Decreased central dopaminergic activity in essential hypertension.

Baseline serum prolactin (PRL) was found to be similar in 35 men with untreated essential hypertension (149 +/- 2/98 +/- 1 mmHg; means +/- s.e.) and 44 healthy normotensive men (126 +/- 1/80 +/- 1 mmHg), all 40 years old. A correlation between baseline PRL and aldosterone was found in the normotensive (r = 0.534, P less than 0.001), but not in the hypertensive group (r = -0.011, NS). Ten subjects from each group received intravenous metoclopramide, a competitive dopamine antagonist, while another 12 normotensive subjects were given saline only, and the effect on PRL, vasopressin (AVP) and catecholamines was followed. An exaggerated PRL response to metoclopramide was observed in the hypertensive group compared with the normotensive (P less than 0.05), and the mean normotensive peak value never exceeded the hypertensive. Plasma noradrenaline increased significantly compared with baseline (P less than 0.05) and the control group (P less than 0.001), concomitant with increased heart rate (P less than 0.05), after the administration of metoclopramide both in the hypertensive and normotensive group. After intravenous injection of metoclopramide, forearm blood flow increased significantly by 50% in the hypertensive (P less than 0.001), and 80% in the normotensive group (P less than 0.001) compared with the control group. Mean blood pressure remained unchanged as did plasma AVP, dopamine and adrenaline. The present study indicates an altered central dopaminergic activity in essential hypertension. Even at rest, endogenous dopamine exerts a modulating effect on noradrenaline release in both hypertensive and normotensive men.

Plasma adrenaline and noradrenaline during orthostasis in man: the importance of arterial sampling.

Plasma adrenaline and noradrenaline were measured in arterial blood and in forearm venous blood during supine rest and after 30 min standing in normotensive, healthy 50-year-old men (n = 16). After 30 min standing, venous noradrenaline had increased from 1.61 +/- 0.11 to 4.22 +/- 0.30 nmol/l and arterial from 1.43 +/- 0.06 to 2.93 +/- 0.15 nmol/l. Orthostasis induced a seven-fold increment in the forearm arterial-venous difference of noradrenaline from -0.18 +/- 0.08 to -1.29 +/- 0.25 nmol/l (p less than 0.001). Orthostasis more than doubled the forearm arterial-venous difference of adrenaline from 0.15 +/- 0.03 to 0.31 +/- 0.05 nmol/l (p less than 0.001) since arterial adrenaline increased from 0.31 +/- 0.03 to 0.53 +/- 0.05 nmol/l and venous from 0.16 +/- 0.02 to 0.22 +/- 0.02 nmol/l. Arterial adrenaline correlated significantly with venous in the supine (r = 0.64, p less than 0.01) but not in the standing position (r = 0.34, NS). The results indicate that arterial concentrations of adrenaline are a much better indicator of sympatho-adrenal activity during orthostasis than peripheral venous concentrations. For noradrenaline, measurements of arterial concentrations during the orthostatic manoeuvre seem to provide information about the total noradrenergic sympathetic reactivity, while the corresponding measurements in peripheral venous blood represent the forearm locally.

Enhanced platelet release reaction related to arterial plasma adrenaline and blood pressure in pre-eclampsia.

The platelet release product beta-thromboglobulin (BTG) in venous plasma, and arterial and venous catecholamines were measured in 13 severe pre-eclamptic and 13 normotensive pregnant women. In the pre-eclamptic group, BTG was significantly higher and the platelet count significantly lower than in the normotensive pregnant group. In the pre-eclamptic group, arterial concentrations were significantly higher for adrenaline, noradrenaline and dopamine, whereas in venous plasma only adrenaline and dopamine were higher. Significant positive correlations appeared in the pre-eclamptic patients between venous BTG and arterial adrenaline (r = 0.82), arterial noradrenaline (r = 0.76) and venous adrenaline (r = 0.55). In the pre-eclamptic group, BTG also highly correlated with systolic (r = 0.84) and diastolic blood pressure (r = 0.77) and heart rate (r = 0.67). These findings indicate that sympathetic nervous tone, as measured by arterial and venous plasma catecholamines, is a good predictor of in-vivo blood platelet activation. In pre-eclampsia, increased sympathetic tone may play a key role in platelet activation and consumption and thus in the activation of the coagulation system.

