Resting blood pressure and cardiovascular response to sympathetic stimulation in adolescents.

The prevalence of significant hypertension in childhood may be higher than expected. We have measured sitting blood pressure in 168 11-yr-old children attending a pre-high school in the Neapolitan area on four occasions over a 3-month period. We have also measured blood pressure and heart rate during a mental arithmetic test and during isometric exercise. Prevalence of significant hypertension (diastolic blood pressure 82-90 mmHg) was 13% at the first visit and decreased to 6.5% at the last visit; prevalence of severe hypertension (diastolic blood pressure greater than or equal to 90 mmHg) decreased from 5.4% to 1.2% from the 1st to the 4th visit. No sex-related difference was observed. A more frequently positive family history of hypertension (50% vs 30% in the fifth and first quintile of blood pressure, respectively) and higher body weight (body mass index = 21.4 vs 19.3 kg/m2) were found in children in the 5th quintile of blood pressure distribution. Blood pressure increased during mental arithmetic by 10/13% of the resting values in the first quintile and by 6/11% in the last one during mental test; during handgrip the increase was of 20/37% and 24/46%, respectively: differences between quintiles did not reach statistical significance. These data show that about 8% of a Neapolitan sample of school population have high blood pressure levels, while no difference in vascular reactivity to sympathetic stimulation was detected in children with higher blood pressure.     

Response of blood vessels to sympathetic nerve stimulation.

The frequency response curves (FRC) of isolated blood vessels differ from each other not only in their initial slopes, but in their maxima, and their intercept on the frequency axis. Within the physiological range, there is a linear relation between response and frequency. The FRC of most vessels with junctional innervation are similar, varying only somewhat with innervation density. Other factors found to influence the FRC are: variation in innervation distribution, in the extent of myogenic propragation, and large differences in the sensitivity of the alpha-adrenergic receptor. The effectiveness of the transmitter increases with frequency rise. The maximum effective radius of the transmitter released from one varicosity is only several microns. In vessels with light to moderate innervation density at low frequencies, there is probably little overlap of transmitter effect from adjacent varicosities even at the outermost layers of smooth muscle cells. There is a disparity between neurogenic response and that which might be expected from the direct action of the transmitter. It is proposed that a local limited myogenic extension of excitation may extend the local action of a quantum of transmitter.     

Effects of morphine on the peripheral vascular response to sympathetic stimulation

The mechanism of action of morphine in acute pulmonary edema has not been clear. Since pulmonary edema is associated with a marked increase in sympathetic nervous system activity, it is possible that the efficacy of morphine in that condition is related to an attenuation of vascular responses to sympathetic stimuli. We examined the effects of morphine on the responses of systemic resistance and capacitance vessels to adrenergic stimulation.     

Enhanced blood pressure response to mineralocorticoid stimulation in normotensive members of hypertensive families.

Currently normotensive offspring of essential hypertensive parents often have disturbances in blood pressure (BP) regulation such as abnormalities in electrolyte homoeostasis, increased salt-sensitivity and/or impaired renal Na(+)-excretion. Whether an altered reactivity to mineralocorticoids may also play a role is presently unknown. Therefore, we investigated BP (recorded during 24 h), plasma atrial natriuretic factor (ANF), cyclic guanosine monophosphate (cGMP), aldosterone (PA) and renin activity (PRA), 24-h urine electrolyte and cGMP excretions measured on 4 consecutive days, as well as other variables, after 1 week on placebo and after 3 weeks of 9 alpha-fludrocortisone-acetate (9 alpha F) administration, 0.6 mg/d in 12 normotensive sons of essential hypertensive parents (SEH) and 12 body-mass-index- and age-matched (25 +/- 1[+/-SEM]yr) sons of normotensive parents (SN). On placebo, the 2 groups did not differ significantly in average 24 h BP (mean BP 95 +/- 2 vs 95 +/- 2 mmHg), plasma-ANF (40 +/- 7 vs 30 +5 pg/ml), cGMP (6 +/- 0.4 vs 6 +/- 0.5 nmol/l), PRA (1.3 +/- 0.1 vs 1.6 +/- 0.2 ng/ml/h), PA (9 +/- 0.5 vs 10 +/- 0.9 ng/dl), hematocrit (44 +/- 0.7 vs 44 +/- 0.4%) and 96-h urinary-Na+ (mean 205 +/- 13 vs 195 +/- 16 mmol/d), -K+ (69 +/- 6 vs 78 +/- 7 mmol/d) or -cGMP (461 +/- 35 vs 483 +/- 32 nmol/d). 9 alpha F significantly increased BP in SEH (p < 0.005) but not SN (107 +/- 2 vs 100 +/- 2 mmHg, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Physiological and catecholamine response to sympathetic stimulation in turner syndrome

