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Increased intima-media thickness of the common carotid artery predicts increased risk of myocardial infarction and stroke. Preliminary evidence suggests that a decrease in blood pressure (BP) is associated with diminished wall thickness. It is not known if all classes of anti-hypertensive agents have similar protective effects. In this double-blind parallel-group clinical trial, 69 previously untreated patients with hypertension were allocated randomly to 1 year of treatment with either amlodipine (5-10mg daily) or lisinopril (5-20mg daily). Doxazosin and bendrofluazide were added if required to achieve BP control. After 12 months of treatment, clinic BP, ambulatory BP and cardiac mass were reduced similarly by the two treatment regimens. Common carotid artery intima-media thickness decreased by 0.048mm (95% confidence intervals -0.066, -0.031mm) in the amlodipine-treated group, but decreased by only 0.027 mm (-0.046, -0.007mm) in the lisinopril-treated group (P < 0.05 for difference between treatments). Common carotid artery lumen diameter declined significantly only in patients treated with lisinopril [amlodipine, -0.02mm (-0.14, 0.10mm); lisinopril, -0.21mm (-0.32, -0.11mm); P < 0.02], while intima-media area declined similarly in the two treatment groups [amlodipine -1.32mm2 (-1.91, -0.74mm2), lisinopril -1.26mm2 (-1.80, -0.72mm2); not significant]. The results confirm that a decrease in BP causes regression of structural changes in the carotid artery in hypertensive patients. The nature of the structural regression differed markedly between the two treatment regimens, in spite of similar decreases in BP. The calcium channel blocker induced greater regression of common carotid artery intima-media thickness than the angiotensin-converting enzyme inhibitor. However, carotid artery wall mass, as indicated by intima-media area, was reduced to a similar extent by the two treatments. It remains to be established whether such differences confer a prognostic advantage.

1. Plasma noradrenaline concentration and plasma renin activity were measured in a control, British, urban population (n = 115) in which blacks were matched for age and sex with whites. 2. Similar measurements were made in subjects with essential hypertension (77 white and 23 black), and 48 healthy normotensive white civil servants. 3. In controls blood pressure was significantly higher in blacks; it correlated with age in both races and with pulse rate in blacks. There were no significant racial differences in plasma noradrenaline which was positively correlated with age in both blacks and whites. Mean plasma renin activity was 55% lower in blacks, and this difference was not related to urinary sodium excretion. 4. In hypertensive subjects plasma noradrenaline positively correlated with age in blacks. This relationship was not found in whites in whom 20% of young hypertensive subjects (<45 years) had significantly raised plasma noradrenaline. Plasma renin activity was again significantly lower in blacks. In white hypertensives plasma noradrenaline and renin activity were significantly correlated. 5. There may be racial differences in the pathogenesis of essential hypertension.

1. The effects of coitus on heart rate, blood pressure and plasma concentration of noradrenaline were studied in six male rabbits. 2. During coitus, heart rate rose from 228 ± 6 to 324 ± 8 beats/min (mean ± sem; n = 24). Mean blood pressure rose from 87 ± 3 to 165 ± 4 mmHg, and plasma concentration of noradrenaline from 2.07 ± 0.21 to 5.02 ± 0.26 nmol/l. The maximum heart rate did not occur until after the peak in blood pressure. 3. Propranolol had no effect on the power expended during coitus, but there was a dose dependent fall in the changes in heart rate, blood pressure and plasma concentration of noradrenaline.

1. The effect of a α-human atrial natriuretic peptide (1–28) (ANP) on human vasculature was investigated in vivo and in vitro. Possible involvement of vascular dopamine receptors and the renin-angiotensin system in the response to ANP was also studied in vivo. 2. Forearm blood blow was measured by venous occlusion plethysmography. Isolated human blood vessels were studied using conventional organ bath techniques. 3. ANP (0.1–1 μg/min, intra-arterially) produced a dose-dependent increase in forearm blood flow, corresponding to a 163% increase in net forearm blood flow in the study arm. This action of ANP was not antagonized by (R)-sulpiride (100 μg/min, intra-arterially), a selective vascular dopamine receptor antagonist, or 50 mg of oral captopril, an inhibitor of angiotensin-converting enzyme. 4. ANP (1 nmol/l–1 μmol/l) produced concentration-dependent relaxation of isolated human arteries, including brachial artery, but was without effect on isolated human saphenous vein. 5. ANP produces vasodilatation in vivo and relaxes isolated human arterial smooth muscle. This action of ANP may contribute to its reported hypotensive effects in vivo.

