Dietary sodium variation, erythrocyte cationic transport and plasma renin-aldosterone in men

Erythrocyte concentrations and fluxes of sodium and potassium were investigated in normal white male subjects during dietary sodium restriction and repletion, each period lasting for 16 weeks. Intraerythrocyte sodium concentration decreased and red cell ouabain-sensitive 86Rubidium-uptake increased during dietary sodium restriction while no significant changes were observed in the total, furosemide-resistant and furosemide-sensitive sodium-efflux and the sodium, lithium-countertransport. The decrease in intraerythrocyte sodium concentration could have resulted from the observed increase in sodium, potassium-ATPase pump activity. The latter increase could have been secondary to the early decrease in a digitalis-like plasma inhibitor and the later increase could have been facilitated by the late rise in the intracellular adenosine triphosphate concentration, which is the energy supplier for this pump. During the subsequent first month of sodium repletion intraerythrocyte sodium concentration remained low. Red cell ouabain-sensitive 86Rubidium-uptake and adenosine triphosphate concentration remained elevated and returned to baseline only after 16 weeks. This long-term effect suggests either the involvement of a mechanism which can only be slowly reversible or a mechanism which is irreversible so that normalization takes place only when new red cells are released into the circulation.     

What Can Precipitating Factors Teach us About the Pathogenesis of Migraine?

SYNOPSIS
Relationships between precipitating factors in the pathogenesis of migraine were studied in a sample of 217 migraineurs. The most frequently cited triggers were the menstrual cycle (51.5% of the women), alcoholic beverages (51.6%) and emotional or psychic stress (48.8%). Analysis of 4 subgroups of patients, i.e. those with only one of these 3 triggers or with none of these (controls), showed that alcohol-susceptible patients reported significantly (p<0.001) more alimentary triggers than the controls. A similar phenomenon was found in patients with menstrual-cycle related migraine, but in this group the difference with the controls fell short of reaching statistical significance. A further analysis showed that menstrual migraine attacks are more frequently preceded by depressive symptoms than other migraine attacks.
It is suggested that the gut of certain migraineurs may be unduly permeable, either intrinsically or extrinsically (e.g. under the influence of alcohol). In addition, in some patients with menstrual migraine, a depressive episode, associated with the menstrual period, may facilitate the development of a migraine attack.     

Inheritance of blood pressure and haemodynamic phenotypes measured at rest and during supine dynamic exercise.

Thirty-two pairs of monozygotic and 21 pairs of dizygotic male twins aged between 18 and 31 years were studied. Blood pressure was measured and Doppler echocardiography at the level of the aorta was performed in resting conditions and at two levels of supine submaximal bicycle exercise (at a fixed work load of 60 W and at a work load corresponding to a heart rate of 110 beats/min). In resting conditions, a genetic component in the variability of systolic and diastolic blood pressure was found; during submaximal supine exercise only a minor genetic effect was observed. At rest, genetic variance was shown for left ventricular outflow haemodynamics and for peripheral vascular resistance. However, during exercise, the transmissible effect on haemodynamics and peripheral resistance was small.     

Syst-Eur--a multicenter trial on the treatment of isolated systolic hypertension in the elderly: first interim report.

Syst-Eur is a multicenter placebo-controlled outcome trial designed by the European Working Party on High Blood Pressure in the Elderly to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension (ISH). Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mm Hg with a diastolic blood pressure less than 95 mm Hg. The present paper is an interim report on the first 316 patients randomized into this trial. The placebo (n = 170) and active treatment (n = 146) groups were similar at randomization with respect to age (73 +/- 8 years; mean +/- SD), sitting blood pressure (178 +/- 12 mm Hg systolic; 85 +/- 7 mm Hg diastolic), percentage of men (34%), and percentage of patients with cardiovascular complications (29%). After randomization blood pressure fell more (p less than 0.001) in patients on active treatment than in those in the placebo group (19 +/- 20 mm Hg systolic; 6 +/- 10 mm Hg diastolic vs. 7 +/- 19 and 1 +/- 10 mm Hg for sitting blood pressure). This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the two treatment groups can be achieved and maintained. New centers are being recruited in order to randomize a total of 3,000 patients.     

Postmarketing study of the use of flunarizine in vestibular vertigo and in migraine

Objective: This international postmarketing observational study of flunarizine was designed to evaluate, in routine clinical practice, the risk/benefit ratio of flunarizine in its approved indications, namely prophylaxis of migraine and treatment of vertigo. Comparator drugs were propranolol in migraine and betahistine in vertigo. The study was carried out by 498 general practitioners in Belgium, The Netherlands and Germany, whose participation had been requested by mail. In total 3186 patients were entered: 1601 in the two migraine cohorts and 1585 in the two vertigo cohorts. Results: In the migraine study, treatment results with propranolol tended to be somewhat better than those with flunarizine, but a selection bias cannot be excluded. There was no clear difference regarding efficacy between flunarizine and betahistine in the vertigo study. The safety evaluation focused on extrapyramidal symptoms (EPS) and depression. Overall, EPS were noted in only four patients, two in the vertigo-betahistine and two in the migraine-flunarizine cohort. A total of 70 patients developed depressive symptoms (34 in the flunarizine and 24 in the propranolol migraine cohorts, but only 7 in the flunarizine and 5 in the betahistine vertigo cohorts). Patients with migraine were clearly more prone to depression than patients with vertigo, regardless of their treatment. Additional risk factors for depression were a history of depression, and, in the migraine flunarizine cohort, a high number of previous migraine treatments. Received: 23 October 1995/Accepted in revised form: 20 February 1996     

Humoral and cellular effects of the K+-channel activator cromakalim in man

Summary The effect of cromakalim, a K⁺-channel activator, on the plasma renin-angiotensin-aldosterone system, catecholamines and -atrial natriuretic peptide, and on the intraerythrocyte concentration and transmembrane fluxes of Na⁺ and K⁺ has been investigated in 18 normal male subjects, in a double-blind parallel study. After a run-in period on placebo for 1 week, the subjects were treated either with placebo (n=6) or cromakalim (n=12) for 1 week.Plasma renin activity was significantly increased during cromakalim. No effect of cromakalim on plasma angiotensin II, aldosterone, adrenaline, noradrenaline and -atrial natriuretic peptide was demonstrated. The intra-erythrocyte K⁺ concentration was decreased during cromakalim administration and Ca²⁺-dependent K⁺-channels in red blood cells were increased.     

Haemodynamic response to graded exercise during chronic beta-adrenergic blockade with bunitrolol,an agent with intrinsic sympathomimetic activity

Summary The effect of chronic beta blockade on the haemodynamic response to graded exercise was studied in 18 hypertensive patients treated with bunitrolol, which has partial agonist activity. The patients first received a placebo for 5 to 12 days, then bunitrolol 30 mg daily for one week and subsequently the dose was doubled weekly as necessary upto 240 mg daily. At rest haemodynamic changes after beta blockade were only minor; heart rate decreased by 8% and no significant change was observed in stroke index, cardiac index, (a-v)O₂ difference and VO₂. The hypotensive effect was not significant and no significant change in mean pulmonary arterial and wedge pressure was observed. Maximal exercise capacity remained unchanged, because of haemodynamic responses. The maximal exercise heart rate was reduced by 25% during beta blockade, which was compensated by a 34% elevation in stroke index, whereas maximal cardiac index and (a-v)O₂ difference remained unchanged. There was no consistent change in mean pulmonary artery pressure during maximal exercise, but the mean brachial artery pressure fell by 12%.