OBJECTIVE: Women with Turner syndrome have increased heart rate and high blood pressure (BP), and have been described as having high tolerance for emotional stress. We hypothesized that women with Turner syndrome have reduced catecholaminergic and physiological response to sympathetic stimulation, and that changes in BP and heart rate are related to their catecholamine response to sympathetic stimulation. DESIGN AND PATIENTS: Ten young women with Turner syndrome, age 17-34 years were the subjects of this study. Their response to sympathetic stimulation was compared to a group of 10 age-matched healthy women. MEASUREMENTS: After a period of 30 min resting, subjects and controls were subjected to an escalating series of sympathetic stimulation: orthostatic, cold pressor and exercise, and their plasma catecholamines and haemodynamic response were monitored and compared to resting levels. RESULTS: Resting heart rate was higher in Turner syndrome patients at 83 +/- 9 beats per min (bpm, mean +/- SD), as compared to controls (74 +/- 10 bpm, P < 0.05). Their supine BP was also higher at 122 +/- 9/84 +/- 6 vs. 106 +/- 11/70 +/- 9 mmHg (P < 0.02/< 0.02). The corresponding resting norepinephrine, but not epinephrine, was higher in Turner syndrome patients (2.54 +/- 1.09 nmol/l) as compared to controls (1.69 +/- 0.55 nmol/l, P < 0.02). In response to orthostatic stimulation and cold pressor test the systolic, but not the diastolic BP or heart rate, increased in Turner syndrome patients but not in the control group (P < 0.01). The change in blood catecholamine levels was comparable in both groups. Their physiological response to exercise was normal. Yet, the exercise-induced surge of norepinephrine and epinephrine in Turner syndrome patients was lower (P < 0.02). CONCLUSIONS: Turner syndrome is associated with dysregulation of the sympathetic nervous system (SNS), leading to tachycardia and high BP, increased resting norepinephrine levels, and a greater tolerance of the cathecholamine response to exercise.     

Body weight and cardiovascular response to sympathetic stimulation in childhood

The possible relationship between cardiovascular response to adrenergic stimulation and body weight has been studied in 166 eleven-year-old students (103 male, 63 female). Resting blood pressure (BP) by random-zero machine, heart rate (HR) and body weight (BMI) were measured four times in the school at 3-week intervals. On the third visit a mental arithmetic stress was carried out and a 24 h urine specimen was collected for the measurements of catecholamine excretion. On the fourth visit students carried out an isometric exercise (handgrip). Girls were more frequently found in the last quintiles of BMI (10/33 in the first vs 19/33 in the fifth). This might be due to a more advanced sexual maturation. BP at rest significantly increased with body weight (from 105/81 +/- 11/13 mmHg in the first to 119/87 +/- 10/12 in the fifth quintile). In each quintile no sex-related difference was observed in BP or HR. A marked cardiovascular response was observed during both tests without significant difference among quintiles. The 24 h urinary excretion of total catecholamines slightly increased with body weight (from 26.2 +/- 11 micrograms/24 h in the first to 34.5 +/- 19.5 micrograms/24 h in the fifth quintile). These data in a population of 11-year-old students therefore support the hypothesis that although BP at rest is influenced by BMI, the cardiovascular response to adrenergic stimulation is independent of body weight.     

Predicting the blood pressure response to atenolol

The fall in blood pressure in response to atenolol 50 mg per day has been estimated using ambulatory BP and heart rate monitoring during the day in 35 mild to moderate hypertensive patients. The fall in pressure for the group averaged 18.2 +/- 11.3/11.5 +/- 8.3 mmHg. The 95% confidence internals were 14.5-22.0 mmHg systolic and 8.8-14.3 mmHg diastolic with the individual responses in diastolic pressure being related to the pretreatment variability of diastolic pressure (r = 0.65 P less than 0.001) and to the initial heart rate (r = 0.35 P less than 0.05). With atenolol treatment the BP fall is greater in patients with a more unstable BP. Blood pressure reduction is achieved by reducing the level of cardiac activity.     

