Supine Mean Arterial Pressure Research Articles

Differences in hormonal and renal vascular responses between normotensive patients with autosomal dominant polycystic kidney disease and unaffected family members

We tested the hypothesis that overactivity of the renal and systemic renin-angiotensin system is important to the pathogenesis of hypertension in autosomal dominant polycystic kidney disease (ADPKD). Up to 21 normotensive subjects with ADPKD and creatinine clearance > 70 ml/min/1.73 m2 were compared to 12 unaffected controls from the same families. Blood pressure, serum chemistry, sodium excretion, plasma renin and serum aldosterone and atrial natriuretic peptide (ANP) levels were measured at baseline, after acute sodium depletion, and after chronic higher sodium intake with and without enalapril. Effective renal plasma flow was measured by paraaminohippurate clearance in the higher sodium state, before and during an intravenous infusion of angiotensin II at 3 ng/kg/min. This was to test whether, by analogy to non-modulating essential hypertension, renal blood flow would fall to a lesser extent in the ADPKD subjects. The groups were comparable at baseline apart from a higher supine mean arterial pressure in the ADPKD group (median 91 vs. 81 mm Hg, P = 0.002). There were no significant differences between ADPKD and control subjects in blood pressure or hormonal response to sodium depletion. During chronically higher sodium intake, serum ANP was significantly higher (median 130 vs. 81 ng/liter, P = 0.0006) and plasma renin tended to be higher (median 20.5 vs. 13.5, P = 0.08) in ADPKD than in control subjects. The ADPKD group had a higher renal vascular resistance (median 7420 vs. 5915 dyn.sec.cm-5, P = 0.009) before angiotensin, but tended to have a lower percentage rise in resistance during angiotensin (median 31.5 vs. 46, P = 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)

Heart rate variability in time and frequency domains: effects of gallopamil, nifedipine, and metoprolol compared with placebo.

To assess the effects of three different antianginal drugs on heart rate, blood pressure, and heart rate variability. Randomised, single blind, placebo controlled, cross over study. University hospital. Nine healthy male volunteers. Oral administration of either 50 mg gallopamil, 20 mg nifedipine, 100 mg metoprolol, or placebo according to a random crossover plan. Time intervals between consecutive R waves in electrocardiograms measured with an accuracy of 5 ms from digital Holter recordings. Blood pressure monitored continuously by finger plethysmography. Metoprolol lowered heart rate from 62(6) to 51(5) beats/min (p = 0.003) after 78(23) minutes. Nifedipine provoked reflex tachycardia from 56(5) to 94(18) beats/min (p < 0.001) at 10(3) minutes after treatment followed by an exponential decline in heart rate to baseline values with a time constant of 34(7) min in seven subjects but 83 minutes in one volunteer. One subject showed no exponential decline in heart rate. Nifedipine significantly lowered the supine mean arterial pressure from 86(6) to 67(6) mm Hg (p = 0.004) after 11(2) minutes, indicating an acute reduction in arterial resistance. Gallopamil did not significantly change mean heart rate or blood pressure. In the sitting position three hours after administration gallopamil and metoprolol significantly lowered power spectral density in the low frequency band (0.03 Hz to 0.15 Hz) compared with placebo (p < 0.05). Nifedipine did not produce such an effect. Gallopamil and metoprolol both inhibit cardiac sympathetic activation compared with placebo, whereas nifedipine causes reflex sympathetic activation.

NaCl Induces Differential Changes of Regional Vascular Reactivity in Salt-Sensitive Versus Salt-Resistant Men

The objective of our study was to determine the structural or functional factors which increase forearm vascular resistance (FAVR) during a high NaCl diet in salt-sensitive (SS) volunteers. We studied the effects of 20 v 200 mEq/day NaCl diets on FAVR responses to norepinephrine (NE), angiotensin II (AII), nitroprusside, verapamil, and ischemia in 27 men. Twelve men had supine mean arterial pressure (MAP) on high NaCl which was greater than or equal to 5% above MAP on low NaCl and were consequently labeled SS. Eleven subjects had lower MAP on the high NaCl diet and were classified salt-resistant (SR). Basal FAVR was greater in SS (P less than .005) and unchanged in SR subjects on high (v low) NaCl. FAVR responses to NE and nitroprusside were not different between the two diets within either the SS or SR subgroups. FAVR responses to AII decreased during high NaCl in the SR (P less than .01), but not in the SS subset. The response to phentolamine and verapamil increased in SS (P less than or equal to .05) and tended to decrease in SR subjects (P less than .15) during high NaCl. In contrast, the vasodilator response to ischemia was impaired in the SS (P = .02) and enhanced in the SR (P = .02) group on high v low NaCl. Enhanced alpha-adrenergic and Ca2+ channel (verapamil)-dependent vascular tone probably contribute to the greater baseline FAVR in SS subjects on high NaCl. Failure to decrease vasoconstrictor responses to AII may indirectly contribute to their maladjustment of FAVR.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of adinazolam and diazepam, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers

