counterparts during the confrontive interaction but not during the neutral role-play interaction.     

Ventilatory responses in patients with essential hypertension.

We investigated the ventilatory responses to hypoxia and hypercapnia in patients with essential hypertension (HT) as compared with healthy subjects (NV). Further, to evaluate the contribution of the peripheral chemoreceptors to ventilatory response, we used a withdrawal test. Hypoxic ventilatory drive (HVR) was measured as the parameter A denoting the shape of VI (inspiratory minute ventilation)-PETO2 (end-tidal PO2) curve which was calculated by the empirical equation: VI = V0 + A/(PETO2-32). Hypercapnic ventilatory drive (HCVR) was measured as the parameter S denoting the shape of the VI-PETCO2 (end-tidal PCO2) relation which was calculated by the empirical equation: VI = S(PETCO2-B). There were no significant differences in the parameters of HVR and HCVR between NV and HT. A positive correlation between A/BSA and S/BSA was found to be significant in NV (r = 0.873, p less than 0.05). Conversely, there was no significant correlation between A/BSA and S/BSA (r = 0.547) in HT. On the other hand, the withdrawal responses (delta VI/BSA and % delta VI:delta VI/VI x 100%) were obtained from the magnitude of depression in ventilation caused by two breaths of O2 in hypoxic hypercapnia. In the withdrawal responses, delta VI/BSA and % delta VI in HT were significantly higher than those in NV. A/BSA significantly correlated with delta VI/BSA (NV, r = 0.684, p less than 0.05; HT, r = 0.648, p less than 0.05) in both NV and HT. However, delta VI/BSA in HT tended to be higher than that in NV, under the same value of A/BSA. These results suggested that the peripheral chemoreceptor activity was augmented in HT.     

Blood pressure variability and stress management training for essential hypertension

The purpose of this study was to determine whether stress management training reduces blood pressure (BP) variability in hypertensive patients. Previous literature suggests that cardiovascular risk is not only a function of BP levels, but also of BP variability, and this partially depends on changes induced by the stress of everyday life. The authors reanalyzed data from a previous study of 43 male patients with essential hypertension who were randomly assigned to 2 groups (stress management training and waiting list). Patients in the stress management group lowered their self-measured BP variability significantly from pretreatment to the 4-month follow-up examination, showing a mean reduction of 2.6/1.5 mm Hg in the standard deviation of systolic/diastolic BP (SBP/DBP), and a mean decrease of 1.84/1.59% in the coefficient of variation of SBP/DBP. For SBP, these reductions were significantly greater than those showed by the control group. These results suggest that stress management training is effective in reducing day-to-day BP variability, providing an additional reduction in cardiovascular risk for hypertensive patients.     

Effects of the new angiotensin-converting enzyme inhibitor,ramipril, in patients with essential hypertension

Summary The antihypertensive and hormonal effects of the new angiotensin-converting enzyme (ACE) inhibitor, ramipril, were assessed by means of a single-blind trial in ten unselected patients with mild-to-moderate essential hypertension. After a 2-week period on placebo, 5 mg ramipril was administered once daily for 2 weeks. Blood pressure returned to normal in five patients and decreased in the remaining patients, without significant changes in heart rate or orthostatic hypotension. A fall in blood pressure was apparent within 1–2 h of the first dose; the maximum decrease was reached at 4–6 h and a fall in pressure was still detectable after 24 h. At 24 h post dose angiotensin-converting enzyme activity was suppressed to 40% of the baseline. Blood pressures for the 10 h interval post dosing showed smooth through-the-day control with minimal peak/trough difference in lowering effect. The magnitude of the blood pressure decrement achieved with the inhibitor did not correlate with baseline renin levels or the rise in renin following treatment. No side-effects were noted during the 2-week observation period. The study demonstrates that ramipril, given in a once-daily regimen over a period of 2 weeks, is well tolerated and provides smooth and effective blood pressure control throughout the 24-h interval between doses.Abbreviations ACE angiotensin converting enzyme - PRA plasma renin activity     

