Naoki Sano

FUNCTIONAL RELATIONSHIPS BETWEEN PLATELET ALPHA2-ADRENOCEPTORS AND SYMPATHETIC NERVE ACTIVITY IN CLINICAL HYPERTENSIVE STATES

Tritiated yohimbine binding was used to estimate platelet membrane alpha 2-adrenoceptor characteristics in normal subjects (n = 12) and patients with essential hypertension (n = 30), primary hyperaldosteronism (n = 10) and phaeochromocytoma (n = 10). There was a 20-fold increase in mean levels of resting norepinephrine and epinephrine in the phaeochromocytoma group. Total binding sites (Bmax) and dissociation constant (Kd) for 3H-yohimbine did not differ significantly among the four groups. Following curative surgery for phaeochromocytoma, plasma catecholamine levels were normalized but the Bmax remained unchanged. Following surgery for primary hyperaldosteronism, levels of plasma norepinephrine rose but Bmax was not changed. In all but the phaeochromocytoma patients, Bmax values correlated positively (r = 0.437, n = 48, P less than 0.01) with resting plasma norepinephrine. A significant negative correlation was observed between the change in plasma norepinephrine in response to postural change and resting Bmax. Treatment for 2-4 weeks with guanabenz or bethanidine induced a parallel fall in both Bmax and plasma norepinephrine. Treatment with reserpine was followed by a comparable fall in plasma norepinephrine, but Bmax values were unchanged. The findings support the view that platelet alpha 2-adrenoceptor density is functionally regulated in parallel with sympathetic nerve activity rather than circulating catecholamine levels, although it is not known which neuronal substance(s) may participate in this regulation.

PLASMA FREE DOPAMINE IN HUMAN HYPERTENSION

The concentration of plasma free dopamine (PDA) is said to be much lower than that of other catecholamines and its physiological significance remains unclear. Our recent studies using a newly developed radioenzymatic method disclosed the fairly distinctive features of PDA in patients with various types of hypertension. PDA was also confirmed as a variable responsive to postural change, dietary sodium loading and dopamine receptor antagonist. The results suggest that PDA could be a sensitive marker to represent the peripheral dopaminergic function, which might play an inherent role as a physiological regulator responsible for the cardiovascular and endocrine system.

A sympathetic component of baroreflex function in patients with essential hypertension.

1 The baroreflex‐mediated changes in plasma norepinephrine (NE) and heart period (RR interval) to phenylephrine (PE)‐evoked pressor and nitroprusside (NP)‐evoked depressor stimulations were studied in 19 patients with chronic essential hypertension, 12 with borderline hypertension and in 11 age‐matched normal controls. 2 Intravenous infusion of PE at a rate of 0.25‐1.0 |ig/kg/min induced dose‐related increases in fhean arterial pressure (MAP) and in RR interval and a decrease in plasma NE. Similarly, NP infusion at a rate of 0.1‐0.4 ug/kg/min evoked the opposite changes in each variable. The reflex sensitivity was defined as the slope of linear regression between the changes in RR interval and MAP (RR/MAP) and between those in plasma NE (% of the baselines) and MAP (%NE/MAP). 3 Both RR/MAP and %NE/MAP for pressor and depressor stimulations were reduced below values found in normal subjects, in both chronic and borderline hypertensives. 4 The values of %NE/MAP was negatively related to the basal plasma NE during falls in blood pressure (r= ‐0.401, P<0.05). 5 The %NE/MAP may be a useful index of the sympathetic component of baro‐reflex sensitivity. A decrease in %NE/MAP in hypertensive and borderline hypertensive patients suggests a blunted sensitivity of the sympathetic constrictor reflexes.

Functional Relationship Between Platelet α2-Adrenoceptors and Sympathetic Nerve Activity in Man

Functional relationships between platelet α2-adrenoceptors and sympathetic nerve activity were studied in patients with essential hypertension (n=23), primary aldosteronism (n=10), and normal subjects (n=12). The maximum number of binding sites (Bmax) and the dissociation constant (Kd) of 3H-yohimbine on platelet membranes and resting plasma norepinephrine (NE) were similar among these groups of subjects. In all subjects combined, Bmax values were correlated positively (r=0.471, p<0.01) to resting plasma NE and negatively (r=-0.531, p<0.01) to the changes in plasma NE when subjects were moved from lying to standing. A 2–4 week treatment with guanabenz or bethanidine induced a parallel fall of both Bmax and plasma NE, whereas administration of reserpine caused a similar fall of plasma NE but Bmax remained unchanged. Kd values were not changed after any of these treatments.The results support the view that platelet α2-adrenoceptor density is functionally regulated in parallel with sympathetic nerve activity...