Effects on psychomotor and cognitive performance of adinazolam (15 or 30 mg), alone and in combination with ethanol (0.8 g/kg), were studied in healthy male volunteers and compared to effects of 10 mg diazepam. Adinazolam 30 mg produced relatively long-lasting impairments on tests of tracking, attention, verbal and nonverbal information processing, and memory. Adinazolam 15 mg resulted in descreased visual information processing. Adinazolam decreased supine mean arterial pressure, but only the 15 mg resulted in a tendency for decreased plasma norepinephrine concentrations. After standing for 5 min, 30 mg adinazolam was associated with increased heart rate. Although ethanol consumption produced additive decrements on a continuous performance task, there was little evidence to support a synergistic effect. Adinazolam 30 mg was accompanied by increased self-reports of side effects, especially drowsiness.

Captopril modifies the hemodynamic and neuroendocrine responses to sodium nitroprusside in hypertensive patients.

To determine if clinically effective doses of the antihypertensive agent captopril affected the neuronal release of norepinephrine or baroreflex sensitivity, changes in plasma norepinephrine concentration and heart rate were related to the changes in mean arterial pressure seen during the intravenous infusion of stepwise incremental doses of sodium nitroprusside before and during captopril treatment in eight hypertensive men with normal or low plasma renin activity. At all times, significant linear correlations were found between the decrease in mean arterial pressure and the dose of sodium nitroprusside, the increase in heart rate and the decrease in mean arterial pressure, and the increase in plasma norepinephrine concentration and the decrease in mean arterial pressure. When the subjects were treated with captopril (25 mg t.i.d.) for 2 to 4 weeks, supine mean arterial pressure decreased from 130 to 114 mm Hg (-12%; p less than 0.05), heart rate did not change, supine and upright plasma renin activity increased, while supine plasma norepinephrine and epinephrine concentration decreased slightly. Therapy with captopril (25 mg t.i.d.) increased baroreflex sensitivity, as assessed by the slope of the regression line relating the increase in heart rate to the decrease in mean arterial pressure, and increased the responsiveness of the sympathetic nervous system, as assessed by the slope of the regression line relating the increase in plasma norepinephrine concentration to the decrease in mean arterial pressure. These increases were accompanied by a decrease in the slope of the regression line relating the decrease in mean arterial pressure to the dose of sodium nitroprusside and thus were associated with a decreased sensitivity to the vasodepressor effects of sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for a predominantly central hypotensive effect of alpha-methyldopa in humans.

We examined the time course and extent to which central and peripheral mechanisms contribute to the short-term effects of a 500-mg oral dose of alpha-methyldopa on supine mean arterial pressure, cardiac output, and total peripheral resistance, as well as its effects on total urinary excretion of norepinephrine and its metabolites, in five subjects with essential hypertension. Total peripheral resistance was reduced significantly 1 hour after alpha-methyldopa administration and remained so for the ensuing 7 hours of the study (p less than 0.05). A small but significant reduction in mean arterial pressure occurred 7 hours after the dose (p less than 0.05), while cardiac output did not change significantly. Total 24-hour urinary norepinephrine and metabolite excretion was reduced by 8.1 mumol (35% compared with placebo). The relative distribution of urinary norepinephrine metabolites was unaffected by alpha-methyldopa, and the catecholamine metabolites of alpha-methyldopa, alpha-methylnorepinephrine and alpha-methylnormetanephrine did not account for this reduction. Competitive inhibition of methyldopa transport across the blood-brain barrier and into the central nervous system by large oral doses of isoleucine antagonized most of the effect of alpha-methyldopa. The effects on total peripheral resistance were completely abolished, and small, insignificant changes during the 7-hour study were similar to those observed after placebo. Changes in mean arterial pressure were not significant; however, 24-hour total urinary norepinephrine and metabolite excretion increased by 6.1 mumol to 22.7 mumol (24.7 mumol excreted after placebo). Adding benserazide to the alpha/methyldopa-isoleucine dose regimen in an attempt to inhibit any residual, presumably peripheral, effects of alpha-methyldopa caused little, if any, further antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in Response of Black Hypertensives to Alpha vs. Beta Adrenergic Antagonists: Preliminary Findings

