1 The effect of guanfacine (2 mg once daily) on ambulatory blood pressure was studied with the Remler M 2000 recorder in 16 elderly hypertensive patients during a randomized, double-blind, placebo-controlled, balanced, cross-over study. 2 Guanfacine significantly reduced heart rate and systolic and diastolic ambulatory blood pressure. The antihypertensive effect was maintained over the whole recording period. 3 Systolic and diastolic blood pressure variability was not changed by guanfacine, neither when defined as standard deviation or variation coefficient of the mean, nor when defined as the range between the highest and lowest ambulatory blood pressure, suggesting that blood pressure variability is unrelated to sympathetic nervous system activity.

1 The effect of local administration of the dopamine2 (DA2)-receptor agonist quinpirole and of the DA,-receptor agonist fenoldopam was studied in the in situ, constant flow autoperfused, superior mesenteric vascular bed of the rat.2 Local infusion of quinpirole (30 pg kg-'min-' for 5min) had no effect on baseline perfusion pressure; it reduced the pressor responses to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) of the periarterial sympathetic nerves to 45.6 ± 2.1% of its original value but did not modify similar pressor responses produced by locally administered noradrenaline.3 The inhibitory effect of quinpirole was antagonized by the selective DA2-receptor antagonist domperidone (10 pg kg-') but not by the selective DA,-receptor antagonist SCH 23390 (50 pg kg-'). 4 Local infusion of fenoldopam (30 pg kg-' min-' for 5 min) reduced baseline perfusion pressure to 89.9 ± 1.9%, increased the pressor response to electrical stimulation (4Hz, 1 ms, supramaximal voltage) of the periarterial nerves to 134.7 ± 14.0%, but reduced the pressor response to locally administered noradrenaline to 37.2 ± 8.2%. Similar pressor responses induced by the selective a,-adrenoceptor agonist phenylephrine were also reduced by fenoldopam (to 38.4 ± 6.4%), but responses to locally administered angiotensin II were not modified.5 Pretreatment with SCH 23390 (50 pg kg-') antagonized the effect of fenoldopam on baseline perfusion pressure, but had no influence on the effect of fenoldopam on responses to electrical stimulation or to noradrenaline.6 Pretreatment with the selective az-adrenoceptor antagonist rauwolscine (100 pg kg-') had no effect on the reduction in baseline perfusion pressure induced by fenoldopam nor on its inhibitory effect on the response to noradrenaline, but it antagonized the stimulatory effect of fenoldopam on the response to electrical stimulation.7 The results show that quinpirole inhibits neurogenic vasoconstriction in the rat superior mesenteric vascular bed through stimulation of presynaptic DA2-receptors while fenoldopam stimulates postsynaptic vasodilatory DA,-receptors. In addition, our results suggest that the inhibitory effect of fenoldopam on the vasoconstrictor response to noradrenaline may be due to an antagonistic action at postsynaptic a,-adrenoceptors, while its potentiating effect on neurogenic vasoconstriction is due to blockade of presynaptic oi2-adrenoceptors.

Chronic administration of nadolol has been reported to reduce blood pressure either without or with a concomitant fall of renal blood flow. We therefore studied the effects of nadolol 80 mg once daily on ambulatory blood pressure, renal and systemic haemodynamics in patients with mild to moderate essential hypertension. Ten patients took part in this randomized, double‐blind, placebo‐controlled, crossover study, each phase of which lasted 4 weeks. Nadolol significantly reduced ambulatory blood pressure and heart rate, but had no effect on blood pressure variability. Cardiac output was significantly reduced by nadolol and total peripheral resistance increased but without reaching statistical significance. Despite the fall in blood pressure and cardiac output, renal blood flow and glomerular filtration rate remained unchanged. The fraction of cardiac output reaching the kidneys rose significantly and renal vascular resistance was significantly reduced. Body weight, urinary sodium excretion and urine flow rate remained unchanged. We conclude that nadolol 80 mg once daily lowers ambulatory blood pressure in patients with mild to moderate hypertension without impairment of renal blood flow, indicating a redistribution of cardiac output to the kidneys. The mechanism of the renal vasodilator effect of nadolol remains to be determined.

The present study was designed to characterize the neuronal dopamine receptors involved in the inhibitory effect of apomorphine on neurogenic vasoconstriction in the isolated autoperfused hindquarters, renal and superior mesenteric vascular beds of the rat. In the three vascular beds, the inhibitory effect of apomorphine on neurogenic vasoconstriction was antagonized by the selective DA2-receptor antagonist domperidone, but not by the selective DA1-receptor antagonist SCH 23390. Local administration of these antagonists had no effect on the perfusion pressure per se or on the pressure response to electrical stimulation of the sympathetic innervation. These results show that the neuronal dopamine receptors present in the rat hindquarters, renal and superior mesenteric vascular beds can be classified as DA2-receptors.

The effect of fenoldopam, a selective DA1-agonist, on the plasma aldosterone response to metoclopramide was studied in six hypertensive patients included in a multicentre double-blind placebo controlled cross-over study of the antihypertensive effects of fenoldopam. Fenoldopam significantly increased baseline plasma renin activity (PRA); baseline plasma aldosterone levels rose slightly. Baseline PRL and the PRL response to metoclopramide were not altered by fenoldopam. After metoclopramide, a significant increase of plasma aldosterone was observed during treatment with fenoldopam, as well as in the placebo-period. The peak values were not significantly different and occurred at 15 min during both treatment periods. These results indicate that fenoldopam does not reduce metoclopramide-induced aldosterone secretion and therefore suggest that the adrenal dopamine receptor is not identical to the vascular DA1 receptor.