Apo E polymorphism among Egyptian patients with essential hypertension

Hypertension (HTN) is a chronic condition of concern due to its role in the causation of coronary artery disease (CAD), stroke, and other vascular complications. Essential hypertension (EH) is a multifactorial disorder arising from the influence of several susceptibility genes and environmental stimuli. Apolipoprotein E (Apo E) plays an essential role in clearance of chylomicron remnants and very low-density lipoproteins (VLDL). Apo E gene has three alleles (E2, E3, and E4) that give rise to six different genotypes. A significant association of E4 allele has been observed with HTN in addition to the other well-known risk factors and positive family history. Carriers of E4 allele form a higher risk group showing greater susceptibility to CAD. These observations emphasize the need of genotyping Apo E in patients with EH as an important molecular tool in personalized medicine. The aim of this work was to study the association between Apo E gene polymorphism and EH in Egyptian patients as well as correlating different Apo E genotypes with serum lipids. The study was conducted on 50 patients with EH and 50 age-matched controls. DNA analysis was performed using polymerase chain reaction restriction fragment length polymorphism. The E3/E3 genotype was found in 85.42 % of patients, compared to 80 % in controls. E3/E4 (8.33 %) and E2/E3 (6.25 %) were lower in patients compared to controls 12 and 8 %, respectively. E4/E4 and E2/E2 genotypes were only found in two patients (4 %). Total cholesterol and low-density lipoprotein were significantly higher in E3/E4 as compared to E3/E3 and E2/E3. However, there was no significant difference in triglyceride, high-density lipoprotein, and VLDL.     

Efficiency and safety of ACE-inhibiting imidapril in patients with essential hypertension

In a survey including 2224 patients with essential hypertension we investigated efficacy and tolerability of the new ACE-inhibitor Imidapril. Mean blood pressure at baseline was 172 +/- 19/98 +/- 10 mmHg. Treatment with Imidapril 5-20 mg once daily caused a decrease in BP by 21 +/- 17/11 +/- 10 mmHg (p < 0.01/0.01). Systolic BP was reduced by > 15 mmHg in 71% diastolic BP by > 10 mmHg in 64% of patients. 29% of patients achieved the treatment goal of a blood pressure < or = 140/90 within an average of 26 days. Imidapril decreased pulse-pressure (one of the most important risk markers in hypertension) by 18% (74 +/- 17 to 61 +/- 11 mmHg, p < 0.01). ACE-inhibitor related adverse effects (cough, vertigo, headache, pruritus, tachycardia, orthostatic dysregulation or nausea) were observed in 38 patients (< 2%). Efficacy of treatment was graded by the physician in charge of the patient care by means of a questionnaire. Gradings were excellent or good in 96% of patients, moderate in 3% and poor in < 1%. In summary, the effects of Imidapril on blood pressure were comparable to those of other ACE-inhibitors. However, the frequency of adverse effects was low and similar to that of angiotensin-II-antagonists.     

Beta-adrenergic blockade in diuretic-treated patients with essential hypertension.

The influence of beta-adrenergic blockade (160 mg per day of propranolol for four weeks) on plasma renin activity, plasma volume, and arterial pressure was explored in 20 patients with essential hypertension with hyper-reninemia from long-term diuretic therapy. In 15 of these patients renin activity remained elevated (range, 3.1 to 23.0 ng per milliliter). Plasma volume was unchanged in eight, increased in 11 and reduced in one. In 17 subjects mean arterial pressure decreased by more than 10 mm Hg, but these impressive reductions could not be explained by quantitative changes in either renin activity (r equals 0.1) or plasma volume (r equals 0.1). These data suggest that suppression of plasma renin activity by beta-adrenergic blockade is not attainable during diuretic therapy and is not the major factor responsible for the antihypertensive action of propranolol.     

A long-term follow-up of patients with essential hypertension treated with captopril

Seventy-four patients from four short-term studies of captopril in mild-moderate essential hypertension continued in a cooperative long-term efficacy and tolerance program. The duration of observation is 2- greater than 4 years, the total treatment time being 2434 months. No development of resistance to therapy was observed. The total daily dose of captopril has been gradually decreased and in 20 patients changed from t.i.d. to b.i.d. regime. The drug has been well tolerated and only few and mild side-effects have been observed after the initial titration period. The drop-outs (n = 19) were mostly due to non-medical causes (n = 14). Except for one case of proteinuria, no laboratory abnormalities were detected and there were no signs of long-term toxicity.     