We tested our clinical impression that black hypertensives in our clinic population responded better to alpha-adrenergic blocking agents (clonidine and prazosin) than to beta-adrenergic blockers (atenolol, nadolol and propranolol). Compared to no effect from eight weeks of therapy with beta-blockers, clonidine significantly decreased erect mean arterial pressure (MAP) when assessed weekly for four weeks (p = 0.027 to 0.046). However, the decrease in supine MAP was not significant. The effects of prazosin were more modest. Supine MAP was significantly less than with beta-blockade (p = 0.032) at two weeks but not at four weeks and decrements in erect MAP were not significant. In this preliminary study, black hypertensives appeared to be more responsive to alpha-adrenergic antagonists than to beta-blockers, with clonidine more effective than prazosin. Elucidation of possible mechanisms of the difference and of its clinical importance warrant further study.

AUTONOMIC NERVOUS SYSTEM DYSFUNCTTION(AD)IN CHILDREN WITH END STAGE RENAL DISFASE: OOMPARISON OF HEMD-(HD) AND PFRTIONEAL(PD)DIALYSIS

Symptomatic hypotension complicated 53-87% of all treatments in 7 of our pediatric HD patients (HDP) despite modest ultrafiltration (<6% of estimated dry weight). The possible relationship of AD to this problem was evaluated in 12 dialysis patients (DP) aged 8.1-19.8 yrs, 5 of whom were receiving peritoneal dialysis(PDP),and in 7 controls (C) aged 8.0-16.5 yrs, using the heart rate (HR) response to the Valsalva Maneuver (VM) (straining to 40 mm Hg × 10 sec)and degree of beat-to-beat variability in the resting heart rate (BVHR). Studies were performed using a standard electrocardiograph; the Valsalva Ratio(VR)was calculated as the maximal RR interval following÷minimal RR interval during VM. BVHR was determined as the coefficient of variation(CV)of 150 successive RR intervals recorded during recumbency. All DP had normal cardiac function by echocardiography, and none had orthostatic hypotension. The mean VR for C (2.06±.23) was significantly higher than that for HDP(1.54±.19,p<.001),PDP (1.68±.18,p<.02),and the group as a whole (1.60±.19,p<.001). In most DP the abnormally low VR was due to a failure to develop adequate reflex bradycardia following the release of straining. The mean CV for C (.103±.034) was significantly higher than that for HDP (.042±.015,p<.001) but not PDP (.072±.015,p<.10). Moreover, the mean CV for HDP was significantly lower than that for PDP (p<.01). Mean hemoglobin concentrations were not significantly different in HDP (7.1±1.5 g/dl)vs. PDP(7.6±.94 g/dl,p>.40), nor were the observed disturbances attributable to differences in resting HR, supine mean arterial pressure,months on dialysis, or age. The data indicate that AD occurs commonly among pediatric DP. The observed pattern of disturbances is consistent with defective cardiac parasympathetic innervation, with HDP more severely affected than PDP. AD also may be 'unmasked' more readily in HDP, since the higher ultrafiltration rates associated with HD require more effective cardiovascular reflex compensation. AD should be considered as a possible cause of recurrent, symptomatic hypotension in pediatric DP.

The role of the renin-angiotensin system in the hormonal and renal responses to tilt in normal man.

Head-up tilt is associated with rapid increases in total peripheral and renal resistance and falls in the urinary excretion of water and sodium. The influence of the acute oral administration of the converting enzyme inhibitor captopril (50 mg) on the consequences 60 degrees head-up tilt were assessed in 6 normal subjects on unrestricted sodium intake. Captopril did not modify the responses of arterial pressure and heart rate to tilt, although a significant decrease in supine mean arterial pressure was induced by captopril. In addition, the agent blunted by 50-60% all the changes in renal hemodynamics and urinary excretion of water and electrolytes except for that of the fractional excretion of sodium. Urinary kallikrein activity which markedly fell and plasma aldosterone concentration which increased during tilt before captopril were not affected after administration of the drug. These studies indicate that angiotensin might mediate at least in part the renal hemodynamic and functional responses to tilt in normal man and is the primary determinant of the aldosterone stimulating effect of tilt.

