Differences In Blood Pressure Responses Research Articles

Effects of monotherapy with sustained-release verapamil on blood pressure, lipid levels, renal function, diabetic control, and patient well-being in patients with mild to moderate hypertension

The effects of sustained-release (SR) verapamil (Isoptin® SR) monotherapy on blood pressure (BP), lipid levels, renal function, diabetic control, and patient well-being were investigated in an open-label multicenter trial of 507 patients with mild or moderate hypertension. Newly diagnosed and previously treated patients received SR verapamil 240 mg once daily for 6 weeks, with the option of titrating dosage to a maximum of 480 mg/day. Equal numbers of men and women (251 men, 251 women, 5 not reported) with an average age of 60 years were enrolled in the study. The greatest decreases in BP were achieved between baseline and week 2, when (mean ± SD) BP fell from 163 ± 20 mmHg systolic (SBP)/98 ± 9 mmHg diastolic (DBP) to 149 ± 17 mmHg SBP/88 ± 9 mmHg DBP. Blood pressure readings after 6 weeks of treatment were 147 ± 17 mmHg SBP/86 ± 9 mmHg DBP. The mean percentage decrease in BP by week 6 was 9.24% for SBP and 12.21% for DBP. SR verapamil was found to be as efficacious in patients age >64 as in younger patients. No significant difference in BP response was observed when patients were stratified by age. Overall, 85% of patients attained goal BP (ie, DBP ⩽90 mmHg or a ⩾10-mmHg decrease in DBP). Target BP was reached by 80% of patients with mild hypertension at baseline and 87% of those with moderate hypertension. Treatment with SR verapamil had a beneficial effect on lipid levels and patient well-being; no effects on renal function or glycemic control were noted. Side effects were reported by 114 (22.5%) patients; the most commonly reported effect was mild constipation (10.7%). The authors conclude that SR verapamil is a safe and effective drug in the treatment of hypertension.

Weight loss intervention in phase 1 of the Trials of Hypertension Prevention. The TOHP Collaborative Research Group

Phase 1 of the Trials of Hypertension Prevention was a collaborative, randomized controlled clinical trial designed to determine the feasibility and efficacy of selected nonpharmacologic interventions in reducing or preventing an increase in diastolic blood pressure. Participants aged 30 to 54 years who had a high-normal diastolic blood pressure (80 to 89 mm Hg), and were between 115% and 165% of their desirable body weight, were randomly assigned to either an 18-month weight loss intervention (n = 308) or a usual-care control condition (N = 256). Intervention consisted of 14 weekly group meetings followed by monthly maintenance sessions. Intervention participants received training in behavioral self-management technique and were asked to make life-style changes aimed at achieving a moderate reduction in energy intake and an increase in physical activity. The average weight losses in the intervention group at 6, 12, and 18 months of follow-up were 6.5, 5.6, and 4.7 kg for men and 3.7, 2.7, and 1.6 kg for women. The mean (+/- SE) change in diastolic blood pressure for intervention participants compared with controls at termination was -2.8 +/- 0.6 mm Hg for men and -1.1 +/- 0.9 mm Hg for women. For systolic blood pressure, the corresponding change was -3.1 +/- 0.7 mm Hg for men and -2.0 +/- 1.3 mm Hg for women. Blood pressure reductions were greater for those who lost larger amounts of weight. Sex-related differences in blood pressure response were largely due to the smaller amount of weight lost by women, and sex differences in weight loss could be accounted for by differences in baseline body weight. During an 18-month follow-up period, this weight reduction program was shown to be an effective nonpharmacologic intervention for reducing blood pressure in overweight adults with high-normal blood pressure.