Increased plasma vasopressin in low renin essential hypertension.

Baseline plasma vasopressin concentrations were measured in 48 men (all 50 years old) with decreased plasma renin concentration and untreated, sustained essential hypertension and in 29 healthy normotensive men. Mean hypertensive plasma vasopressin concentration was more than twice as high as the corresponding normotensive level (15.7 +/- 2.2 [SE] vs 7.5 +/- 1.0 pg/ml; p less than 0.001). Plasma renin concentration in the hypertensive group was reduced compared with that in the normotensive group (0.28 +/- 0.04 vs 0.46 +/- 0.06 Goldblatt units X 10(-4)/ml). These differences appeared despite virtually identical serum osmolality, creatinine clearance, and urinary sodium excretion in the two groups. In the first 38 hypertensive subjects, arterial plasma epinephrine concentrations were significantly increased over those of the first 28 control subjects (99 +/- 12 vs 68 +/- 6 pg/ml; p less than 0.025). In contrast to those with low renin essential hypertension, 35 men with normal renin essential hypertension (all 40 years old) had normal plasma vasopressin levels that were not significantly different from those in a comparable normotensive control group (3.7 +/- 0.8 vs 3.5 +/- 0.4 pg/ml). Arterial epinephrine concentrations were not significantly different between normal renin subjects and the control group. After 6 weeks of treatment with the nonselective beta-adrenergic receptor blocker oxprenolol in 11 subjects with low renin hypertension, blood pressure was reduced and the plasma vasopressin concentration fell from 27.6 +/- 6.4 to 13.5 +/- 4.2 pg/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of serum, alpha-1 acid glycoprotein, lipoproteins and albumin on human mononuclear leucocyte beta-adrenoceptors.

The effects of serum, alpha-1 acid glycoprotein (AAG), serum lipoproteins (SLP) and human serum albumin (HSA) on 3H-(-)-dihydroalprenolol (3H-(-)-DHA) binding and (-)-isoproterenol ((-)-IPR) induced cyclic AMP (cAMP) elevation in human peripheral blood mononuclear leucocytes (MNL) were investigated. The saturable binding of 3H-(-)-DHA was decomposed into two classes of binding sites with maximum binding capacity of approximately 1400 and 30000 sites/cell and with dissociation constants (Kd) of approximately 0.7 and 65 nM. Stimulation of the MNL beta-adrenoceptors by (-)-IPR caused a concentration dependent cAMP accumulation (EC50 approximately 0.2 microM) with maximum level approximately 250% above basal. For all single leucocyte preparations, 30-35 min. exposure to serum, AAG and SLP increased the number of beta-adrenoceptors with 100-200% and the maximal responsiveness to (-)-IPR with 30-90%. The presence of proteins did not change the Kd or the EC50. (-)-Alprenolol inhibited concentration dependently the serum induced increment in (-)-IPR-responsiveness. Serum, AAG and SLP did also increase the number of low affinity binding sites with 25-40% without effect on the Kd. HSA had no consistent effect on beta-adrenergic binding or stimulation. The present study shows that serum, AAG and SLP influence the number and function of MNL beta-adrenoceptors in vitro.

Central dopaminergic control of prolactin in essential hypertension.

An exaggerated, early prolactin response (p less than 0.01) was observed in ten patients with untreated essential hypertension (148 +/- 4/97 +/- 1 mmHg, means +/- SE) compared with ten healthy normotensive men of the same age (124 +/- 3/78 +/- 2 mmHg) after administration of metoclopramide, a competitive dopamine antagonist. The normotensive peak value of prolactin never exceeded that of the hypertensive (p less than 0.05). Since prolactin is considered an indicator of central dopaminergic activity, these findings suggest an altered central dopaminergic activity in mild essential hypertension.

