1 Angiotensin converting enzyme inhibitors reduce blood pressure without reflex tachycardia, possibly as a result of enhanced hypothesis that this results from the removal of the parasympathetic activity. We examined the vagolytic action of angiotensin II or alternatively by acetylcholinesterase inhibition.2 Both captopril and [Sar1ala8] angiotensin II, (saralasin), caused modest falls in blood pressure, without increasing heart rate in normotensive subjects. 3 Captopril and saralasin significantly attenuated the vagally mediated heart rate slowing after facial immersion in water. There was a close correlation between the effects produced by captopril and saralasin on the diving reflex. 4 Infusion of subpressor doses of angiotensin II, reversed the hypotensive effect of captopril and returned the bradycardia after facial immersion to placebo level. 5 In vitro neither captopril nor enalapril or lisinopril affected bovine erythrocyte acetycholinesterase activity. 6 The parasympathetic effect of angiotensin converting enzyme inhibitors appear to reflect a direct consequence of the removal of angiotensin II.Keywords angiotensin converting enzyme inhibitors heart rate angiotensin II acetylcholinesterase parasympathetic effect

1 The effects of the orally active angiotensin converting enzyme inhibitor, captopril, were examined in 15 patients with mild or moderate essential hypertension. 2 Following initial dosing with captopril 25 mg, there was a significant fall in supine and erect blood pressure in 2 h and lasting for 6 h. There was no significant alteration of heart rate. No reduction was seen in plasma noradrenaline concentration. Maximum inhibition of plasma converting enzyme activity occurred 60 min post‐dosing. 3 There was a strong positive correlation between blood pressure reduction and converting enzyme inhibition. The magnitude of the blood pressure reduction and converting enzyme inhibition following initial dosing was reflected in subsequent success with captopril monotherapy during a 12 week follow‐up period. 4 It was also found that patients who did not achieve adequate blood pressure control on captopril in doses of 50 mg three times daily or less still were not controlled on a dose of 150 mg three times daily without the addition of a diuretic. 5 The risks of renal and marrow toxicity from captopril may be reduced by administering only low doses with the addition, where necessary, of a thiazide diuretic.

1 Calcium antagonists reduce myocardial contractility in vitro. Nicardipine is a dihydropyridine derivative with enhanced selectivity for vascular smooth muscle. 2 We have studied the pharmacokinetics and the haemodynamic effects that occur in man following bolus intravenous administration of nicardipine. 3 Ten normotensive male subjects received either nicardipine or placebo i.v., allocated in a randomised double-blind manner, over 60 s 4 Plasma nicardipine concentration, blood pressure, heart rate, and systolic time intervals were measured before dosing and at frequent intervals between I and 360 min post dosing. 5 At 160 jug kg-', adequate plasma levels of nicardipine were obtained to permit analysis of individual pharmacokinetic variables, and significant and consistent haemodynamic effects were seen. 6 After injection ofnicardipine, systolic BP and the QS2 (measure of total electromechanical systole) and QT intervals were not altered. 7 The changes in BP and heart rate were consistent with arteriolar vasodilatation. 8 The changes in PEP and LVET suggest an increase in cardiac contractility, which is unlikely to be a direct effect of nicardipine on the myocardium but rather a result of afterload reduction. 9 The close correlation of nicardipine plasma level with haemodynamic effect should permit accurate dose titration. 10 The net increase in contractility should allow nicardipine to be administered safely with fi-adrenoceptor blocking drugs.Keywords blood pressure calcium antagonist heart rate nicardipine systolic time intervals concentration effect modelling

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associated-as is now becoming apparent. Indeed, the situation with regard to both B27 and B5 associations may vary in different parts of the world. In our patients with Behqet's triad, two out of four are B5 positive and one out of four is B27 positive. Of those with "definite" Behqet's disease (by the criteria of Mason and Barnes5), two out of 11 are B5 positive and only one out of 11 is B27 positive. The connection with the B5 antigen seems less strong than in Turkey but further work is necessary to clarify the position. The criteria of Mason and Barnes are valuable in indicating some measure of diagnostic certainty. Patients with the triad of symptoms undoubtedly have Behqet's syndrome. But some patients satisfy their criteria at the "definite" level without the concurrence of mouth and genital ulceration which I would now regard as obligatory. Nor would I attach much importance to the presence or absence of a family history. Thus the stated prevalence rate of 0 064 per 10 000 can be only an estimate of the disorder's prevalence: it may be a slight overestimate. In any event it contrasts markedly with the Japanese finding of 1 in 10 000.6

Developmental screening of preschool children SIR,-I was intrigued by the article by Dr D J G Bain on "Methods used by general practitioners in developmental screening of preschool children" (6 August, p 363) in its revelation of such free-for-all methodology. "Examination forms," "visual charts," "alternative screening forms"-you think of it, the examining doctors choose it. Why are they