Clinical science and molecular medicine. Supplement最新文献

1. The biotransformation of arachidonic acid and prostacyclin in the circulation was studied in anaesthetized dogs, using the blood-bathed organ technique. 2. In passage through the lungs, arachidonate (50-800 microgram kg-1 min-1) was transformed into prostacyclin. No thromboxane A2 or prostaglandin E2 could be detected in arterial blood. 3. In dogs treated with indomethacin (5 mg/kg), intravenous infusions of arachidonate had no cardiovascular effects and no prostacyclin was produced. Therefore, the vasodilator effects of arachidonate in vivo may be attributable to prostacyclin formation. 4. Prostacyclin, unlike prostaglandin E2, is not inactivated by passage across the lungs, and only about 50% disappears in one passage through peripheral vascular beds. 5. Thus prostacyclin released from the lungs could function as a circulating vasodilator and contribute to the regulation of blood vessel tone and blood pressure.

1. Hypertension was induced in rats by renal artery clip with the contralateral kidney removed (Goldblatt I) or left intact (Goldblatt II). 2. Plasma noradrenaline was increased 62% in the Goldblatt I animals after 3 weeks. 3. Hypothalamic tyrosine hydroxylase and dopamine beta-hydroxylase activities, and the concentration of noradrenaline were increased in the Goldblatt I animals after 3 weeks. 4. Enhanced hypothalamic noradrenaline synthesis may be a pathogenic factor in Goldblatt I renovascular hypertension.

1. Angiotensin I-generating activity of rat brain extract was separated into two components by affinity chromatography on a casein-Sepharose gel column. 2. The component without affinity to the gel was identified as true renin on the basis of its sensitivity to anti-renin antibody and the lack of protease activity. 3. The second renin-like component with affinity to the gel was a protease insensitive to the anti-renin antibody. Its renin-like activity examined with sheep substrate was pronounced compared with the rate of angiotensin I generation from the rat substrate. 4. It was concluded that rat brain contains true renin, which can be detected by the use of rat substrate but can be masked when examined with sheep substrate.

1. Serial venous blood samples were obtained from 45 patients with acute myocardial infarction. Ten of these patients were receiving beta-adreno-receptor-blocking drugs at the time of onset of chest pain and continued on these drugs during their stay in the coronary care unit. The activities of creatine kinase and its MB-isoenzyme (CK-MB) were assayed in the plasma. A lysosomal enzyme, beta-N-acetylglucosaminidase, was also assayed. 2. In the 35 untreated patients it was found that creatine kinase activity was maximal at a mean time of 21.3 +/- 1.3 h after the onset of chest pain, whereas in the patients receiving beta-adrenoreceptor-blocking drugs peak activity of the enzyme occurred at 24.4 +/- 0.7 h. 3. Peak CK-MB acitivity was also delayed from 18.1 +/- 1.6 h in the control group to 22.4 +/- 1.2 h in the treated patients. 4. The lysosomal enzyme showed a similar pattern of changes to that of CK-MB. Maximum activity in plasma occurred at 18.0 +/- 1.0 h after the onset of chest pain in the control group of patients. In the treated patients peak lysosomal enzyme activity was not found until 24.2 +/- 1.2 h. 5. These alterations in the time-course of plasma enzyme changes after acute myocardial infarction are consistent with the suggestion that beta-receptor antagonists may delay tissue damage during myocardial ischaemia.

1. In subjects with normal renal function there was a strong positive correlation between serum concentrations of 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol, as measured by competitive protein-binding assay. 2. The 24,25-dihydroxycholecalciferol concentration was about 7% of the prevailing 25-hydroxycholecalciferol concentration. 3. In contrast, sera from anephric patients contained very low or undetectable amounts of 24,25-dihydroxycholecalciferol even after the serum 25-hydroxycholecalciferol concentrations in these patients had been elevated by oral administration of 25-hydroxycholecalciferol. 4. In a further group of anephric patients, all having normal serum 25-hydroxycholecalciferol concentrations, no radioactively labelled 24,25-dihydroxycholecalciferol was formed from an injected pulse dose of [3H,14C]cholecalciferol. 5. These results indicate that in man the kidney is the major site of 24-hydroxylation of 25-hydroxycholecalciferol.

1. An inverse relationship was found between plasma noradrenaline and reactivity to exogenous noradrenaline in normotensive subjects. 2. The relationship between plasma noradrenaline and reactivity was distrubed in age-matched patients with essential hypertension. 3. A multiple-regression analysis showed a highly significant correlation between adrenergic activity and reactivity to noradrenaline and the mean arterial blood pressure level (r = 0.91). The results suggest that adrenergic activity and pressor response to noradrenaline combined are important determinants of arterial blood pressure. 4. An inverse relationship could also be demonstrated between plasma renin activity and reactivity to exogenous angiotensin II. No difference was observed between normotensive and hypertensive subjects.

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 (less than 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 effect of diuretic therapy on serum lipids and lipoprotein fractions was evaluated in 16 normal or labile hypertensive subjects who received in cross-over fashion chlorthalidone, frusemide or mefruside, each for 4 weeks (group A); and in 13 patients with essential hypertension treated with chlorthalidone for 6 weeks (group B). 2. All three diuretics significantly increased the ratio between serum beta- and alpha-lipoprotein fractions. This was due to an increase of the serum beta-lipoprotein fraction while the alpha-lipoprotein fraction was not changed significantly (group A) or decreased (group B). Serum cholesterol or triglycerides tended to be increased, but mean changes were often not significant. 3. The observed alterations in serum lipoproteins are consistent with the possibility of an increased risk for coronary heart disease which could offset partly the beneficial effects of a lowered blood pressure in diuretic-treated patients with hypertension.

1. A questionnaire, modified from Bulpitt & Dollery (1973), inquired about 20 symptoms commonly associated with hypertension or its drug therapy in 1017 subjects (age 30--69 years). Groups consisted of (a) active therapy, (b) placebo, (c) no tablets, and (d) a non-study control group. The response rate was 96% in the first three groups and 92% in group (d). 2. The subjects in groups (a), (b) and (c) constituted part of a placebo-controlled, patient-blind intervention study in the treatment of mild hypertension (The Australian National Blood Pressure Study). 3. After age/sex adjustment of the data, only sleepiness and self-assessed depression were found to be more common in the actively treated group. Impotence, failure of ejaculation and nocturia were age-related symptoms. Generally, complaint rate was higher in females. 4. The knowledge of a mild hypertensive condition or its modern drug therapy lead to very few symptoms in a non-hospital population who already have a fairly high 'complaint level'.

1. Salt depletion was produced in five dogs by a low salt diet and daily administration of frusemide for 5 days; a control group of five dogs was placed on the same diet, to which 2.5 g of sodium chloride was added. 2. Saralasin infusion (0.5 microgram min-1 kg-1) reduced mean aortic blood pressure and total peripheral vascular resistance and increased cardiac output in salt-depleted dogs, but did not affect the heart rate and left ventricular dP/dt. 3. Saralasin infusion increased mean aortic blood pressure slightly in normal dogs; other systemic haemodynamic parameters did not change significantly. 4. Saralasin decreased hepatic arterial flow in both normal and salt-depleted dogs, but increased blood flow to left ventricle and kidneys only in salt-depleted dogs. 5. These results suggest that saralasin exerts a partial agonist effect in normal dogs to increase arterial blood pressure, but causes a depressor response during salt depletion because it reverses the vasoconstrictor effect of angiotensin II, particularly on the renal and coronary circulations.