Role of sympathetic nervous system activity in the blood pressure response to long-term captopril therapy in severely hypertensive patients

Twenty severely hypertensive subjects who did not achieve blood pressure control with combination therapy with a vasodilator, a beta-adrenergic blocking agent and a diuretic received the angiotensin-converting enzyme inhibitor captopril. Marked decreases in blood pressure were observed immediately. Achievement of sustained reductions in blood pressure into the normal range for up to 3 years of follow-up required the addition of a diuretic in all patients and of a beta-adrenergic blocking agent in half. As expected, significant increases in plasma renin activity and decreases in plasma aldosterone were seen initially and sustained throughout the study. Plasma and urinary norepinephrine levels, which were markedly increased before captopril treatment, decreased significantly and remained low for the duration of study. These observations suggest a link between the renal pressor and sympathetic systems which may be involved in the pathophysiology of severe, treatment-resistant hypertension, and suggest that part of the antihypertensive action of captopril may be related to a decrease in sympathetic activity secondary to its interference with the generation of angiotensin II.     

Reproducibility of blood pressure response to hydrochlorothiazide

Few studies have investigated the reproducibility of responses to antihypertensive therapies. The purpose of this study was to assess the reproducibility of the blood pressure response to a thiazide diuretic, a preferred initial treatment for hypertension. Twenty-two subjects who underwent monotherapy with hydrochlorothiazide as part of a study to identify predictors of blood pressure response agreed to undergo the same protocol a second time, 26.6+/-11.8 (range, 4-52) months after their first participation. The mean systolic and diastolic blood pressure responses to hydrochlorothiazide did not differ significantly between the first and second participation (systolic response, -14.2+/-16.4 mm Hg vs. -16.0+/-16.5 mm Hg; diastolic response, -7.1+/-11.8 mm Hg vs. -6.6+/-8.6 mm Hg), and these responses were significantly correlated between the two trials (systolic response, r=0.61 and p<0.01; diastolic response, r=0.64 and p<0.01). However, both the direction and magnitude of responses for individual subjects varied considerably, with the limits of agreement between the first and second participations (i.e., 2 standard deviations above and below the mean difference between responses) ranging from 27.4 mm Hg to -23.8 mm Hg for systolic blood pressure response and from 17.4 mm Hg to -18.4 mm Hg for diastolic blood pressure response. These results show that the average systolic and diastolic blood pressure responses to hydrochlorothiazide for a group of subjects are reproducible; however, the responses for individual subjects are unpredictable.     

Influence of abdominal pressure and sympathetic vasoconstriction on the cardiovascular response to positive end-expiratory pressure.

The role of changes in abdominal pressure and sympathetically mediated vasoconstriction in the cardiovascular response to positive end-expiratory pressure was evaluated in 9 mongrel dogs. When the abdomen was widely opened, the decrease in cardiac output caused by positive end-expiratory pressure was the same as that found during control studies. When the abdomen was tightly bound, cardiac output was higher at any positive end-expiratory pressure than in control state (P less than 0.01), but the percent decrease produced by increasing positive end-expiratory pressure was the same. alpha-Adrenergic blockade with phenoxybenzamine produced a significantly greater decrease in cardiac output at any given positive end-expiratory pressure and thus appeared to inhibit the previously operative peripheral vascular adjustments to positive end-expiratory pressure. The major compensatory mechanism in the cardiovascular response to positive end-expiratory pressure thus appears to be mediated via alpha-adrenergic sympathetic factors.     

