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1. Brain natriuretic peptide, closely related to atrial natriuretic peptide in structure, may be an important circulating hormone. Its physiological role is unclear. First, we studied the effects of incremental infusions of brain natriuretic peptide in six healthy men on plasma brain natriuretic peptide levels and the pharmacokinetics of brain natriuretic peptide. Synthetic human brain natriuretic peptide-32 was infused intravenously, at an initial rate of 0.4 pmol min-1 kg-1, doubling every 15 min until the dose rate reached 6.4 pmol min-1 kg-1, at which rate the infusion was maintained for 30 min. 2. The brain natriuretic peptide infusion raised the brain natriuretic peptide-like immunoreactivity from 1.4 +/- 0.5 pmol/l to 21.4 +/- 7.6 pmol/l. Brain natriuretic peptide-like immunoreactivity after the end of infusion was consistent with a bi-exponential decay, with half-lives of 2.1 min and 37 min. 3. Next, we studied the effects of low-dose infusion of brain natriuretic peptide to mimic physiological increments in the circulating levels in comparison with atrial natriuretic peptide. Six dehydrated male subjects received intravenous infusions of atrial natriuretic peptide and brain natriuretic peptide, separately and in combination, in a randomized double-blind, placebo-controlled, four-part cross-over design. Atrial natriuretic peptide and brain natriuretic peptide were given at the rate of 0.75 and 0.4 pmol min-1 kg-1, respectively, for 3 h. The control infusion consisted of the vehicle. 4. Analysis of variance showed that atrial natriuretic peptide and atrial natriuretic peptide plus brain natriuretic peptide, but not brain natriuretic peptide alone, increased urinary flow and decreased urinary osmolality significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent guidelines on management of hypertension may unwittingly have focused some attention on the question of when treatment should start in younger patients. Although younger patients have a high relative risk of premature vascular disease,' they gain little from treatment in short term studies. The implication from the Medical Research Council trials of treatment in hypertension2' and the British Hypertension Society guidelines4 is that the cut off point for treatment falls from a diastolic blood pressure of 100 mm Hg in younger patients without coexistent risk factors to one of 90 mm Hg in elderly patients (see figure). Since general practitioners manage most patients with hypertension we investigated whether current practice mirrors existing guidelines and, in particular, whether the cut off point for treatment changes with patient age. Subjects, methods, and resultsQuestionnaires, endorsed by the British Hypertension Society and identified by number only, were sent to 200 of the 1145 general practitioners in East Anglia in May 1993. This sample was randomly selected. Follow up included a thank you or reminder letter and a second questionnaire to non-responders. General practitioners were asked the lowest systolic blood pressure they would use to define hypertension, the lowest diastolic pressure to define mild hypertension, and the lowest diastolic and systolic pressures at which they would start drug treatment for three age groups: less than 45, 45-65, and greater than 65. One hundred and twenty five (62-5%) completed questionnaires were returned. Results are expressed as means (95% confidence intervals). We used the STATGRAPHICS computer package to examine the influence of patients' age on the cut off points for defining and treating hypertension in a two way analysis of variance. The cut off points for definition and treatment were compared by repeated measures analysis of variance, incorporating the differences at each age group, and by paired t test at each age.The cut off points for systolic and diastolic blood pressure for both definition and treatment rose significantly with age in all three groups (P <0-0001 by two way analysis of variance; figure), but only 64 general practitioners treated isolated systolic hypertension. The cut off points for systolic pressure were 10-9 mm Hg (9 3 to 12-5 mm Hg) higher for treatment than for diagnosis; those for diastolic pressure were 3 8 mm Hg (3 3 to 4-2 mm Hg) higher for treatment than for diagnosis (p <0.0001 for both). Age did not affect the difference between these cut offpoints. CommentThere is an age paradox in the treatment of hyper- We thank the participating general practitioners; Dr C R Palmer for his statistical advice; Dr C J Garratt for his helpful comments; and Miss C Molton for all her computing advice.

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