Weight Loss Intervention in Phase 1 of the Trials of Hypertension Prevention

<h3>Background:</h3> Phase 1 of the Trials of Hypertension Prevention was a collaborative, randomized controlled clinical trial designed to determine the feasibility and efficacy of selected nonpharmacologic interventions in reducing or preventing an increase in diastolic blood pressure. <h3>Methods:</h3> Participants aged 30 to 54 years who had a high-normal diastolic blood pressure (80 to 89 mm Hg), and were between 115% and 165% of their desirable body weight, were randomly assigned to either an 18-month weight loss intervention (n=308) or a usual-care control condition (N=256). Intervention consisted of 14 weekly group meetings followed by monthly maintenance sessions. Intervention participants received training in behavioral self-management technique and were asked to make life-style changes aimed at achieving a moderate reduction in energy intake and an increase in physical activity. <h3>Results:</h3> The average weight losses in the intervention group at 6, 12, and 18 months of follow-up were 6.5, 5.6, and 4.7 kg for men and 3.7, 2.7, and 1.6 kg for women. The mean (±SE) change in diastolic blood pressure for intervention participants compared with controls at termination was —2.8±0.6 mm Hg for men and —1.1 ±0.9 mm Hg for women. For systolic blood pressure, the corresponding change was —3.1±0.7 mm Hg for men and —2.0±1.3 mm Hg for women. Blood pressure reductions were greater for those who lost larger amounts of weight. Sex-related differences in blood pressure response were largely due to the smaller amount of weight lost by women, and sex differences in weight loss could be accounted for by differences in baseline body weight. <h3>Conclusions:</h3> During an 18-month follow-up period, this weight reduction program was shown to be an effective nonpharmacologic intervention for reducing blood pressure in overweight adults with high-normal blood pressure. (Arch Intern Med. 1993;153:849-858)

Stability of cardiovascular reaction patterns across subjects and situations

The hemodynamic response to sequences of ventricular fibrillation and defibrillation includes an adrenergic component that is important for the maintenance of blood pressure after successful defibrillation. Because calcium channel blocking drugs have antiadrenergic effects, we hypothesized that they might blunt the adrenergic response to defibrillation. Ventricular fibrillation was induced in 35 closed-chest dogs. Each recaived 4 to 7 direct current transthoracic shocks at three energy levels to determine defibrillation energy requirements. Heart rate and blood pressure were recorded. Energy sequences were repeated after 45 minutes of no intervention (control, n = 5) or after 45-minute infusions of diltiazem (0.1 mg/kg/min, n = 10), verapamil (0.1 mg/kg bolus plus 0.01 mg/kg/min, n = 10), or nifedipine (40 μg/min for 3 minutes plus 2 to 20 μg/min adjusted to maintain a 10 mm Hg drop in mean arterial pressure, n = 10). Our results show that the normal post-shock rise in mean arterial pressure was blunted by the calcium channel blockers diltiazem (systolic arterial pressure at 15 and 60 seconds post-shock, pre-drug versus post-drug: 102 ± 9 versus 64 ± 9 mm Hg and 113 ± 10 versus 87 ± 6 mm Hg; p < 0.05) and verapamil (108 ± 9 versus 78 ± 12 mm Hg and 113 ± 7 versus 90 ± 10 mm Hg, p < 0.05). There were no differences in blood pressure responses after nifedipine treatment or no drug. Heart rate responses were not altered by diltiazem or verapamil; after nifedipine administration, post-shock heart rates were slower. After treatment with diltiazem and verapamil there was a modest reduction in percent shock success across all energy levels (diltiazem: 28% ± 7% versus 17% ± 6%, 71% ± 9% versus 52% ± 14%, and 87% ± 13% versus 82% ± 11% at 25 J, 50 J, and 100 J, respectively [ p < 0.05 ]; verapamil: 50% ± 14% versus 15% ± 2%, 64% ± 11% versus 44% ± 14%, and 82% ± 9% versus 72% ± 13%, respectively [ p < 0.05 ]). Nifedipine did not alter shock success rates. This study suggests that calcium channel blocking drugs blunt the adrenergic response to defibrillation.