Serum phosphate and sympathetic tone in mild essential hypertension.

Forty-year old, normocalcaemic men with mild essential hypertension (n = 35) had decreased serum phosphate (p less than 0.001) concomitant with elevated plasma adrenaline (p less than 0.03) and heart rate (p less than 0.001). All had unchanged serum immunoreactive parathyroid hormone concentrations compared to age-matched normotensive control men (n = 44). Serum phosphate levels correlated negatively with plasma adrenaline (p less than 0.05), plasma noradrenaline (p less than 0.05), mean blood pressure (p less than 0.001) and heart rate (p less than 0.05). Serum phosphate was significantly lowered by infusion of small amounts of adrenaline at all four infusion rates in a hypertensive group (n = 12) while a similar effect was obtained only at the two highest infusion rates in a normotensive group (n = 10). No change in serum calcium was observed in either group. Thus, hypophosphataemia appears to be inversely related to sympathetic tone in essential hypertension.

Blood platelet release correlates with serum lipids in 50 year old men with essential hypertension.

50 year old men with moderate, essential hypertension (n = 39) were compared to normotensive males of similar age (n = 31). The hypertensive men were heavier (10 kg in average, p less than 0.01), and had a higher pulse rate (5 beats per minute (p less than 0.05). Plasma beta-thromboglobulin, a marker of platelet release reaction, was 49% higher in the hypertensive group (p less than 0.01). Total cholesterol, LDL + VLDL cholesterol and serum triglycerides were not significantly different between the groups. In the hypertensive group, plasma beta-thromboglobulin concentration correlated significantly with total cholesterol (r = 0.47, p less than 0.01) as well as with LDL + VLDL cholesterol (r = 0.50, p less than 0.01). In the normotensive group no such correlation was found. The results suggest activation of platelets in hypertension, and suggest that in hypertension, even a normal cholesterol concentration may influence platelet function.

Platelet volume, platelet release reaction and platelet response to infused adrenaline are increased in essential hypertension.

Hypertensive men aged 42 (n = 35) were compared to normotensive men of similar age (n = 44). Platelet numbers were similar in the two groups, but hypertensive men had larger venous platelets than the normotensive (7.46 versus 7.12 femtoliter, p = 0.01). Plasma concentration of beta-thromboglobulin (BTG), a marker of platelet release reaction, was increased in arterial blood in hypertension (40 versus 21 micrograms/l, p = 0.02). The normotensive subjects had markedly higher BTG concentration in venous compared to arterial blood (p less than 0.01), but this arterio-venous difference was not present in the hypertensive group. Twelve normotensive subjects received infused saline, which did not induce changes in platelet variables. Adrenaline was infused to 13 hypertensive and 12 normotensive subjects, with dose gradually increasing to 0.04 microgram/kg/min. Platelet count increased in both groups, but significantly more in the hypertensive group. Platelet volume and BTG both increased markedly in the hypertensive group, but not in the normotensive men. Thus, young men with hypertension have increased platelet activity and increased sensitivity to exogenous adrenaline.

Hormonal responses to treatment of high blood pressure with low-salt diet alone and combined with added potassium.

One week strict sodium depletion in essential hypertensive men (n = 17) decreased blood pressure and body weight. Plasma renin concentration increased four-fold (p less than 0.001), plasma noradrenaline with 38% (p less than 0.001), plasma dopamine with 58% while plasma adrenaline remained unchanged. The urinary excretion of vasopressin was reduced with 50% (p less than 0.001). Extra potassium induced only small changes when already sodium depleted. Thus, vasopressin was the only pressor hormone which varied directly with sodium intake, blood pressure and body weight during sodium depletion.

Increased arterial adrenaline is highly correlated to blood pressure and in vivo platelet function in pre-eclampsia.

