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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.

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.

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.

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.

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.

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.