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The effect of felodipine 10 mg oral solution or placebo on peripheral haemodynamics and the response of the forearm resistance vessels to venous occlusion was studied in seven normotensive individuals. Felodipine produced a significant fall in diastolic blood pressure (DBP max = -15 mm Hg), a rise in heart rate (heart rate max = +15 beats min- 1) (both P less than 0.01), and an overall fall in calculated forearm vascular resistance (calculated forearm vascular resistance max = -19.6 units, P less than 0.001). Felodipine had no significant effect on the vasodilator response, but limited the vasoconstrictor response following venous occlusion. These observations suggest that felodipine is a potent vasodilator and interferes with the myogenic response of vascular smooth muscle of the forearm resistance vessels. [ABSTRACT FROM AUTHOR]

Seven untreated patients with essential hypertension but without target organ damage were admitted to hospital. Urine was collected the following day from 08.00 to 13.00 h, 13.00 to 18.00 h, and 18.00 to 08.00 h. The protocol was repeated the next day following 30 mg oral nicardipine. Intra-arterial blood pressure (IABP), plasma volume, and plasma renin activity (PRA) also were measured daily. Following the single-dose study, the patients were treated as outpatients and received oral nicardipine 20, 30, or 40 mg four times daily. They were readmitted 2 months later for further study, at which time the protocol was repeated. Urine output between 08.00 and 13.00 h significantly increased after the single- and multiple-dose studies. Following the single-dose study, this diuresis was associated with a natriuresis. Urine output increased over the 24 h following multiple-dose treatment, but this increase was not statistically significant. During the multiple-dose 24 h study, there was an increase in urinary potassium (P less than 0.05). Mean IABP was reduced significantly after the single- and multiple-dose studies (P less than 0.02 and less than 0.05, respectively). During the study, there were no significant changes in plasma volume, weight, or plasma renin activity. [ABSTRACT FROM AUTHOR]

1 Ten untreated hypertensive patients underwent 24 h continuous intra- arterial ambulatory monitoring of blood pressure (BP) and M-mode echocardiography. 2 They were treated with once-daily timolol and followed up at 2, 4, 8 and 12 weeks when dosage was titrated against BP control (indirect measurement) and degree of beta-adrenoceptor antagonism (submaximal bicycle ergometry and sub-lingual GTN). 3 Sixteen weeks after commencing therapy, nine patients underwent repeat continuous ambulatory monitoring of BP and M-mode echocardiography. 4 Casual BP was significantly reduced during the follow-up period at 2, 4, 8 and 12 weeks. 5 A reduction of BP was seen throughout the 24 h although this did not achieve statistical significance when sympathetic activity was low. 6 Echocardiographic measurement of left ventricular mass was significantly reduced after 16 weeks treatment. [ABSTRACT FROM AUTHOR]

1 Thirteen hypertensive patients completed a double-blind comparison of placebo, acebutolol 200 mg twice daily and acebutolol 400 mg once daily, administered for 4 weeks in random order. 2 Blood pressure and heart rate were significantly reduced by both acebutolol treatments. The mean reduction of resting pressure 12 h after 200 mg twice daily (12/7 mmHg) was similar to that 24 hr after 400 mg once daily (13/9 mmHg). 3 Compared to placebo, reductions in exercise heart rate and systolic pressure at 12 h after 200 mg twice daily and 24 h after 400 mg once daily were significant and similar. 4 Beta-adrenoceptor antagonism was also assessed by inhibition of the heart rate response to sublingual glyceryl trinitrate taken in the standing position. Both acebutolol treatments reduced the response; the reduction after twice daily treatment (mean 25 beats/min) was significantly greater than after once daily treatment (mean 19 beats/min). 5 There was no difference in blood pressure control between acebutolol administered once and twice daily in a total daily dose of 400 mg. [ABSTRACT FROM AUTHOR]