Compared with normotensive pregnant women (n = 13), patients with severe pre-eclampsia (n = 13) had increased arterial plasma adrenaline (P < 0.001), peripheral venous adrenaline (P < 0.01), arterio-venous differences of adrenaline (P < 0.001) and venous concentration of the platelet release product beta-thromboglobulin (P < 0.001). In the pre-eclamptic group, arterial adrenaline correlated with mean blood pressure (r = 0.90, P < 0.001), heart rate (r = 0.78, P < 0.01) and beta-thromboglobulin (r = 0.82, P < 0.001), while in the normotensives adrenaline correlated only with beta-thromboglobulin (r = 0.76, P < 0.01). According to these results, sympathetic adrenal tone is increased in pre-eclampsia and may play a role in the pathogenesis of high blood pressure and platelet activation in this disease.

Dietary sodium intake increases vasopressin secretion in man.

Plasma vasopressin concentration and urinary vasopressin excretion were measured in a control situation, during sodium depletion and on days 1, 2, and 7 during high sodium intake in twelve 23-26-year-old men on a free-water intake. Urinary vasopressin excretion decreased from 6.7 +/- 1.0 ng/hr (control) to 3.9 +/- 0.3 ng/hr (p less than 0.01) when sodium excretion decreased from 188 +/ 18 to 16 +/- 2 mmol/24 hr. During the first day of high sodium intake, the urinary vasopressin excretion increased to 10.0 +/- 1.2 ng/hr (p less than 0.01) compared with control and remained high throughout the sodium repletion. Through all collection periods at low, normal, and high sodium intake, vasopressin excretion increased concomitantly with serum sodium concentration and osmolality. After low sodium intake for 7 days, the serum vasopressin concentration averaged 2.7 +/- 0.6 ng/l, and this level was maintained throughout the sodium repletion period. These results are compatible with a stimulatory effect of dietary sodium intake on pituitary vasopressin secretion in man. Dietary sodium may stimulate vasopressin secretion through extracellular osmolality or even by a direct effect of extracellular sodium on periventricular receptors. Plasma renin concentrations or sympathetic nervous activity offered no further explanations. Urinary vasopressin excretion provides more useful information than do plasma concentrations, as the latter can fluctuate rapidly.

Evidence of age-related variation in plasma vasopressin of normotensive men.

The influence of age on plasma arginine vasopressin was examined in three groups of healthy men, 25 +/- 1 (n = 12), 40 (n = 23) and 50 years of age (n = 13), respectively. The three groups were comparable in body height, weight, blood pressure, heart rate, serum and urine osmolality, electrolytes and endogenous creatinine clearance. Compared to the 25-year olds, the 50-year old men had more than three times higher basal plasma vasopressin (7.8 +/- 1.4 vs. 2.5 +/- 0.6 ng/l, p less than 0.01), only one-third the plasma renin concentration (0.36 +/- 0.05 vs. 1.10 +/- 0.33 G.U. X 10(-4)/ml, p less than 0.01) and a significantly higher plasma noradrenaline (267 +/- 21 vs. 199 +/- 19 ng/l, p less than 0.05) while plasma adrenaline remained essentially unchanged. The 40-year olds had intermediate plasma vasopressin concentrations (4.2 +/- 0.6 ng/l). Thus, age is a variable with a substantial effect on plasma concentrations of vasopressin in addition to the well-known effect on renin and noradrenaline. Age must be taken into account in further clinical studies on vasopressin.

Plasma vasopressin in hereditary cranial diabetes insipidus.