Effects of beta-adrenoceptor agonists and antagonists in patients with peripheral autonomic neuropathy.

Abstract 1 Four patients with orthostatic hypotension due to peripheral autonomic neuropathy were studied. The diagnosis was based on severe hypotension during 60-degrees head-up tilting and absence of the systolic pressure overshoot in phase IV of the Valsalva response. Plasma noradrenaline levels were less than 25 pg/ml in two patients and between 50 and 90 pg/ml in the remainder. Noradrenaline was unresponsive to head-up tilting in all. Heart rate did not change after atropine, 1 mg i.v., in three patients. Thus all patients had a postganglionic efferent sympathetic lesion, which was associated with an efferent parasympathetic lesion in three. 2 After propranolol 16 mg i.v. and metoprolol 8 mg i.v., heart rate did not change. After incremental doses of pindolol heart rate rose in a dose-dependent way by a maximum of 18±3 beats/min at 1.6 mg i.v. 3 After treatment with pindolol, 15 mg daily divided in three doses, the patients, who were previously bedridden, were free of orthostatic symptoms and they were able to walk and stand without fainting. Before treatment intra-arterial pressure fell within 2 min from 115±8/58±6 mm Hg to 57±2/40±2 mm Hg after 60-degrees head-up tilting. During treatment supine arterial pressure was 142±9/81±5 mm Hg and all patients tolerated the tilting procedure for at least ten minutes while arterial pressure fell to 98±9/56±4 mm Hg. 4 The increase in supine mean arterial pressure from 72±4 to 102±4 mm Hg after 4 weeks treatment with pindolol was caused by a rise in cardiac output from 4.9±0.6 to 6.8±0.5 l/min. Calculated total peripheral resistance was unchanged. Heart rate had risen from 70±3 to 88±4 beats/min and stroke volume from 66±3 to 80±5 ml. 5 Infusion of isoprenaline in one of the patients showed supersensitivity for the chronotropic and vascular effects of this drug. Similar cardiac and vascular supersensitivity was observed for salbutamol. In this patient the isoprenaline dose-heart rate response curve was shifted to the right by a factor of 6, 72 h after discontinuation of pindolol. The salbutamol dose-heart rate response curve was shifted by a factor of 50. 6 These data illustrate the clinical applicability of the pharmacological principle of partial agonism; a pure antagonist has no effect and a partial agonist acts as a pure agonist when receptor occupancy is low. The observed chronotropic effects of salbutamol provide evidence for the existence of cardiac β2-adrenoceptors in man. Comparison between the cardiovascular responses to the non-selective β-adrenoceptor agonist isoprenaline and the β2-selective agonist salbutamol suggests preferential β2-adrenoceptor sensitisation in chronic autonomic failure, which can be reversed by treatment with the non-selective partial β-adrenoceptor agonist pindolol.

N"-Cyano-N-4-pyridyl-N'-1,2,2-trimethyl-propylguanidine, a new vasodilating agent: acute effect of blood pressure and pharmacokinetics in hypertensive patients.

N"-Cyano-N-4-pyridyl-N'-1,2,2-trimethylpropylguanidine (P 1134) is a new vasodilating antihypertensive compound. In an open study, P 1134 was given in single oral doses of from 10 to 25 mg to 12 previously untreated patients with essential hypertension. All patients responded with decreases in mean arterial pressure (MAP) of at least 10 mm Hg and with almost equal blood pressure decreases in the supine and erect position. The increase of dose was significantly correlated with a progressive reduction of blood pressure. At a dose of 25 mg, the maximal decrease in supine MAP averaged 38 mm Hg, and the maximal increase in heart rate averaged 23 beats/min. Peak effect and serum concentration were seen about 1 h after tablet intake. The serum half-life from the peak concentration averaged 2.5 h. It is concluded that P 1134 is a fast-acting, effective antihypertensive agent.

Essential hypertension: relationship between renin and blood pressure.