Objective: Baroreflex sensitivity (BRS) increases during sleep, whereas arterial blood pressure falls. Some hypertensive patients do not have a nocturnal fall in blood pressure (non-dippers). The objective was to ascertain whether there is a difference between 24 h BRS values in dippers and non-dippers that might account for the difference in nocturnal blood pressure behaviour., Design: In a group of consecutive untreated hypertensive patients undergoing 24 h ambulatory intra-arterial blood pressure (IABP) monitoring, 18 were non-dippers i.e., their mean IABP during sleep failed to drop by 10% of their waking IABP. Each non-dipper was matched for age and waking IABP with two dippers. The BRS had previously been assessed with the "Oxford' bolus phenylephrine technique; spontaneous BRS was assessed throughout the 24 h period by off-line computer analysis of spontaneous variations in IABP and R-R interval., Results: In both groups there was a significant increase in spontaneous BRS during sleep (P < 0.0001 for dippers, P < 0.0001 for non-dippers). There was no significant difference between spontaneous BRS in dippers and non-dippers, when they were either awake or asleep., Conclusion: BRS did not differ significantly between dippers and non-dippers, when they were either awake or asleep. Changes in BRS during sleep are not likely to account for the abnormal dipping pattern in a minority of hypertensives and are not likely to contribute to the normally observed nocturnal fall in blood pressure.

Objectives: To define the effects of long-term thyroxine treatment upon heart rate, blood pressure, left ventricular systolic function, and left ventricular size, as well as indices of autonomic function, and to compare findings with those in patients with thyrotoxicosis before and during treatment., Design: Cross sectional study of patients prescribed thyroxine long term (n = 11), patients with thyrotoxicosis studied at presentation (n = 23), compared with controls (n = 25); longitudinal study of patients with thyrotoxicosis studied at presentation and serially after beginning antithyroid drug treatment (n = 23)., Methods: 24 h ambulatory monitoring of pulse and blood pressure, echocardiography, forearm plethysmography, and autonomic function tests., Results: Long-term thyroxine treatment in doses that reduced serum thyrotrophin to below normal had no effect on blood pressure, heart rate, left ventricular systolic function or stroke volume index, but was associated with an 18.4% increase in left ventricular mass index (mean (SEM) 101.9 (3.09) g/m2 v controls 86.1 (4.61), P < 0.01). Thryoxine treatment, like thyrotoxicosis, had no effect on tests of autonomic function. Untreated thyrotoxicosis resulted in pronounced changes in systolic and diastolic blood pressure and an increase in heart rate during waking and sleep. Patients with thyrotoxicosis at presentation had an increase in left ventricular systolic function (ejection fraction 70.5 (1.66)% v 65.4 (1.79), P < 0.01; fractional shortening 40.4 (1.54)% v 35.6 (1.46), P < 0.01), increased stroke volume index (45.9 (2.4) ml/m2 v 36.6 (1.7), P < 0.001), and an increase in forearm blood flow, and decrease in vascular resistance. They had a similar degree of left ventricular hypertrophy to that associated with thyroxine treatment (99.3 (4.03) g/m2); all changes were corrected within 2 months by antithyroid drugs., Conclusions: The development of left ventricular hypertrophy in patients receiving thyroxine in the absence of significant changes in heart rate, blood pressure, and left ventricular systolic function is consistent with a direct trophic effect of thyroid hormone on the myocardium. The presence of left ventricular hypertrophy determines that further studies are essential to assess cardiovascular risk in patients taking thyroxine long term.

A validation study of the Takeda TM-2420 ambulatory blood pressure recorder was performed on 10 subjects using the Oxford ambulatory intra-arterial recording apparatus during unrestricted activity. Electronic linkage of the two recorders ensured simultaneous blood pressure readings, taken from opposite arms. Although there was close approximation of intra-arterial and automated sphygmomanometric recordings over the range of blood pressure encountered in this study, there was a wide scatter of points and a tendency for the machine to underestimate systolic pressure by more than 15 mm Hg in the hypertensive range (systolic blood pressure more than 160 mm Hg) was detected. These findings suggest that automated recording of blood pressure during unrestricted activity may have a proportion of artifactual readings. Although simultaneous intra-arterial blood pressure recording may not be appropriate for widespread use in device validation, this study illustrated some potential disadvantages of the current validation recommendations, namely, the absence of assessment of device accuracy during unrestricted and ambulatory activity.

The effects of monotherapy with the angiotensin converting enzyme inhibitor benazepril (10 mg once daily) on cardiovascular baroreceptor reflexes were determined in 10 patients with essential hypertension using a randomized, double-blind, placebo-controlled, cross-over protocol. Early sino-aortic baroreceptor/heart rate reflex resetting was apparent with acute treatment; this effect persisted throughout the active treatment period. Changes in baroreflex sensitivity did not appear to mediate the hypotensive effect of benazepril.