1. The role of the endothelium in mediating relaxation to acetylcholine, the calcium ionophore A23187, vasoactive intestinal peptide and peptide histidine methionine was studied using isolated human blood vessels. 2. Segments of renal, colic, pulmonary, uterine, transverse cervical, brachial, coronary and coeliac branch arteries, and saphenous veins, were obtained from surgical resection material for use in tissue bath studies. 3. Acetylcholine or A23187 produced endothelium-dependent relaxation in isolated vessels from all vascular beds studied. Coronary arteries, however, differed in their response to acetylcholine which produced predominantly a contractile response, either alone or after initial relaxation. 4. Vasoactive intestinal peptide and peptide histidine methionine produced endothelium-dependent relaxation in coeliac branch arteries. However, these peptides relaxed isolated pulmonary arteries independently of endothelium. 5. Endothelium-dependent relaxation in response to acetylcholine and A23187 was antagonized by nordihydroguaretic acid, a lipoxygenase inhibitor, and methylene blue and haemoglobin, inhibitors of soluble guanylate cyclase. In these respects the endothelium-dependent responses of human arteries to acetylcholine and A23187 resemble those described in other species.

1. The number of β-adrenoceptors and their affinity for the radioligand 125I-labelled cyanopindolol (125I-CYP) were measured in crude membrane preparations of left ventricle, spleen and lung from Wistar rats exposed to 28 days continuous hypoxia. 2. β-Adrenoceptor density in the left ventricle was not significantly altered after exposure to chronic hypoxia (binding site maxima, Bmax: normoxic control 36 sem 5, hypoxic 24.8 sem 2 fmol/mg of protein). There was no change in β-adrenoceptor number in the spleen in response to chronic hypoxia (Bmax: normoxic control 76 sem 19 fmol/mg of protein, hypoxic 80 sem 15 fmol/mg of protein). 3. Chronic hypoxia resulted in a significant increase in β-adrenoceptor number in lung tissue (binding site maxima, Bmax.: normoxic control 406 (sem 31) fmol/mg of protein; hypoxic 535 (sem 30) fmol/mg of protein, P < 0.01 without change in the dissociation constant (KD) of the radioligand. 4. β-Adrenoceptor subtypes in lung homogenates were studied by establishing displacement curves for 125I-CYP by ICI 118551 (a selective β2-antagonist). A significant difference was seen in the proportion of β1-/β2-adrenoceptor subtypes after hypoxia (normoxic control 66 sem 2.5%, hypoxic 79 sem 2.4% β2-adrenoceptors, P < 0.01). 5. α1-Adrenoceptor number in lung membranes was measured with 125I-labelled 2-[β-(4-hydroxyphenyl)ethylaminomethyl]tetralone (125I-HEAT). No difference was seen in the number of α1-receptors in normoxia and in chronic hypoxia [Bmax.: normoxic control 48 (sem 3), hypoxic 48 (sem 5) fmol/mg of protein]. 6. Treatment with salbutamol (2.5 mg/kg twice daily subcutaneously) did not reduce the number of β-adrenceptors in lung either during normoxia or in hypoxia. In spleen β-adrenoceptor number was decreased by 80% after chronic salbutamol treatment of rats in normoxia [Bmax.: normoxic control 76 (sem 19) fmol/mg of protein, treated 14 (sem 7) fmol/mg of protein, P < 0.01]. After treatment during hypoxia, however, there was no significant reduction in β-adrenoceptor number in spleen [Bmax.: hypoxic control 80 (sem 15) fmol/mg of protein, treated 77 (sem 13) fmol/mg of protein]. 7. These data suggest that there is a tissue specific modulation in β-adrenoceptor numbers in response to chronic hypoxia and that their capacity for down-regulation is reduced.

1. The effects of compounds with a2-agonist and a2-antagonist properties on human forearm blood flow and on isolated human arterial segments have been studied. 2. The findings from these studies in vivo and in vitro did not provide evidence in support of the hypothesis that postsynaptic a2-receptors mediate smooth muscle contraction in the tissues under investigation. 3. The constriction of the forearm vascular bed in response to low intra-arterial doses of idazoxan (RX 781094), an a2-antagonist, provides evidence for a physiological role for a presynaptic a2 autoregulatory mechanism. 4. The variability of the forearm vascular responses to higher doses of idazoxan highlights the pitfalls that may have misled previous authors in their interpretation of the results of similar studies. A U-shaped dose-response curve to compounds with mixed a2-and a1-antagonist properties may be constructed, which emphasizes the importance of the dose-dependent selectivity of these antagonists at a2- and a1-receptors. 5. The effect of idazoxan on the responses of arterial segments in vitro to exogenous catecholamines was dependent on the integrity of the endothelium, and provides evidence that a2-receptors may mediate release of the endothelium-derived relaxing factor.

