Concentration effect relationships of infused histamine in normal volunteers.

Histamine was infused in six normal volunteers at rates of 16, 32, 64 and 96 ng/kg/min increasing at 5-min intervals followed by 128 ng/kg/min for 45 min. Heart rate increased, diastolic blood pressure decreased and skin temperature increased in a dose-dependent fashion. Mean heart rate increased by 15.6 +/- 5.7 beats/min, mean diastolic pressure fell by 8.8 +/- e.2 mmHg and mean skin temperature increased by 1.2 +/- 0.3 degrees C at the highest infusion rate. Mean plasma histamine rose from a basal level of 0.20 +/- 0.03 ng/ml to 1.97 +/- 0.25 ng/ml at the end of the highest infusion rate. The threshold infusion rate for physiological effects was 64-96 ng/kg/min corresponding to 0.77-0.97 ng/ml. Salivary flow was stimulated by 21% after 30 min at the highest dose infusion (P = 0.05). Plasma adrenaline increased 132% but plasma noradrenaline was unchanged. There was a linear decline in heart rate after terminating the histamine infusion with a half time of 82 sec. The half life of infused histamine in the plasma was 102 sec. The clearance of histamine from the plasma was 6.1 %/- 0.2 l/min or 83 ml/kg/min. These concentration effect relationships in normals throw doubt on some of the high endogenous plasma histamine values in the literature.

Estimation of sympathetic activity in essential hypertension.

The estimation of sympathetic nervous activity by measurement of plasma norepinephrine (NE) concentration assumes a constant relation between this and the synaptic cleft concentration. This assumption would be incorrect if the clearance of plasma NE could be varied without affecting its removal from the synaptic cleft, so we compared the clearance of plasma NE in mild hypertensives and normal subjects by measurement of its plasma concentration during a 0.5-hr infusion at 0.07 microgram/kg/min; there were no differences. The simultaneous infusion of isoproterenol, 0.02 microgram/kg/min, led to an increase in heart rate and NE clearance. There was partial inhibition of catechol-O-methyltransferase by a single oral dose of alpha-methyldopa, 250 mg, which reduced the clearance of both catecholamines (CAs) by about 20%. After the end of the infusions containing isoproterenol, the tachycardia persisted for more than 1 hr and declined more slowly in the hypertensives than the normals. In contrast, plasma concentrations of both CAs returned to basal values within a few minutes. The persistent tachycardia may be due to rerelease of isoproterenol into the synaptic cleft, since stimulation of sympathetic activity by assumption of the erect posture was associated with an exaggerated increase in heart rate (by 48/min after infusion and 23/min before infusion). The study therefore suggests that synaptic cleft and plasma CA concentrations can be independently manipulated and the relation between them may be different in hypertensive patients and normal control subjects.