Supine (basal) plasma renin activity (PRA) and mean arterial pressure (MAP) were determined in 564 essential hypertensives grouped by age and sex. Mean supine PRA showed an age-dependent significant decrease (p < 0.001), whereas an increase in MAP was observed with age (p < 0.001). There were no sex-related differences both in PRA and MAP. In younger hypertensives (15-34 years) of both sexes an inverse correlation was obtained between PRA and MAP, whereas middle-aged men (35-50 years) and male and female hypertensives of older age (> 51 years) showed a positive relationship between these two parameters. No significant correlation was seen between PRA and MAP in middle aged women (35-50 years). The observed findings suggest a negative feed-back mechanism between blood pressure and renin release in younger hypertensives. In older patients this mechanism is disturbed probably through hypertension induced changes in the renovascular system resulting in an inappropriate large release of renin for a given level of blood pressure. This conversion from an inverse to a positive relationship between PRA and MAP occurred earlier in male than in female patients. Finally, our results support the assumption that in essential hypertension changes in renin secretion are rather the sequel than the cause of elevated blood pressure.

The outpatient treatment of refractory hypertension with minoxidil.

Minoxidil is a potent orally administered vasodilator under investigation for use in severe hypertension. Fifteen patients with moderate to severe hypertension refractory to conventional antihypertensive drugs were treated with minoxidil on an outpatient basis. Propranolol and furosemide were administered concomitantly to control reflex tachycardia and fluid retention. Good blood pressure control was achieved in all but one patient with the average supine mean arterial blood pressure falling from 140 mm Hg with conventional drugs to 106 mm Hg with minoxidil (P less than 0.0005). The major side effects of fluid retention (9/15), hirsutism (15/15), and tachycardia were adequately controlled in all but one patient. We conclude that minoxidil will be a valuable drug in the outpatient management of refractory hypertension.

EFFECTS OF TIMOLOL AND HYDROCHLOROTHIAZIDE ON BLOOD-PRESSURE AND PLASMA RENIN ACTIVITY Double-blind Factorial Trial

The effects of timolol (10 mg thrice daily) and hydrochlorothiazide (50 mg/day) have been compared in a double-blind factorial trial in 20 patients with essential hypertension. There were four randomised test phases of 8 weeks each during which patients received timolol alone, hydrochlorothiazide alone, timolol plus hydrochlorothiazide, and no treatment (placebo). Blood-pressure was measured weekly, alternately at the outpatient clinic and at the patient's home. Supine mean arterial pressure fell from 119 mm Hg in the placebo phase to 110 mm Hg in the hydrochlorothiazide phase, 106 mm Hg in the timolol phase, and 101 mm Hg in the combined timolol plus hydrochlorothiazide phase. Factorial analysis revealed that these effects of the two drugs were additive without any potentiation or antagonism. Mean plasma-renin activity (P.R.A.) was 5-02 ng/ml/3 h in the placebo phase falling to 1-79 in the timolol phase and rising to 9-54 in the diuretic phase, but remaining unchanged in the combined treatment phase (5-40 ng/ml/3 h). The data suggest that the hypotensive action of timolol is not dependent on the concomitant fall in P.R.A. The methods described provide a valuable tool for quantitating the effects of a given drug, and hence a valid basis for objective comparison.

Adrenergic regulation of blood pressure in chronic renal failure.

Previous investigations have suggested that significant hypotension during hemodialysis may result from abnormalities of sympathetic nervous system activity. To further evaluate these phenomena, plasma dopamine beta-hydroxylase (D beta H) and cold pressor test (proposed indexes of efferent sympathetic nervous system activity) and amyl nitrite inhalation (an index of the entire baroreceptor reflex arc) were studied in two groups of patients: group I, patients exhibiting a mean arterial pressure decrease to less than 70 mm Hg during less than 10% of dialyses; group II (hemodialysis hypotension), patients with a mean arterial pressure decrease to less than 70 mm Hg during more than 90% of dialyses. The groups were similar with respect to plasma renin activity, renin response to ultrafiltration, age, duration of dialysis, nerve conduction velocity, plasma protein concentration, hematocrit, dialysis weight change, resting heart rate, sex, race, blood pressure and heart rate response to cold pressor test, and 125I-albumin plasma volume. Supine mean arterial pressure was higher in patients with hemodialysis hypotension than in patients without hemodialysis hypotension (group I) both before and after dialysis. Plasma D beta H activity was significantly higher in patients with hemodialysis hypotension (group II) than in group I both before and after dialysis. Amyl nitrite inhalation, expressed as change in delta R-R interval/mean arterial pressure decrease, was less in hemodialysis hypotension patients. These results suggest that hemodialysis hypotension may result from a lesion in the baroreceptors, cardiopulmonary receptors, or visceral afferent nerves. Furthermore, elevated mean arterial pressure in patients with hemodialysis hypotension may be neurogenic in origin, as reflected by plasma D beta H activity, and appears similar to the hypertension that follows baroreceptor deafferentation of experimental animals.