The effect of xamoterol on the orthostatic hypotension associated with Shy-Drager syndrome was investigated in three patients. Intra-arterial blood pressure was measured during a control period and during treatment with xamoterol, both in a cardiovascular investigation laboratory and for 24 h of unrestricted activity using portable apparatus. Xamoterol lessened the total number of symptomatic episodes of orthostatic hypotension by 67 per cent. Average untreated 24-h intra-arterial blood pressure was 132/78 mmHg; during treatment with xamoterol it rose to 138/90 mmHg. However episodes of severe hypertension (defined as a systolic intra-arterial blood pressure above 200 mmHg) were more frequent with xamoterol. Although xamoterol attenuated orthostatic hypotension, careful monitoring of ambulatory blood pressure may be necessary, particularly at the start of treatment, because of the development of severe supine hypertension. Intravenous test doses of xamoterol did not predict either the attenuation of orthostatic hypotension or the development of supine hypertension in all patients.

1. Ambulatory blood pressure recordings were made over a 48 h period on six hypertensive patients. The conditions of study were standardized, particularly with regard to physical activity, and during one period of each day the patients were randomly allocated to be active or inactive. 2. Results show that blood pressure was highest during physical activity and lowest during sleep. There was no significant difference between the arterial pressures measured during the same physical activities carried out at the same time each day. However, during the same time on consecutive days when activity was randomized, there was a significant difference between the pressure recordings during physical activity compared with those during inactivity. Heart rate changes showed a similar trend during the randomized period. 3. Physical activity and sleep have a profound effect on continuous arterial blood pressure recordings and these are independent of time alone. These observations should be taken into account when using this ambulatory system to assess hypotensive therapy.

50 patients with mild to moderate essential hypertension underwent M-mode echocardiography and continuous intra-arterial ambulatory monitoring of blood pressure. Indices of left-ventricular (LV) mass were derived from echocardiographic data by standard formulae. 43 of the patients were followed up for 12+/-7 months with repeat M-mode echocardiography, and casual blood-pressure measurements. 25 of these patients received antihypertensive therapy and 18 were untreated. Mean 24 h systolic blood pressure was significantly correlated with echocardiographic LV mass; mean 24 h diastolic blood pressure was also correlated, but the relation was weaker. In the treated group there was a significantly greater fall in blood pressure and LV mass index than in the untreated group, and there was a significant correlation between the fall in systolic blood pressure and the fall in LV mass index in the treated group. Systolic blood pressure appears to be an important factor in the pathogenesis of LV hypertrophy, and in hypertensive patients changes in LV mass assessed by echocardiography correlate with changes in blood pressure.

Nine elderly and 11 young hypertensives underwent continuous ambulatory monitoring of blood pressure (BP), assessment of cardiovascular reflexes and M-mode echocardiography as hospital in-patients prior to treatment with once-daily indapamide (2.5 mg). They were followed as out-patients for 4 months during which time casual BP was measured at monthly intervals. The patients were then readmitted to hospital and studied using the same protocol under similar standardised conditions. The results showed that indapamide reduced casual and ambulatory BP in both young and elderly although the most marked effect was seen on systolic BP. Assessment of cardiovascular reflexes indicates that at least part of the hypotensive action of indapamide is due to a diuretic effect. Treatment with indapamide has comparable results on both young and elderly.

Sixteen untreated black patients with mild-to-moderate hypertension and no evidence of target organ damage were matched for age, sex, casual blood pressure (BP), and socioeconomic status with 16 white hypertensives. All patients were studied under standardized conditions in the hospital where they underwent continuous intraarterial ambulatory monitoring of BP and assessment of BP control mechanisms. BP characteristics over prolonged periods of recording were similar for both groups, as were sinoaortic baroreflex activity and pressor response to isometric and dynamic exercise and to cold. Fasting cholesterol and triglyceride levels in both groups were similar. Resting plasma renin activity (PRA) was significantly lower in blacks, but no difference was observed in resting plasma norepinephrine levels. Urinary excretion of NA+ and K+ was also similar in both groups. Thus, results showed that casual BPs matched for black and whites, and recorded over a prolonged period, were similar in pattern, variability, and response to pressor stimuli. It appears that, if BP contributes to the different patterns of morbidity in blacks and whites, it is more likely to be the actual level of BP rather than differences in BP characteristics.