Event-related potentials elicited by neutral stimuli and emotion-expressing human faces

The hemodynamic response to sequences of ventricular fibrillation and defibrillation includes an adrenergic component that is important for the maintenance of blood pressure after successful defibrillation. Because calcium channel blocking drugs have antiadrenergic effects, we hypothesized that they might blunt the adrenergic response to defibrillation. Ventricular fibrillation was induced in 35 closed-chest dogs. Each recaived 4 to 7 direct current transthoracic shocks at three energy levels to determine defibrillation energy requirements. Heart rate and blood pressure were recorded. Energy sequences were repeated after 45 minutes of no intervention (control, n = 5) or after 45-minute infusions of diltiazem (0.1 mg/kg/min, n = 10), verapamil (0.1 mg/kg bolus plus 0.01 mg/kg/min, n = 10), or nifedipine (40 μg/min for 3 minutes plus 2 to 20 μg/min adjusted to maintain a 10 mm Hg drop in mean arterial pressure, n = 10). Our results show that the normal post-shock rise in mean arterial pressure was blunted by the calcium channel blockers diltiazem (systolic arterial pressure at 15 and 60 seconds post-shock, pre-drug versus post-drug: 102 ± 9 versus 64 ± 9 mm Hg and 113 ± 10 versus 87 ± 6 mm Hg; p < 0.05) and verapamil (108 ± 9 versus 78 ± 12 mm Hg and 113 ± 7 versus 90 ± 10 mm Hg, p < 0.05). There were no differences in blood pressure responses after nifedipine treatment or no drug. Heart rate responses were not altered by diltiazem or verapamil; after nifedipine administration, post-shock heart rates were slower. After treatment with diltiazem and verapamil there was a modest reduction in percent shock success across all energy levels (diltiazem: 28% ± 7% versus 17% ± 6%, 71% ± 9% versus 52% ± 14%, and 87% ± 13% versus 82% ± 11% at 25 J, 50 J, and 100 J, respectively [ p < 0.05 ]; verapamil: 50% ± 14% versus 15% ± 2%, 64% ± 11% versus 44% ± 14%, and 82% ± 9% versus 72% ± 13%, respectively [ p < 0.05 ]). Nifedipine did not alter shock success rates. This study suggests that calcium channel blocking drugs blunt the adrenergic response to defibrillation.

Interoceptive processes in cardiac phobia and panic disorder

The hemodynamic response to sequences of ventricular fibrillation and defibrillation includes an adrenergic component that is important for the maintenance of blood pressure after successful defibrillation. Because calcium channel blocking drugs have antiadrenergic effects, we hypothesized that they might blunt the adrenergic response to defibrillation. Ventricular fibrillation was induced in 35 closed-chest dogs. Each recaived 4 to 7 direct current transthoracic shocks at three energy levels to determine defibrillation energy requirements. Heart rate and blood pressure were recorded. Energy sequences were repeated after 45 minutes of no intervention (control, n = 5) or after 45-minute infusions of diltiazem (0.1 mg/kg/min, n = 10), verapamil (0.1 mg/kg bolus plus 0.01 mg/kg/min, n = 10), or nifedipine (40 μg/min for 3 minutes plus 2 to 20 μg/min adjusted to maintain a 10 mm Hg drop in mean arterial pressure, n = 10). Our results show that the normal post-shock rise in mean arterial pressure was blunted by the calcium channel blockers diltiazem (systolic arterial pressure at 15 and 60 seconds post-shock, pre-drug versus post-drug: 102 ± 9 versus 64 ± 9 mm Hg and 113 ± 10 versus 87 ± 6 mm Hg; p < 0.05) and verapamil (108 ± 9 versus 78 ± 12 mm Hg and 113 ± 7 versus 90 ± 10 mm Hg, p < 0.05). There were no differences in blood pressure responses after nifedipine treatment or no drug. Heart rate responses were not altered by diltiazem or verapamil; after nifedipine administration, post-shock heart rates were slower. After treatment with diltiazem and verapamil there was a modest reduction in percent shock success across all energy levels (diltiazem: 28% ± 7% versus 17% ± 6%, 71% ± 9% versus 52% ± 14%, and 87% ± 13% versus 82% ± 11% at 25 J, 50 J, and 100 J, respectively [ p < 0.05 ]; verapamil: 50% ± 14% versus 15% ± 2%, 64% ± 11% versus 44% ± 14%, and 82% ± 9% versus 72% ± 13%, respectively [ p < 0.05 ]). Nifedipine did not alter shock success rates. This study suggests that calcium channel blocking drugs blunt the adrenergic response to defibrillation.