Quantitative Effects of Timolol and Hydrochlorothiazide on Blood Pressure, Heart Rate and Plasma Renin Activity: Results of a Double-Blind Factorial Trial in Patients with Essential Hypertension

1. The anti-hypertensive actions of timolol and hydrochlorothiazide were analysed in a double-blind 2 x 2 factorial trial in twenty patients with essential hypertension. Each patient went through four phases of 8 weeks in randomized order, receiving timolol alone, hydrochlorothiazide alone, timolol plus hydrochlorothiazide, and placebo. 2. Supine mean arterial pressure fell from 119 mmHg in the placebo phase, to 110 mmHg during the thiazide phase, 106 mmHg during the timolol phase, and to 101 mmHg during the combined timolol plus hydrochlorothiazide phase. 3. Factorial analysis revealed that the hypotensive actions of the beta-receptor-blocking drug and the diuretic were additive, without any synergism or antagonism. 4. Plasma renin activity measured in ng 3 h-1 ml-1 rose from 5-02 in the placebo phase to 9-54 in the diuretic phase, but fell to 1-79 in the beta-receptor blockade. It was unchanged in the combined therapy phase, despite the greater drop in blood pressure. These results suggest that the fall in plasma renin activity during beta-receptor blockade is of little importance in the hypotensive action of beta-receptor-blocking drugs.

Haemodynamic and blood volume studies in long-term haemodialysis patients, and in patients with successfully transplanted kidneys.

1. Stabilized hypertensive haemodialysis patients, as well as those with normotension, had a greatly elevated cardiac index (CI) that was not due to hypervolemia, but was most likely secondary to their anaemic condition. The hypertension itself was not accompanied by hypervolaemia, but was associated with a relatively very high total peripheral resistance. 2. In eight patients with successfully transplanted kidneys the following results were found. (a) Five were clearly hypertensive and had supine mean arterial pressure between 117 and 143 mmHg. It is noted that they were receiving prednisone at the time of the studies. (b) CI was normal in seven. (c) Total blood volume was normal in all. (d) The presence of wide-open arterio-venous fistulae was not associated with an increase in CI.

METHYLDOPA AND HYDROCHLOROTHIAZIDE IN PRIMARY HYPERTENSION: CONTROLLED CLINICAL TRIAL OF DRUGS SINGLY AND IN COMBINATION.

Forty-five hypertensive patients were given hydrochlorothiazide for 1 month and were then allocated at random to one of three treatment groups: methyldopa and hydrochlorothiazide, methyldopa alone, or hydrochlorothiazide alone. Combination of hypotensive drugs reduced supine mean arterial pressure more effectively than methyldopa alone. Methyldopa and hydrochlorothiazide may have a slightly greater depressor effect on supine blood pressure than a thiazide alone, but the difference was not statistically significant in this study. Combination produced a significantly greater decrease in standing mean arterial pressure than did either drug alone. Pulse rate was modestly reduced in patients who received methyldopa. The mild increase in body weight after methyldopa alone was not seen in the other two groups. Serious toxicity was not observed in this short-term trial.

DOUBLE‐BLIND FACTORIAL TRIAL OF PRINDOLOL AND HYDROCHLOROTHIAZIDE IN HYPERTENSION

The antihypertensive actions of the beta-adrenergic blocking agent, prindolol, and of the diuretic, hydrochlorothiazide, were analysed in a double-blind randomized 2 X 2 factorial trial in 16 patients. There were four eight-week phases in which patients received prindolol alone, hydrochlorothiazide alone, prindolol plus hydrochlorothiazide in combination, and no treatment. Both drugs were given in fixed doses: prindolol, 10 mg three times per day; hydrochlorothiazide, 50 mg per day. Blood pressure was measured weekly, alternately at the outpatient clinic and at home. Supine mean arterial pressure (MAP) in resting patients fell from 127 mm Hg in the placebo phase to 117 mm Hg with hydrochlorothiazide alone, 116 mm Hg with prindolol alone, and 111 mm Hg with the combination of prindolol and hydrochlorothiazide. (The standard error of difference between treatments was +/-3-58). A mean factorial effect of -7 mm Hg for hydrochlorothiazide (P less than 0-01) and -8 mm Hg for prindolol (P less than 0-01) was obtained, and the two drugs acted in an additive manner. The effects on standing blood pressure in resting patients were similar. No serious side effects were noted.