1. The cardiovascular and hormonal effects of intravenous saralasin (0.5, 1 and 5 μg min−1 kg−1) were assessed in nine tetraplegic patients (with complete cervical spinal cord transaction above the sympathetic outflow) and in six normal subjects. 2. In the tetraplegic patients, saralasin caused an immediate transient pressor response which was not dose-dependent and substantially greater than the pressor response in normal subjects. The pressor response in the tetraplegic patients was not accompanied by a rise in levels of plasma noradrenaline. 3. In the tetraplegic patients, after α-adrenoceptor blockade with thymoxamine (1 mg kg−1 h−1), twice the dose of intravenous noradrenaline was needed to induce the same pressor response. The pressor response to saralasin (5 μg kg−1 min−1), however, was unaffected by thymoxamine. 4. Saralasin caused minimal changes in levels of plasma renin activity and plasma aldosterone in both groups. There was no relationship between basal plasma renin activity and the pressor response in either group. 5. We therefore conclude that the immediate transient pressor response to saralasin in man is not due to central sympathetic stimulation, is unlikely to be due to peripheral sympathetic activation and is probably the result of intrinsic angiotensin II-like myotropism.

1. Plasma noradrenaline concentrations and platelet a-receptor properties were measured in 14 normal subjects, five phaeochromocytoma patients and nine patients with multiple system atrophy and sympathetic nervous system degeneration (MSA). 2. Plasma noradrenaline concentrations in phaeochromocytoma were 10- to 20-times greater than those of normal subjects and one-fifth to one-half of normal in MSA patients. 3. Platelet a-receptor numbers were increased in MSA and decreased in phaeochromocytoma compared with normal subjects. There was no change in platelet a-receptor affinity in either group. 4. The inverse relationship between a-receptor numbers and plasma noradrenaline concentrations may reflect regulation of a-receptor number by endogenous adrenergic agonist concentrations in man.

1. A single oral dose of clonidine hydrochloride (300 µg) lowered systolic blood pressure by 20 ± 2 mmHg and diastolic blood pressure by 15 ± 2 mmHg in seven healthy normotensive subjects. 2. Resting supine plasma noradrenaline concentration fell from 2·42 ± 0·47 nmol/l before dosing to a minimum of 0·59 ± 0·18 nmol/l at 6 h. The value subsequently rose and was not significantly different from that before the dose at 12 h. There was a significant reduction in urinary free catecholamine excretion in the first 12 h after dosing. 3. Resting supine plasma renin activity before dosing was 0·95 ± 0·16 pmol of angiotensin I h-1 ml-1 of plasma and rose significantly after clonidine to 3·50 ± 0·39 pmol of angiotensin I h-1 ml-1 of plasma at 6 h. By 12 h plasma renin activity had returned to control values. 4. When the same subjects were studied on a control, drug-free, day under the same conditions, there was no significant change in blood pressure or plasma noradrenaline. Although plasma renin activity rose during this control day, it was significantly lower than after clonidine. 5. In normotensive subjects single doses of clonidine lower blood pressure and are associated with a reduction of sympathetic nervous activity. Delayed elevation of plasma renin activity may be secondary to the fall in blood pressure. There is no evidence for an overshoot of sympathetic activity after a single dose of clonidine.

1. Small arteries were isolated from either rat mesentery or human subcutaneous fat, and mounted in a myograph for the measurement of isometric force. 2. Superoxide dismutase, either in the presence or absence of catalase, relaxed noradrenaline-induced tone. This effect was abolished by removal of the endothelium or incubation with an inhibitor of NO synthase, N-ω-nitro-L-arginine methyl ester. Catalase alone had a negligible effect on noradrenaline-induced tone. 3. Captopril, an angiotensin-converting enzyme inhibitor and putative free-radical scavenger, did not relax pre-contracted isolated vessels. N-Acetylcysteine caused an endothelium-independent relaxation of rat vessels. Similar effects were observed in human vessels. 4. Acetylcholine induced a concentration-dependent relaxation of isolated resistance arteries, which was inhibited by removal of the endothelium or N-ω-nitro-L-arginine methyl ester, but unaffected by indomethacin. Preincubation with captopril, N-acetylcysteine or catalase alone did not alter the acetylcholine concentration-response relationship, but superoxide dismutase in combination with catalase enhanced responses to acetylcholine, causing a six-fold increase in potency. 5. Superoxide dismutase causes endothelium-dependent relaxation of resistance arteries and potentiates responses to acetylcholine. This action is probably due to the ability of the enzyme to scavenge superoxide anions which inhibit endothelium-dependent relaxation. 6. N-Acetylcysteine causes an endothelium-independent relaxation of resistance arteries which is probably unrelated to the putative ability of this compound to scavenge superoxide radicals and may reflect a direct action on vascular smooth muscle.