Thirty-two patients with mildly elevated blood pressure (BP), but without target organ damage, attended a BP measuring clinic where duplicate BP measurements were made on 12 visits. During visits 1-3, BP showed a systematic decrease which varied from patient to patient. During visits 4-12, no further systematic changes in BP were observed. During the latter period, between-visit variation in BP was substantial, the standard deviation of the difference in BP from one visit to another being 10.4 mmHg for systolic, 6.8 mmHg for diastolic (phase IV) and 7.0 mmHg for diastolic (phase V). These values were used to determine the chance that the BP estimated after a number of visits differed from the average stable BP. After visit 4, the chance of a difference of 5 mmHg or more was 0.50 systolic blood pressure (SBP) and 0.32 diastolic blood pressure (DBP; phase V). Increasing the number of visits to six or more reduced the chance of error. Before initiating lifelong treatment in mild hypertensives free of target organ damage, BP should be recorded in duplicate on a minimum of six visits.

Plasma catecholamines were measured before and after treatment with beta-adrenoceptor antagonists in 17 hypertensive patients. Chronic treatment with beta-adrenoceptor antagonists caused substantial reductions in heart rate and intra-arterial blood pressure recorded continuously during ambulation. Before treatment, a quantitative relationship was observed between plasma norepinephrine and blood pressure and heart rate during a variety of activities; a similar relationship was also observed after chronic treatment five of six patients, suggesting that plasma norepinephrine remains an index of sympathetic activity despite the influence of beta-adrenoceptor antagonism. After treatment, plasma norepinephrine tended to be higher at any level of blood pressure, although not significantly so. Chronic treatment caused no significant change in mean resting plasma levels of norepinephrine and epinephrine. During exercise, plasma norepinephrine and epinephrine levels were significantly elevated above control after acute but not after chronic treatment. These observations do not support the hypothesis that beta-adrenoceptor antagonist drugs lower blood pressure in hypertensive man through a sympatholytic mechanism in he central nervous system or at peripheral presynaptic receptors.

Intra-arterial pressure was recorded continuously in 26 patients with uncomplicated essential hypertension under standardized conditions. Recordings were analyzed beat by beat to obtain mean pressures and variability, expressed as the standard deviation of the frequency histogram. The major factors influencing variability were the level of pressure and the intensity of physical activity; systolic variability increased with progressive impairment of sino-aortic baroreflexes. Diastolic pressure increased with the level of sympathetic activity as reflected by plasma norepinephrine levels. After allowance for the decrease of plasma renin activity (PRA) with age, direct relationships were observed between PRA (log values) and the level of pressure and systolic variability; plasma angiotensin II values did not correlate. Systolic variability increased with the systolic response to cold but was unrelated to the response to dynamic or isometric exercise. Variability also tended to increase with obesity and was unrelated to age, sex, or race.

We examined the effect of three antihypertensive agents with differing modes of action on blood pressure, heart rate, plasma catecholamines, plasma renin activity, and echocardiographic left ventricular mass. Twenty-six patients were studied; nine were treated with nifedipine, a calcium antagonist, nine were treated with timolol, a nonselective beta-blocker, and eight were treated with indapamide, a diuretic with some probable calcium antagonist properties. All drugs reduced blood pressure satisfactorily; the reduction of systolic blood pressure was not significantly different among the three drugs, but timolol reduced diastolic blood pressure by a greater amount than did either indapamide or nifedipine. Left ventricular (LV) mass was reduced equally by all three drugs. However, there were markedly different effects on the other parameters measured. Heart rate was reduced to a greater extent by timolol than by the other two drugs. Plasma renin activity was reduced by timolol, unchanged by nifedipine, and increased by indapamide. There were no significant changes in either adrenaline or noradrenaline with any of the three drugs. We conclude that these data do not support the hypothesis that the sympathetic nervous system is primarily responsible for left ventricular hypertrophy, and suggest that reduction of left ventricular mass with antihypertensive agents is not the property of any one class of drug.

1. Forearm venous plasma noradrenaline, heart rate and intra-arterial blood pressure were measured sequentially during and after upright bicycle exercise in five normotensive and six hypertensive patients. 2. Plasma noradrenaline increased significantly between 4 and 8 min during exercise. 3. On stopping exercise blood pressure and heart rate decreased rapidly whilst plasma noradrenaline increased in each subject to reach a maximum at a median time of 108 s after exercise. 4. Plasma noradrenaline decreased in five of six normotensive patients between the end of exercise and 2 min after exercise performed in the supine position. 5. Evidence in favour of a reflex increase in sympathetic activity after upright exercise is discussed.