Effect of xamoterol in a patient with idiopathic autonomic failure

We report the effect of xamoterol on autonomic, humoral and haemodynamic function in a patient with idiopathic autonomic neuropathy. Xamoterol produced marked symptomatic improvement, slightly increased heart rates in the sitting, supine and upright tilt positions and higher blood pressures while seated and on recovery from upright tilt. There were, however, no differences in blood pressure responses following a meal or during head-up tilt. We suggest that before ascribing symptomatic benefit to xamoterol in this condition, objective haemodynamic improvement should be recorded. Further studies of treatment in idiopathic autonomic failure require to be placebo controlled.

Does anxiety or cardiovascular reactivity have a causal role in hypertension?

Anxiety, stress, and cardiovascular reactivity (CVR) are variously believed to play a role in sustained hypertension. Although acute anxiety or stress elicits acute pressor responses, there is little support for their significant role in sustained hypertension. Anxiety correlates poorly with CVR, and blood pressure levels and anxiolytics do not sustain blood pressure lowering in subjects with hypertension-associated anxiety. Chronic anxiety disorders tend to be characterized by relatively low blood pressure and prevalence of sustained hypertension. Blood Pressure Regulation in hypertension is normal, and normo- and hypertensives have similar ambulatory blood pressure variability. Laboratory CVR fails to predict variability in natural environments, hyperreactors do not exhibit increased variability in natural environments, and the increased variability and ambulatory reactivity that is "accounted for" by laboratory responses is small. These findings do not support the belief that hypertension is related to a summation of heightened pressor responses over time. Antihypertensives normalize elevated blood pressures but do not alter CVR in the laboratory or variability in natural environments, probably because of a dual central regulation of resting and reactive blood pressures. Psychological stress responses result from selective neuronal activation rather than from generalized sympathetic neural responses or dysregulation. Differences in blood pressure responses during various emotions are only quantitative, with no specificity of sympathoadrenal or emotional responses to stressors. It may be time to regard reactive cardiovascular responses as physiological, rather than as psychological, and to require much stronger evidence to confirm causal roles of anxiety, stress, and reactivity in sustained hypertension.

Exaggerated Sympathetic Nervous System Response to Extended Psychological Stress in Offspring of Hypertensives

The cardiovascular responses of 24 healthy young adult males with a parental history of hypertension and 24 males without a parental history of hypertension to an extended active-coping psychological stressor were compared under three drug conditions: placebo, the beta 1-blocking agent metoprolol, and the alpha 1-blocking agent prazosin. In the placebo condition, offspring of hypertensives exhibited significantly greater heart rate, blood volume pulse, and forearm blood flow responses to the task. They also exhibited a significantly greater initial decrease in forearm vascular resistance, which, in contrast to the offspring of normotensives, was no longer significantly different from baseline levels by the end of the session. No group differences in blood pressure response were observed. Metoprolol eliminated the differences in heart rate and forearm vascular resistance responses. Prazosin eliminated the difference in blood volume pulse response and elicited a sustained group difference in forearm vascular resistance. These results implicate the sympathetic nervous system in the exaggerated cardiovascular responsivity to psychological stress in individuals with a family history of essential hypertension. They also suggest that the pattern of increasing vascular resistance in response to this stressor observed in this and other studies in this laboratory reflects alpha-adrenergic activity and not neurohumorally independent autoregulation.

