15 patients (4 females, 11 males, 21 to 55-year old) with mild to moderate essential hypertension (EH) were treated with placebo for two weeks and thereafter with increasing doses of prindolol (15 to 38 mg/day in the mean) and kept on a mean maintenance dosage of 32 mg/day for an average of 16 weeks in all. Blood pressure (BP), heart rate und plasma noradrenaline (PNA) concentrations were measured under standardized conditions (supine, standing, walking) at the end of two weeks on placebo and after the experimental treatment period. The results were compared to those of a group of 15 normotensive untreated control subjects (NS): after an average of 16 weeks on prindolol BP fell from 163/113 mm Hg to 129/91 mm Hg in the mean. PNA levels in EH before prindolol were significantly higher than in NS (supine: 272 +/- 22.0 ng/l (mean +/- SEM) vs. 135 +/- 15.1 ng/l, standing: 448 +/- 31.9 ng/l vs. 359 +/- 18.4 ng/l, walking: 388 +/- 22.5 ng/l vs. 234 +/- 22.1 ng/l). In EH chronic administration of prindolol led to a significant decrease in PNA concentrations under all the three test conditions to levels which did not differ significantly any more from those derived from NS. The adrenergic response to upright posture reflected in the percentage increase in PNA was significantly less in EH before prindolol when compared to the percentage increase in NS. On prindolol the adrenergic response was not abolidhed, yet it tended to approach the values found in NS. Before prindolol under resting conditions diastolic BP correlated closely with the corresponding PNA levels (p less than 0.01, r = 0.66, n = 15). This correlation could not be reestablished after prindolol treatment. The decrease in PNA after long-term treatment with prindolol was not correlated to the fall in blood pressure. The decrease in PNA indicates a lower activity of the sympathetic nervous system which may contribute to the antihypertensive effect of prindolol.

1 Doses of clonidine 0.15 mg or guanfacine 1.0 mg, respectively, and 2 h later additional doses of clonidine 0.3 mg or guanfacine 2.0 mg, respectively, were given to 24 healthy students. 2 Blood pressure was reduced by the same amount by both drugs. 3 Plasma noradrenaline concentrations decreased with both drugs, but the reduction was significantly greater following the administration of clonidine. 4 Mental activity in the EEG was less suppressed in the guanfacine group than in the clonidine group. The differences were statistically significant. 5 Self-estimations for well-being and mood showed only small changes due to guanfacine but significant changes due to clonidine. 6 The decrease of information processing and the increase in reaction time, measured by performance in different psychometric tests, were significantly more pronounced after clonidine treatment than guanfacine. 7 A dose-response relationship could only be observed in vigilosomnograms, in the tests of selfestimation related to well-being and mood and in the decrease in plasma noradrenaline in the clonidine group. 8 It was concluded that guanfacine had a lesser CNS depressant action than clonidine, when administered in equipotent hypotensive doses.

1. Plasma noradrenaline was measured in fiftynine patients with mild to severe essential hypertension and in fifteen normotensive control subjects under basal and orthostatic conditions. 2. In patients with essential hypertension mean plasma noradrenaline concentrations were significantly higher than in control subjects under basal and orthostatic conditions. 3. In patients with essential hypertension basal diastolic blood pressure correlated closely with the corresponding plasma noradrenaline concentrations. 4. Long-term treatment with prindolol of patients with essential hypertension led to a significant fall in diastolic and systolic blood pressure and heart rate and to a significant decrease in plasma noradrenaline concentrations under basal and orthostatic conditions. 5. The adrenergic response to upright posture, reflected by an increase in plasma noradrenaline, was not abolished by prindolol. 6. It is concluded that the anti-hypertensive effect of prindolol in patients with essential hypertension is at least partially mediated by a decrease of sympathetic nervous activity.

1 The acute and chronic effects of guanfacine on blood pressure, plasma noradrenaline concentration and plasma renin activity were investigated in 23 patients (15 males, 8 females) with essential hypertension (WHO grade I-II). 2 Guanfacine induced a decrease in plasma noradrenaline concentration and plasma renin activity concomitant with a fall in blood pressure and heart rate in both the acute and the chronic study. 3 The adrenergic response to upright posture, reflected by an increase in plasma noradrenaline concentration and plasma renin activity, was not abolished after chronic guanfacine therapy. 4 The decrease in blood pressure 15 min after intravenous administration of guanfacine was inversely correlated with the basal sympathetic activity before treatment and with the decrease in plasma noradrenaline. 5 After chronic treatment with guanfacine no significant correlation existed between blood pressure reduction and the concomitant changes in peripheral sympathetic and/or plasma renin activity. 6 Despite the lack of a close correlation it is suggested that the antihypertensive effect of guanfacine in patients with essential hypertension is at least partially mediated by an inhibition of the sympathetic nervous and plasma renin activity.

Plasma nor-epinephrine (NE) and epinephrine (E) levels at rest and immediately after exercise were estimated in 8 patients with asymptomatic extrinsic allergic bronchial asthma. The patients had a normal airway resistance at rest and developed a marked bronchoconstriction (EIB) during exercise, which could be prevented by previous alpha-adrenergic blockade with phentolamine. In 7 control persons NE and E levels were measured also after beta-adrenergic blockade with propranolol. The following results were obtained: 1. At rest NE levels showed no significant differences between the groups. After exercise an increase of NE was observed in all groups, but in patients, even after phentolamine, and in normals after propranolol the increase was significantly higher than in the normal group within the control test. 2. No significant differences between the groups were found in E levels at rest and after exercise. Exercise caused no significant increase of E levels, except in the normals after propranolol application. 3. No significant correlation existed between NE levels and the increase of airway resistance after exercise. It is concluded that during exercise in asthmatics the sympathetic activity is enhanced, but the provocation of an EIB does not seem to be mediated by enhanced plasma NE levels.