The effect of environment on blood pressure was studied by recording intra-arterial pressure continuously in nine patients with essential hypertension during controlled periods of activity and rest at home and in hospital. Mean systolic pressure was higher at home (152 +/- 16 mm Hg) than in hospital (138 +/- 11 mm Hg, p less than 0.01), the difference being greatest during the period of activity (165 +/- 21 v 142 +/- 13 mm Hg, p less than 0.001); heart rates and diastolic pressures did not differ significantly at these times. Systolic pressure recorded by conventional sphygmomanometry was also higher at home (173 +/- 23 v 159 +/- 23 mm Hg, p less than 0.01), as was diastolic pressure (98 +/- 10 v 89 +/- 11 mm Hg, p less than 0.02). Systolic pressure was consistently higher at home, and this effect was independent of the pressure of an observer. This must be taken into consideration when assessing blood pressure and efficacy of treatment in hospital.

Thirteen elderly hypertensives (EH) underwent ambulatory blood pressure (BP) monitoring and measurement of cardiovascular reflexes. The results were compared with elderly normotensives (EN) and young hypertensives (YH) in studies using the same protocol. There was a greater disparity between casual systolic BP (SBP) and ambulatory awake SBP in EH than EN or YH. Variability of SBP was greater in the elderly than in the young, whilst baroreflex activity was reduced in the elderly, more markedly so in EH. Response to tilt and pressor tests were similar in EH and EN. EH showed greater changes in response to tilt and dynamic exercise than YH. The results suggest an exaggerated response to casual BP measurement in EH. The reduced baroreflex activity in EH could be associated with greater degenerative changes. The EH are exposed to greater peaks of BP than EN in response to pressor stimuli.

1. Sensitivity of the sino-aortic baroreflex was investigated before and after acute (23 patients) and chronic (23 patients) beta-adrenoreceptor antagonism in patients with essential hypertension. 2. Sensitivity was inversely related to age (r = -0.60) and systolic blood pressure (r = -0.46); a positive relationship was noted between sensitivity and initial pulse intervals (r = 0.40). 3. Sensitivity increased significantly in patients less than 40 years of age after chronic treatment. No change occurred after acute treatment or in older patients treated chronically. 4. The fall in ambulatory intra-arterial blood pressure after chronic treatment was unrelated to alteration of baroreflex sensitivity.

1. Continuous intra-arterial ambulatory monitoring of blood pressure was recorded in 46 patients with mild to moderate hypertension under standardized conditions. M-mode echocardiography was performed after recording and left ventricular mass index calculated by standard formulae. 2. Systolic blood pressure from continuous recording was significantly correlated with left ventricular mass index (mean 24 h: r = 0.543, n = 45, P less than 0.001). Diastolic blood pressure exhibited a weaker but still significant correlation with left ventricular mass index (mean 24 h: r = 0.318, n = 45, P less than 0.05). Casual systolic blood pressure was significantly correlated with left ventricular mass index (r = 0.476, n = 46, P less than 0.001) but casual diastolic blood pressure did not correlate with left ventricular mass index (r = 0.245, n = 46). Awake blood pressure variability, age, resting plasma renin activity and resting plasma noradrenaline levels did not have a significant correlation with left ventricular mass index. 3. Nine patients were treated for 16 weeks with once-daily timolol and repeat ambulatory monitoring and M-mode echocardiography was performed with the same protocol. 4. Once-daily timolol provided good 24 h control of blood pressure and repeat echocardiography showed a reduction in left ventricular mass index in that group of patients (t = 2.59, P less than 0.05).

A new method for analysing baroreflex sensitivity has been developed. It obviates the mathematical bias inherent in earlier methods and in addition provides a direct measurement of reflex latency. Sensitivity results obtained using this method in 25 patients with a wide range of ages and resting blood pressures were similar to, but consistently lower than, those achieved with the Oxford method. Baroreflex latency results ranged from 650 to 2900 ms (mean(SD) 1084(427) ms) and were reproducible within individuals. Sensitivity results were inversely related to age and resting systolic blood pressure. Reflex latency was not related to these variables or to resting heart rate or reflex sensitivity. This method was able to identify inadequate starting data and greatly reduced the analysis time.