Effect of calcium channel blockers on hemodynamic responses to defibrillation

The hemodynamic response to sequences of ventricular fibrillation and defibrillation includes an adrenergic component that is important for the maintenance of blood pressure after successful defibrillation. Because calcium channel blocking drugs have antiadrenergic effects, we hypothesized that they might blunt the adrenergic response to defibrillation. Ventricular fibrillation was induced in 35 closed-chest dogs. Each recaived 4 to 7 direct current transthoracic shocks at three energy levels to determine defibrillation energy requirements. Heart rate and blood pressure were recorded. Energy sequences were repeated after 45 minutes of no intervention (control, n = 5) or after 45-minute infusions of diltiazem (0.1 mg/kg/min, n = 10), verapamil (0.1 mg/kg bolus plus 0.01 mg/kg/min, n = 10), or nifedipine (40 μg/min for 3 minutes plus 2 to 20 μg/min adjusted to maintain a 10 mm Hg drop in mean arterial pressure, n = 10). Our results show that the normal post-shock rise in mean arterial pressure was blunted by the calcium channel blockers diltiazem (systolic arterial pressure at 15 and 60 seconds post-shock, pre-drug versus post-drug: 102 ± 9 versus 64 ± 9 mm Hg and 113 ± 10 versus 87 ± 6 mm Hg; p < 0.05) and verapamil (108 ± 9 versus 78 ± 12 mm Hg and 113 ± 7 versus 90 ± 10 mm Hg, p < 0.05). There were no differences in blood pressure responses after nifedipine treatment or no drug. Heart rate responses were not altered by diltiazem or verapamil; after nifedipine administration, post-shock heart rates were slower. After treatment with diltiazem and verapamil there was a modest reduction in percent shock success across all energy levels (diltiazem: 28% ± 7% versus 17% ± 6%, 71% ± 9% versus 52% ± 14%, and 87% ± 13% versus 82% ± 11% at 25 J, 50 J, and 100 J, respectively [ p < 0.05 ]; verapamil: 50% ± 14% versus 15% ± 2%, 64% ± 11% versus 44% ± 14%, and 82% ± 9% versus 72% ± 13%, respectively [ p < 0.05 ]). Nifedipine did not alter shock success rates. This study suggests that calcium channel blocking drugs blunt the adrenergic response to defibrillation.

Forearm blood flow responses of offspring of hypertensives to an extended stress task.

The forearm blood flow and other cardiovascular responses of 10 healthy young men with a parental history of hypertension to an extended laboratory stressor were compared with the responses of 10 age-matched men with normotensive parents. To eliminate the effects of the anticipation of stress on baseline measures, all subjects participated in a separate 1-hour counterbalanced baseline session in which no stress was presented. There were no significant differences between the two groups in resting blood pressure, heart rate, blood volume pulse, forearm blood flow and vascular resistance, and self-report anxiety, although offspring of hypertensive parents exhibited marginally greater (p = 0.08) forearm blood flow at rest. During the stress session, subjects played video games for 1 hour and avoided mild electric shocks depending on performance. Offspring of hypertensive parents exhibited significantly greater heart rate (+19 +/- 6 vs. +3 +/- 2%), forearm blood flow (+52 +/- 14 vs. +9 +/- 4%), and self-report anxiety (+25 +/- 6 vs. +9 +/- 3%) responses to the task. There were no significant group differences in blood pressure response to the task. Significant positive correlations between forearm blood flow and heart rate responses to the task were observed. These findings extend earlier results that suggested healthy young offspring of hypertensive and normotensive parents may exhibit different patterns of hemodynamic response to stress in the absence of differences in resting blood pressure or blood pressure responsiveness to stress.

Kinetic-dynamic relationships and antihypertensive mechanisms of ketanserin in essential hypertension.

