OBJECTIVE--To determine whether the reduction in blood pressure achieved in trials of dietary salt reduction is quantitatively consistent with estimates derived from blood pressure and sodium intake in different populations, and, if so, to estimate the impact of reducing dietary salt on mortality from stroke and ischaemic heart disease. DESIGN--Analysis of the results of 68 crossover trials and 10 randomised controlled trials of dietary salt reduction. MAIN OUTCOME MEASURE--Comparison of observed reductions in systolic blood pressure for each trial with predicted values calculated from between population analysis. RESULTS--In the 45 trials in which salt reduction lasted four weeks or less the observed reductions in blood pressure were less than those predicted, with the difference between observed and predicted reductions being greatest in the trials of shortest duration. In the 33 trials lasting five weeks or longer the predicted reductions in individual trials closely matched a wide range of observed reductions. This applied for all age groups and for people with both high and normal levels of blood pressure. In people aged 50-59 years a reduction in daily sodium intake of 50 mmol (about 3 g of salt), attainable by moderate dietary salt reduction would, after a few weeks, lower systolic blood pressure by an average of 5 mm Hg, and by 7 mm Hg in those with high blood pressure (170 mm Hg); diastolic blood pressure would be lowered by about half as much. It is estimated that such a reduction in salt intake by a whole Western population would reduce the incidence of stroke by 22% and of ischaemic heart disease by 16% [corrected]. CONCLUSIONS--The results from the trials support the estimates from the observational data in the accompanying two papers. The effect of universal moderate dietary salt reduction on mortality from stroke and ischaemic heart disease would be substantial--larger, indeed, than could be achieved by fully implementing recommended policy for treating high blood pressure with drugs. However, reduction also in the amount of salt added to processed foods would lower blood pressure by at least twice as much and prevent some 75,000 [corrected] deaths a year in Britain as well as much disability.

https://www.bmj.com/content/bmj/302/6780/819.full.pdf

By how much does dietary salt reduction lower blood pressure? III--Analysis of data from trials of salt reduction.

Since it became clear that K+ shifts with exercise are extensive and can cause more than a doubling of the extracellular [K+] ([K+]s) as reviewed here, it has been suggested that these shifts may c...

https://www.physiology.org/doi/pdf/10.1152/physrev.2000.80.4.1411

Dynamics and Consequences of Potassium Shifts in Skeletal Muscle and Heart During Exercise

Captopril is an orally active inhibitor of angiotensin-converting enzyme (ACE) and has been widely studied in the treatment of patients with mild to moderate essential hypertension, severe hypertension not responsive to conventional diuretic/beta-adrenoceptor blocker/vasodilator regimens, and patients with chronic congestive heart failure refractory to treatment with a diuretic and digitalis. In patients with mild or moderate essential hypertension, titrated low doses of captopril used alone or in conjunction with a diuretic are similar in efficacy to usual doses of hydrochlorothiazide, chlorthalidone, or beta-adrenoceptor blocking drugs, as well as to the other ACE inhibitors. In addition, captopril improved well-being to a greater extent than methyldopa or propranolol in a study designed specifically to determine the effect of treatment on the quality of life of patients with mild or moderate essential hypertension. The earlier demonstrated efficacy of captopril, used with a diuretic and often also with a beta-adrenoceptor blocking drug, in the treatment of severe hypertension refractory to conventional 'triple therapy' has been confirmed in more recent trials which illustrate the generally marked antihypertensive effect of captopril-containing regimens in such patients. Results of initial trials in patients with scleroderma are promising, with control of hypertension and stabilization of renal function in these patients when treated at an early stage of the disease. Several comparative and long term trials of captopril in patients with chronic congestive heart failure refractory to treatment with a diuretic/digitalis regimen clearly demonstrate that initial haemodynamic improvement is maintained and correlates with clinical benefit. A tendency for overall clinical response to captopril to be better than the response to prazosin, hydralazine, nisoldipine or enalapril has been reported. Results of a multicentre comparison with digoxin and placebo indicate that captopril is a suitable alternative to digoxin in patients with mild to moderate heart failure who are receiving maintenance diuretic therapy. The tolerability of captopril has now been studied in many thousands of patients involved in formalized trials and the early impression of poor tolerability can no longer be justified. The use of generally lower dosages of captopril in patients with normal or slightly impaired renal function has resulted in a generally low incidence of rash (0.5 to 4%), dysgeusia (0.1 to 3%), proteinuria (0.5%), neutropenia (0.3% during first 3 months) and symptomatic hypotension (0.1 to 3%). Cough is an infrequent but troublesome effect resulting from ACE inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Captopril. An update of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure.