Ambulatory blood pressure variability and forearm haemodynamics were measured in 23 untreated hypertensive patients with a mean casual blood pressure of 162/102(11/9) mmHg (without target organ damage). There was a good inverse correlation between blood pressure variability and the ability of the forearm resistance vessels to dilate after a period of venous occlusion. Previous work has shown that this vasodilatory component of the response to forearm venous occlusion is significantly reduced in hypertensive patients compared with normotensive controls and is probably an indicator of the compliance properties of these vessels. The present results suggest that blood pressure variability is greater when resistance vessels are stiffer and emphasise the need to account for this vascular factor in studies of blood pressure behaviour.

Thirteen elderly hypertensives underwent continuous ambulatory blood pressure (BP) monitoring and measurement of cardiovascular reflexes. The results were compared with elderly normotensives and young hypertensives studied using the same protocol. There was a greater disparity between casual systolic BP (SBP) and ambulatory awake SBP in the elderly hypertensives than either the elderly normotensives or young hypertensives. Variability of SBP was greater in the elderly than the young, whilst baroreflex activity was reduced in the elderly, and more markedly so in the elderly hypertensives. Response to tilt and pressor tests was similar for the elderly. The elderly hypertensives showed a greater fall of SBP in response to tilt and a greater rise of SBP during dynamic exercise than the young hypertensives. Stimulation of plasma renin activity (PRA) in response to upright tilt was less in the elderly hypertensives than the young hypertensives. Resting plasma noradrenaline (PNA) increased with age.

A new time related method of analysing the sinoaortic baroreceptor heart rate reflex, which determines reflex latency as well as sensitivity, was used to compare the results obtained with a phenylephrine ramp method (P) with those obtained using the whole of phase IV of Valsalva (V1) and using the phase IV systolic blood pressure overshoot alone (V2). Twenty five subjects with large ranges of age and resting blood pressures were studied. Each performed two standardised Valsalva manoeuvres and received three bolus injections of phenylephrine sufficient to cause transient pressor responses of 20-30 mmHg. Mean sensitivity values with P (6.2(3.5) ms.mmHg-1) were greater than those with V1 (4.6(2.3) ms.mmHg-1, p less than 0.001) and less than V2 (7.8(4.0) ms.mmHg-1, p less than 0.001). However, linear regression analysis showed a correlation of P with V1 (r = 0.76, p less than 0.0001) and with V2 (r = 0.80, p less than 0.0001). Reflex latency with P (1084(427) ms) was less than V1 (2416(423) ms, p less than 0.0001) and V2 (1504(441) ms, p less than 0.0005). Reflex sensitivity results obtained using phase IV of Valsalva's manoeuvre are proportionately related to phenylephrine results, but large errors were introduced into the absolute values obtained when relatively small changes were made to the method of analysis.

The effects of monotherapy with the angiotensin converting enzyme (ACE) inhibitor perindopril (8 mg once daily) on 24-h ambulatory intra-arterial blood pressure, forearm blood flow, left ventricular mass, vasoactive hormones and cardiovascular reflexes were determined in eight hypertensive patients using a randomized, double blind, placebo-controlled, cross-over protocol. Six weeks of perindopril treatment was associated with a significant reduction of ambulatory blood pressure and a significant increase in forearm blood flow. Whilst the haemodynamic responses to Valsalva's manoeuvre, tilt, isometric forearm exercise and cold pressor testing were unaffected by perindopril, significant augmentation of the bradycardia during facial immersion was seen after chronic therapy. Sino-aortic baroreceptor-heart rate reflex resetting was apparent within 2 h of the first dose; this effect persisted throughout the active treatment period. Withdrawal of treatment was associated with a persisting hypotensive effect and an increase in heart rate which was not accompanied by an increase in plasma catecholamines. We conclude that perindopril, in a dose of 8 mg once daily, was an effective antihypertensive agent. We postulate that chronic therapy was associated with a sustained increase in parasympathetic tone.