This study of ketanserin illustrates the use of concentration-effect analysis in clinical investigations of antihypertensive mechanisms and the factors responsible for interindividual differences in blood pressure response. Using an integrated kinetic-dynamic model the acute and chronic responses to ketanserin were characterized for each individual patient in terms of blood pressure fall per unit drug concentration. Two principal findings were obtained from this approach. (1) There was a significant reduction in responsiveness to ketanserin during chronic treatment: on average, -0.47 after the first dose compared with -0.25 mmHg/ng per ml after 1 month. (2) There was a significant change in the parameter keq, which characterizes the temporal discrepancy between the time profiles for plasma drug concentration and effect: from a mean value of 0.49 (first dose) to 1.86/h (1 month). There was no significant relationship between the responsiveness to ketanserin and patient age, peripheral alpha 1-adrenoceptor blockade or initial blood pressure. These results suggest that there is a change in the relative contributions of the component antihypertensive mechanisms during continued treatment with ketanserin. Furthermore, there is no clear relationship between patient age and responsiveness to ketanserin.

Age and antihypertensive drugs (hydrochlorothiazide, bendroflumethiazide, nadolol and captopril)

Three double-blind Veterans Administration Cooperative Studies are reviewed to determine age-related changes in response to antihypertensive agents. In the first study 312 patients received hydrochlorothiazide titrated from 25 to 100 mg twice daily to lower diastolic blood pressure (BP) to <90 mm Hg. Of 121 patients aged 55 to 65 the decrease in BP averaged −21.8 −12.9 mm Hg, while in the 191 patients younger than 55 the reduction averaged −15.7 −11.5 mm Hg (p < 0.001; p = 0.048, respectively). Both systolic and diastolic BP reductions averaged significantly more in older whites; in older blacks it was systolic BP only. An additional 298 patients received titrated doses of propranolol alone, in this group there were no significant differences in BP response between younger patients and patients aged 55 to 65 except in the subgroup of white patients older than 60, in whom the systolic reduction was significantly less than in the younger patients. In a second study of bendroflumethiazide alone and with nadotol, systolic BP decreased more in older than in younger patients but there was no agerelated reduction with nadotol atone. In the third trial captopril was first given atone and later with hydrochlorothiazide. There were no age-related differences with captopril alone, but after the addition of hydrochlorothiazide there was a trend toward a greater antihypertensive response in the patients aged 55 to 69. Thus, responsiveness of older patients varies with the type of antihypertensive drug. Age appears to increase the antihypertensive response to thlazide diuretics but not to β-adrenergic blocking drugs or to captopril.

Blood Pressure and Calcium Supplementation-Reply

In Reply.— The comments and questions of Drs Cappuccio and Strazzullo are appreciated. We, too, believe that rigorously designed and carefully presented studies are needed to answer basic questions about the relationship between oral calcium intake and blood pressure. Our choice of a normotensive population was justified by our interest in nonpharmacologic approaches to the primary prevention of hypertension as well as the treatment of established hypertension. The entire range of the blood pressure distribution should be examined with respect to proposed interventions to determine their potential for prevention and treatment of hypertension. Only two previously reported studies 1,2 have examined the impact of increased calcium intake in normotensives and none have specifically addressed the possibility of racial differences in blood pressure response to calcium supplementation. It is a matter of opinion whether covariance is appropriate when a randomized design is employed and baseline values are not significantly different between

The antihypertensive efficacy of nifedipine alone and in combination in general practice.

A multi-centre study in general practice involving 3242 hypertensive patients, aged up to 70 years, was carried out to evaluate the efficacy and tolerability of nifedipine used alone or in combination with other antihypertensive agents in step-care treatment. Patients were treated for up to 8 weeks with one of four regimens: nifedipine monotherapy; diuretic and nifedipine; beta-blocker plus nifedipine; and nifedipine added to a combination of diuretic and beta-blocker. All patients received 20 mg nifedipine, in slow-release tablet form, twice daily; at Week 4, dosage was increased to 40 mg twice daily in 8.5% patients because their supine diastolic blood pressure still exceeded 95 mmHg. Changes in mean blood pressure of the total study group for systolic and diastolic, supine and standing, were highly significant both from baseline (Week 0) to Week 4 (p less than 0.0001) and from baseline to Week 8 (p less than 0.0001). Mean blood pressure reduction was 29/18 mmHg supine and 27/18 mmHg standing. Statistical differences in blood pressure response between age, sex and treatment groups were not of clinical significance. Statistically significant reductions in heart rate (mean 1.9 beats/min, p less than 0.001) and body weight (mean 0.48 kg, p less than 0.001) were noted, but were not of clinical relevance. Nifedipine produced a net increase of 12% in side-effects at Week 4 compared to the profile at entry.