Pretreatment plasma renin activity levels correlate with the blood pressure response to telmisartan in essential hypertension

BACKGROUND: Although the therapeutic response to angiotensin II receptor blockers (ARBs) is assumed impaired in patients with low-renin hypertension, data are scarce about the association between levels of plasma renin activity (PRA) before treatment and response of ambulatory blood pressure (ABP) to ARBs in essential hypertension. METHODS: We prospectively studied 11 untreated Japanese patients with essential hypertension (3 women and 8 men, mean age: 50 +/- 9 (mean +/- SD) years). After a 4-week drug-free period, telmisartan 20-40 mg was administered orally once daily for 8 weeks. PRA levels were measured before treatment. The first ABP measurement was performed at the end of the drug-free period and the second measurement at the end of the treatment period with telmisartan. RESULTS: Telmisartan significantly decreased the 24-h ABP by 12 +/- 11 mm Hg systolic (P < 0.01) and 9 +/- 8 mm Hg diastolic (P < 0.01). Reductions in the 24-h systolic and diastolic ABPs were significantly greater in five patients with higher renin levels (> or =0.65 ng/ml/h) than in six patients with lower renin levels (<0.65 ng/ml/h) by 18 mm Hg systolic (P < 0.001) and 11 mm Hg diastolic (P < 0.05). Changes in the 24-h systolic and diastolic ABPs significantly correlated with log PRA before treatment. CONCLUSIONS: The ABP lowering effects of telmisartan were dependent on PRA levels before treatment in patients with essential hypertension. Measurement of PRA levels before treatment is thought to be useful for prediction of the ABP lowering effects of telmisartan.     

Serum cholesterol levels, blood pressure response to stress and incidence of stable hypertension in young subjects with high normal blood pressure

RATIONALE: Elevated serum cholesterol levels are common in patients with high blood pressure (BP) and could contribute to the progression of the hypertensive disease. OBJECTIVE: To determine whether serum cholesterol levels affect the BP response to mental stress (MA) and the development of stable hypertension in young subjects with high normal BP. METHODS: Seventy young (age < 45 years) high normal BP subjects with elevated (> 200 mg/dl, n = 49; HC) or normal (< or = 199 mg/dl, n = 21; NC) serum cholesterol levels, and 20 normotensive normocholesterolaemic (serum cholesterol < 199 mg/dl; C) subjects undergoing standardized mental challenge (mental arithmetic) were followed up for 15 years according to a prospective, longitudinal, cohort study design conducted in an ambulatory setting. The main outcome measure was the evaluation of the 15-year incidence of stable hypertension (diastolic BP > 95 mmHg). RESULTS: After adjustment for age, resting BP, family history of high BP and body mass index at the study entry, high normal BP subjects with HC showed an enhanced BP reactivity to stress and a higher 15-year incidence of stable hypertension compared to high normal BP and NC subjects [relative risk (RR) = 2.1; 95% confidence interval (CI) = 1.7-5.5, P < 0.001] and controls (RR = 3.1; 95% CI = 1.4-5.3, P < 0.001). In a multivariate analysis of data the presence of high cholesterol levels was an independent predictor for the development of hypertension. CONCLUSION: These data suggest that subjects with high normal BP and elevated serum cholesterol might have an exaggerated cardiovascular response to stress and have an increased risk for stable hypertension that can be detected at young age.     

Effect of digitalis on response of the ventricular pacemaker to sympathetic neural stimulation and to isoproterenol

It is established that digitalis antagonizes the chronotropic effect of adrenergic stimulation of the heart, and this finding suggests that the sympathetic nervous system does not play a significant role in ventricular arrhythmias produced by digitalis. However, this antagonism has been established by testing the response of the sinus nodal pacemaker to digitalis and adrenergic stimulation. Since clinically significant digitalis-induced arrhythmias are ventricular in origin, the response of the ventricular pacemaker seems the more critical variable. To test this hypothesis, we applied two types of adrenergic stimulation before and after ouabain administration to anesthetized dogs with complete atrio-ventricular block. Ouabain in a dose of 40 μg/kg caused no significant change in the increase in heart rate produced either by electrical stimulation of postganglionic sympathetic nerves or by isoproterenol administration. In 6 of the 12 dogs ventricular tachycardia developed after digitalis administration at levels of adrenergic stimulation that did not cause arrhythmia before the drug was given. These results indicate that digitalis does not affect the chronotropic response to adrenergic stimulation of ventricular pacemakers. Moreover, the heart exposed to digitalis appears to be sensitized to the arrhythmogenic effects of adrenergic stimuli.