Nine patients with untreated essential hypertension (mean casual blood pressure 173/109 +/- 14/7 mm Hg) (+/- SD) were studied in the control state and after 16 weeks of treatment with nifedipine, 10 mg orally every 8 hours. Direct arterial blood pressure monitored continuously over 24 hours showed that nifedipine significantly reduced systolic and diastolic blood pressure throughout the day and the night. The variability of blood pressure was not altered by nifedipine therapy. There was no significant change in heart rate after nifedipine therapy. Chronic nifedipine therapy increased forearm blood flow and decreased forearm vascular resistance, consistent with its action as a vasodilator. The absolute blood pressure responses to tilt, handgrip and cold were reduced, but the percent increase in pressure was not altered by therapy. Plasma renin activity was not altered by chronic nifedipine therapy. At each study, the sensitivity and setting of the baroreflex response to i.v. phenylephrine was measured. After chronic nifedipine therapy there was resetting of the sinoaortic baroreflex and an increase in its sensitivity. Successful control of blood pressure with nifedipine led to a significant reduction in the left ventricular mass index.

Felodipine, a selective arteriolar dilator, was given to 13 hypertensive patients to assess its hypotensive effects and duration of action. Nine patients were treated with 5 mg three times a day and 4 with 10 mg three times a day. Mean blood pressures fell with both treatment regimens: 5 mg placebo 170/103 mmHg; 5 mg felodipine 148/91 mmHg; 10 mg placebo 154/93 mmHg; 10 mg felodipine 137/82 mmHg. Heart rates increased as blood pressures fell with both treatments. However, in the patients given 5 mg three times a day this effect was less noticeable after successive doses. Plasma concentrations of noradrenaline, both resting and tilted, increased after felodipine. There was a negative correlation between the fall in blood pressure and the increase in noradrenaline, suggesting that those patients with good baroreceptor reflexes were better able to counteract the effects of vasodilatation. Four of the nine patients treated with 5 mg felodipine three times a day experienced mild and transient adverse effects. Of the four patients treated with 10 mg three times a day, three experienced moderate to severe headache, and for this reason recruitment into this group was stopped. Felodipine at a divided daily dose of 15 mg effectively lowered blood pressure.

Nine patients with untreated, essential hypertension (mean casual blood pressure 173/109 +/- 14/7 mmHg (+/- s.d.] were studied in the control state and then following 16 weeks treatment with nifedipine 10 mg orally 8 hourly. Direct arterial blood pressure was monitored continuously over 24 hours and demonstrated that nifedipine significantly reduced systolic and diastolic blood pressure throughout the day and the night. The variability of blood pressure was not altered by nifedipine therapy. There was no significant change in heart rate after nifedipine therapy. At each study the sensitivity and setting of the baroreflex response to intravenous phenylephrine was measured. Following chronic nifedipine therapy there was re-setting of the sino-aortic baroreflex and an increase in its sensitivity.

Thirty-three elderly subjects--9 hypertensives, 15 with a history of unexplained falls and 9 asymptomatic volunteers, underwent 24 h continuous intra-arterial ambulatory blood pressure (BP) monitoring under controlled conditions. During this time their response to standardized exercise and baroreflex activity were assessed. The casual BP of the hypertensives was significantly higher than that of the other groups, but during ambulatory BP monitoring, the BP of all 3 groups fell and indeed diastolic BP (DBP) of the hypertensives and fallers was similar during the awake period of monitoring whilst all 3 groups had similar DBP during sleep. Variability of awake and sleep BP was similar. During exercise all 3 groups sustained similar increases in systolic BP (SBP) but the increase in DBP was lower in the volunteers. Baroreflex activity was similar in all groups. The results show little difference between the groups other than those pre-selected by casual BP measurement, and the parameters recorded reflect the process of ageing rather than specific abnormalities associated with the elderly hypertensives or fallers.

Intra-arterial pressure was recorded over 24 h in hypertensive patients before and during long-term treatment with beta-adrenoceptor antagonists given once daily under standardised conditions. Arterial pressure was reduced throughout the 24 h after the last dose as was variability of pressure during physical activity; variability during sleep and rest did not change significantly.

1. Intra-arterial pressure was recorded continuously in 26 patients with uncomplicated essential hypertension under standardized conditions. Pressure was analysed beat by beat by computer and variability measured as the standard deviation of the normally distributed frequency histogram. 2. Variability was strongly influenced by physical activity, being least during sleep and increasing progressively with bed rest and ambulation. Variability during daytime was not related to time. 3. Systolic variability correlated directly with systolic pressure. An independent inverse relationship with baroreflex sensitivity was observed. Systolic variability tended to increase with obesity. 4. None of the following were related independently with variability: age; race; sex; plasma renin activity; plasma angiotensin II; plasma noradrenaline; plasma adrenaline.