Biofeedback of baroreflex sensitivity in patients with mild essential hypertension

An attempt was made to reduce blood pressure by increasing the baroreflex sensitivity (BRS) via biofeedback. Six patients with mild essential hypertension and 5 normotensive participants were studied during 8 biofeedback sessions. Each session consisted of 5 trials, 5 min each. The first and the last trials served as baselines of heart rate, blood pressure, respiration, and BRS. During the3 middle trials the BRS was calculated online using the sequencing technique. The resulting value was used as a visual analogue feedback signal. Participants were asked to increase BRS. The mean BRS was 8.3 [ms/mmHg] for the hypertensive patients and 12.2 [ms/mmHg] for the normotensive participants. During biofeedback trials as well as across sessions neither the hypertensive nor the normotensive group showed a statistically significant increase of BRS, only heart rate variability increased significantly. Contrary to expectation blood pressure increased in both groups. One hypertensive subject made significant progress during the training by performing valsalva maneuvers. The data show that BRS is reduced in hypertensive subjects. The increase of the heart rate variability could be a sign of the activation of the baroreflex although the BRS itself did not increase. Despite the successful technical and organizational im plementation of this biofeedback approach, it was not effective to systematically reduce blood pressure. A further development in the direction of guiding the patient to use the valsalva breathing pattern and/or a prolonged duration of the biofeedback training might be promising.     

Effects of body-mind training and relaxation stretching on persons with chronic toxic encephalopathy

The purpose of this project was to investigate the psychological and physical effects of training of body awareness and slow stretching on persons with chronic toxic encephalopathy (CTE). In the present study, a method of self-regulation, a body-mind training, is presented. The body-mind training used was a guided relaxation technique combined with meditative stretching. The techniques are introduced and the psychological and physiological effects of the training is presented. Eight subjects with CTE, 48.5 years, were trained for 8 weeks. Outcome measures were percentage alpha brain waves (alpha%), electromyography (EMG) on the frontalis muscle, state-trait anxiety (STAI), creativity (RAT), and mood measured as anxiousness, humour and mental fatigue. The mean alpha% increased 52% during the training period (P < 0.01), and the EMG decreased 31% (P < 0.001. State anxiety decreased 22% during the training period (P < 0.01), but no changes were observed in trait anxiety and in the creativity score. The level of anxiousness and fatigue before a training session decreased during the training period. In conclusion, the body-mind training resulted in an improved ability for physical and mental relaxation as indicated from the lower EMG, the higher alpha% and the decrease in state anxiety.     

Capillary changes in skeletal muscle of patients with essential hypertension

Arterial hypertension produces changes along the vascular tree. However, there are few reports on its effect on human muscle capillaries. This study demonstrates the effects of essential hypertension on the capillaries of human quadriceps muscle. Muscle biopsy was taken from quadriceps femoris in eight men with recent diagnosis of essential hypertension, without treatment. Biopsies were also taken from eight normotensive men and were used as controls. Fiber types were classified by ATPase reaction, capillaries counted in alpha-amylase-PAS stained sections and ultrastructure studied by conventional methods of transmission electron microscopy. No changes were found in capillaries or muscle fiber types by histochemical methods. However, electron microscopy revealed abnormal capillaries with endothelial cells infoldings into the lumen, as well as occluded or degenerated capillaries. In some cases the endothelial cell area covered by pericytes was increased. Basement membrane of capillaries was frequently increased in width, sometimes irregularly, and in other instances it was reduplicated. In transversely sectioned capillaries lumen diameter was reduced and wall thickness was increased, although total diameter was unchanged. In hypertensive patients the finding of some degenerated capillaries adjacent to muscle fibers could be interpreted as the beginning of a process of rarefaction. Some capillaries showed morphological changes, and the ratio wall thickness/lumen was increased.     

Perceived interpersonal attitudes and psychiatric complaints in patients with essential hypertension

The association between perceived interpersonal attitudes and psychiatric complaints in a group to hypertensives (N = 37) was evaluated. The Influential Relationships Questionnaire (IRQ), which measures perceived care, overprotection, and criticism, was administered to all patients. Hypertensives with psychiatric complaints (n = 14) were not different in terms of age, gender, obesity, smoking, alcohol intake, occupational stress, drug treatment, and baseline systolic and diastolic blood pressures compared to hypertensives without psychiatric complaints. They were, however, different in perceiving their social environment. Hypertensives with psychiatric complaints perceived their social environment as less caring, more overprotective, and more critical. Finally, patients without psychiatric complaints showed better outcome in terms of baseline vs. follow-up measures of systolic and diastolic blood pressures than did patients without psychiatric complaints.