Angiotensin-converting enzyme (ACE) inhibitors are widely used for controlling hypertension. Their use in women who are pregnant is not without risk to the fetus. We describe three infants exposed in utero to ACE inhibitors who had adverse outcomes. These cases, combined with other reports in the literature, suggest strongly that these drugs are fetotoxic. ACE inhibitor fetopathy is characterized by fetal hypotension, anuria-oligohydramnios, growth restriction, pulmonary hypoplasia, renal tubular dysplasia, and hypocalvaria. Although the true frequency of adverse fetal effects has yet to be determined, because of the debilitating and lethal nature of the fetal damage when it occurs, it is our recommendation that ACE inhibitors not be used in pregnancy, particularly in the second and third trimesters.

Angiotensin-converting enzyme inhibitor fetopathy.

Cette etude discute l'importance des differentes arythmies ventriculaires provoquees au cours de la stimulation electrique programmee (SEP) et leur rapport avec l'agressivite du protocole de SEP, le choix du protocole de stimulation, l'identification du patient a haut risque de mort subite apres un infarctus du myocarde

Programmed electrical stimulation of the heart in patients with life-threatening ventricular arrhythmias: what is the significance of induced arrhythmias and what is the correct stimulation protocol?

Ketanserin (120 mg/day) or placebo was given orally to 14 patients with mild to moderate essential hypertension according to a double blind crossover protocol, each treatment period lasting six weeks. Resting intra-arterial pressure in the recumbent position was reduced from 150/84 to 141/77 mm Hg; the hypotensive effect persisted throughout an uninterrupted graded exercise test to the point of exhaustion. The haemodynamic effects were similar at rest and during exercise. Overall, systemic vascular resistance decreased by 14%, heart rate fell by 5%, but stroke volume and cardiac output increased. Mean pulmonary arterial pressure and capillary wedge pressure were not significantly affected, but pulmonary vascular resistance decreased by 15%. The pressor response to methoxamine was significantly reduced by ketanserin. Both plasma noradrenaline and adrenaline concentrations increased, plasma renin activity and angiotensin II concentration decreased, and plasma aldosterone concentration was unchanged. The data indicate that ketanserin induces arteriolar dilatation, possibly related to an alpha-1-antagonistic action and to a reduced circulating angiotensin II concentration. The haemodynamic response is complex, and an increase in cardiac output limits the hypotensive effect. There is no firm evidence of an effect on venous tone as cardiac filling pressures do not change.

https://heart.bmj.com/content/heartjnl/51/2/149.full.pdf

Haemodynamic and humoral responses to chronic ketanserin treatment in essential hypertension.

Captopril during pregnancy

Ketanserin (3 X 40 mg daily) was administered during 6 weeks in 14 patients with mild to moderate essential hypertension using a double-blind, placebo-controlled, crossover design. Ketanserin decreased (p less than 0.01) the recumbent blood pressure from 159/104 to 153/97 mm Hg and the recumbent heart rate from 75 to 72 beats/min. Platelet aggregation induced by 5-hydroxytryptamine (5-HT), whether or not amplified by threshold doses of collagen, was not inhibited; however, it was reduced in 10 normal volunteers after a single oral dose of 40 mg ketanserin. The results suggest that long-term treatment with ketanserin reduces blood pressure; whereas 5-HT receptor inhibition could not be demonstrated when assessed by platelet aggregation.

Antihypertensive action and serotonin-induced platelet aggregation during long-term ketanserin treatment in hypertensive patients.

After 30 min rest in the lying position, 12 healthy male volunteers (average age 22 years) received, in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg iv followed by a continuous infusion of 10 mg/hr). Thereafter they rested for a further 30 min in the recumbent position and for 15 min sitting on a bicycle ergometer; they then exercised to exhaustion. At rest plasma levels of adrenocorticotropin (ACTH), cortisol, and aldosterone increased during infusion of naloxone, while body temperature decreased. During exercise the difference in plasma ACTH between naloxone and saline periods was abolished, while the differences in plasma cortisol and aldosterone lost statistical significance. Intra-arterial pressure, heart rate, ventilation, O2 uptake, and CO2 output were continuously monitored throughout the experiment and were not affected by naloxone. This was also the case for several hormonal and biochemical measurements, including those of plasma renin, angiotensin II, norepinephrine, 13,14-dihydro-15-keto-prostaglandin F2 alpha, glucose and lactate, and serum insulin and growth hormone. Exercise performance was not changed by naloxone. In conclusion (1) during exhaustive graded exercise of short duration opioidergic inhibition of the pituitary-adrenocortical axis is probably not sustained, (2) apart from the latter mechanism, the present study does not support the hypothesis that endogenous opioids are involved in various hemodynamic, respiratory, and hormonal responses to this type of exercise.

R Fiocchi

Papers

Haemodynamic and humoral responses to chronic ketanserin treatment in essential hypertension.

Captopril during pregnancy

Antihypertensive action and serotonin-induced platelet aggregation during long-term ketanserin treatment in hypertensive patients.

The nature of opioid involvement in the hemodynamic respiratory and humoral responses to exercise.

Progressive attenuation of the carotid baroreflex control of blood pressure and heart rate during exercise