Disodium cromoglycate, a mast‐cell stabilizer, alters postradiation regional cerebral blood flow in primates

Early transient incapacitation (ETI) is the complete cessation of performance during the first 30 min after radiation exposure, and performance decrement (PD) is a reduction in performance at the same time. Supralethal doses of radiation have been shown to produce a marked decrease in regional cerebral blood flow in primates concurrent with systemic hypotension and a dramatic release of mast-cell histamine. In an attempt to elucidate mechanisms underlying the radiation-induced ETI/PD phenomena and the postradiation decrease in cerebral blood flow, primates were given the mast-cell stabilizers disodium cromoglycate (DSCG) or BRL 22321 (Beecham Pharmaceuticals, Research Division) before exposure to 100 Gy whole-body gamma radiation. Hypothalamic and cortical blood flows were measured by hydrogen clearance, before and after radiation exposure. Systemic blood pressures were determined simultaneously. The data indicated that DSCG was successful in diminishing postradiation decrease in cerebral blood flow. Irradiated animals pretreated with DSCG, showed only a 10% decrease in hypothalamic blood flow 60 min postradiation, while untreated, irradiated animals showed a 57% decrease. The cortical blood flow of DSCG treated, irradiated animals showed a triphasic response, with a decrease of 38% at 10 min postradiation, then a rise to 1% below baseline at 20 min, followed by a fall to 42% below baseline by 50 min postradiation. In contrast, the untreated, irradiated animals showed a steady decrease in cortical blood flow to 79% below baseline by 50 min postradiation. There was no significant difference in blood-pressure response between the treated and untreated, irradiated animals. Systemic blood pressure showed a 60% decrease at 10 min postradiation, falling to a 71% decrease by 60 min. The effects of BRL 22321 in altering postradiation blood flow in the cerebral cortex and hypothalamus were intermediate between the irradiated controls and those pretreated with DSCG, but were not considered to be significant at the concentration employed. The overall results of this study indicate that the postradiation decrease in regional cerebral blood flow may be partially alleviated by treatment with a mast-cell stabilizer.

Neurohumoral factors in borderline hypertension.

Role of neurohumoral factors in borderline hypertension was evaluated in comparison to those in established hypertension. Although there was no significant difference in urinary noradrenaline between the 2 groups, urinary adrenaline was significantly higher in borderline hypertension than in established hypertension. During head-up tilt and Schellong's test a significant increase of diastolic blood pressure was demonstrated in borderline hypertension, whereas a significant decrease of systolic blood pressure was observed without any significant change of diastolic pressure in established hypertension. There was no significant difference in blood pressure response to cold pressor test, plasma volume, total body potassium and plasma renin activity (PRA) between the 2 groups. Blood pressure did not change after administration of captopril in normal subjects but it decreased significantly after captopril in patients with borderline hypertension even when blood pressure became normotensive during hospitalization. Blood pressure decreased significantly after captopril in patients with established hypertension. However, no significant relationship between the pretreatment PRA and the reduction of mean blood pressure was observed in both groups. It can be concluded from the present study that borderline hypertension is intermediate between normal subjects and established hypertension and that both the renin-angiotensin system and the kinin-prostaglandin system play some role in the maintenance of blood pressure in borderline hypertension.

Abnormal relationship between sodium intake and sympathetic nervous system activity in salt-sensitive patients with essential hypertension

To examine the mechanisms underlying the sensitivity to sodium intake in a subset of patients with essential hypertension, we studied the effects of different sodium intake (10, 100, 200 mEq/day) on blood pressure, the function of the renin-angiotensin-aldosterone system, and on blood levels of catecholamines in 20 patients with essential hypertension and 10 normal subjects. Mean blood pressure (MBP) was not different in hypertensive and normal subjects during low sodium diet. But, with high sodium intake, MBP increased by at least 10% in 12 patients (salt-sensitive), whereas in the remaining 8 patients (salt-resistant) and in normal subjects, MBP did not change significantly. This phenomenon cannot be attributed to differences in sodium retention because the percent change in body weight ad the urinary sodium excretion in the salt-sensitive patients was not different than it was in salt-resistant patients or in normal subjects. The observed difference in blood pressure response to high sodium intake in salt-sensitive patients is also not dependent on an impaired suppressibility of the renin-angiotensin-aldosterone system because there were no significant differences in the basal levels of PRA and aldosterone between the groups, and because the orthostatic increments in PRA were significantly lower in salt sensitive than they were in the salt-resistant patients and in normal subjects. Plasma norepinephrine (NE) levels were not significantly different between normal subjects or hypertensive patients while on low sodium intake. But during high sodium intake, they decreased significantly (P less than 0.05) in normal subjects (from 22 +/- 3.4 to 12 +/- 2.3 ng/dl) and in salt-resistant patients (from 17 +/- 4.5 to 13 +/- 2.4 ng/dl) but not in salt-sensitive patients (from 20 +/- 1.9 to 22 +/- 3.2 ng/dl). Furthermore, the majority of salt-sensitive patients displayed inappropriately high plasma NE in relation to their urine excretion of sodium during high sodium intake. Finally, the increments in plasma NE after 5 min of standing were significantly greater in salt-sensitive patients than they were in salt-resistant patients and normal subjects during both low or high sodium intake. These data indicate that a subset of patients with essential hypertension may have impaired suppressibility of plasma NE during high sodium intake, which suggests hyperactivity of the sympathetic nervous system in these patients. These aberrations may be responsible for the increase in MBP in the salt-sensitive patients during high sodium intake.

Age-related difference in cerebral perfusion pressure response to acute hypoxia in neonatal puppies.

Acute hypoxia is known to increase cerebral blood flow and intracranial pressure in the fetus and newborn. The combined effects of these changes on cerebral perfusion pressure are unknown. We investigated cerebral perfusion pressure changes in newborn puppies of two age groups (group I, mean age 28 days, group II, mean age 11 days) during acute, severe hypoxia. The results indicate that (1) in both groups the intracranial pressure increases within seconds following the onset of hypoxia; (2) the mean arterial blood pressure drops almost precipitantly in older animals, whereas in group II, the blood pressure is maintained near baseline values up to 4 min, and (3) because of differences in blood pressure responses the cerebral perfusion pressure falls dramatically in group I, whereas in younger animals normotensive response to hypoxia helps maintain the cerebral perfusion pressure for a longer period. We conclude that in young animals early normotensive response to hypoxia assures adequate transmural pressure for the perfusion of brain which may be a built-in protective factor.

Attenuated depressor response to arachidonic acid and prostaglandins in unclipped renal hypertensive rats.

1 In renal hypertensive rats (one-clip, two-kidney type) blood pressure returned to a normotensive level within 24 h after the removal of the renal artery clip (unclipping). 2 The decrease in blood pressure caused by intravenous administration of arachidonic acid, prostaglandin E2 and prostaglandin I2 was significantly reduced in these unclipped rats. 3 The hypotensive response to bradykinin and acetylcholine was the same in unclipped rats and in control rats. 4 Nephrectomy abolished the difference in blood pressure response to arachidonic acid and the two prostaglandins between unclipped and control rats. 5 An enhanced secretion of renin, as indicated by the absence of an increase in plasma renin activity, did not seem to be involved in the attenuated blood pressure response to arachidonic acid in unclipped rats.