A family comprising 46 members of 4 generations is described; 21 members suffered from incomplete diabetes insipidus (DI) of central origin. The pedigree showed a dominantly transmitted condition. The onset is gradual and starts in early infancy. The clinical symptoms are highly variable and decline in the sixth decade. Plasma vasopressin (AVP) during water deprivation was significantly lower in the DI group than in the controls (4.2 +/- 0.5 vs. 10.6 +/- 1.7 ng/l) (p less than 0.01), the difference being more pronounced in the high osmolality range (4.8 +/- 0.7 vs. 14.4 +/- 3.1 ng/l) (p less than 0.01). Urine osmolality was lower (241 +/- 36 vs. 928 +/- 46 mOsm/kg H2O) (p less than 0.01) despite higher serum osmolality during water deprivation, rendering the ratio between urine and serum osmolality less than unity compared with greater than 3:1 in the control group (p less than 0.001). In two affected females, addition of a non-osmotic stimulus caused no increase in plasma AVP. The findings are consistent with a partial defect in the production or release of AVP and not with a dysfunction of the intracranial osmoreceptors. The variable features of incomplete DI indicate that to define the condition by excessive urinary output alone is insufficient. The ratio between urine and serum osmolalities after an appropriate osmotic stimulus together with plasma AVP measurements may be necessary to confirm the diagnosis.

Dietary sodium intake and vasopressin excretion in man.

The present study was undertaken to examine the possible relationship between dietary sodium intake and arginine vasopressin (AVP). In 12 normotensive men (aged 23-26 years) urinary AVP excretion decreased from 6.7 +/- 1.0 to 3.9 +/- 0.3 ng/h (P less than 0.01) when sodium excretion by dietary intervention for one week was reduced from 188 +/- 18 to 16 +/- 2 mmol/24 h. At a high sodium intake (300 mmol/day), AVP excretion increased to 10.0 +/- 1.2 ng/h during the first day (P less than 0.01) and remained high throughout one week of sodium load. These results are compatible with a major physiological role of sodium in AVP secretion in man. A sodium-AVP relationship may play a role in the pathogenesis of essential hypertension since recent reports suggest elevated plasma AVP in essential hypertensive states.

Arteriovenous difference of plasma vasopressin in normal man and effect of posture.

In 13 normotensive 50-year-old men arterial plasma vasopressin (11.3 +/- 2.1 ng/l, mean +/- SE) was significantly increased over venous (7.8 +/- 1.4 ng/l) in the supine position with an arteriovenous difference of 3.5 +/- 1.2 ng/l (p less than 0.05). After 30 min in the upright position, an average increment of 45% to 11.3 +/- 1.8 ng/l was observed for venous vasopressin. Since a similar increase was not found for arterial vasopressin, the arteriovenous difference decreased with 29% to 2.5 +/- 2.1 ng/l and was no longer statistically significant. The correlation between supine and standing vasopressin was statistically significant both for arterial (p less than 0.001) and venous plasma (p less than 0.05). These data indicate a substantial removal of plasma vasopressin by receptors even in the peripheral vascular beds (forearm) and not only in the liver and the kidneys as previous literature claims. The arteriovenous difference decreases in the upright position, most likely because of reduced plasma vasopressin clearance.

Increased plasma vasopressin and serum uric acid in the low renin type of essential hypertension.

In 22 50-year-old men with long-standing, untreated essential hypertension of the low renin type, venous plasma vasopressin concentrations were about three times those of 15 matched normotensive control subjects (p less than 0.005). These patients also had increased arterial concentrations of noradrenaline and adrenaline (p less than 0.05) but there was no direct association between these two catecholamines and vasopressin. On the other hand, adrenergic beta-receptor blockade with oxprenolol reduced both blood pressure and plasma vasopressin (p less than 0.01) while venous plasma dopamine concentrations significantly increased. In addition, the hypertensives had highly significantly increased serum uric acid (p less than 0.001) that correlated positively with venous vasopressin concentrations (p less than 0.05). According to these data, patients with the volume-sustained low renin type of essential hypertension have increased plasma vasopressin concentrations that probably are inversely related to dopaminergic nervous activity. The data also indicate that increased plasma vasopressin correlates with serum uric acid, most probably through increased tubular reabsorption of this acid.

The in vivo metabolism of C3 in human glomerulonephritis and after renal transplantation.

Metabolic investigations of complement component C3 have been performed to study pathogenetic mechanisms in patients with glomerulonephritis and after renal transplantation. Purified and biologically active 125I-labelled C3 was given intravenously together with 131I-albumin to nine patients with different forms of glomerulonephritis and nine allograft recipients at different stages after renal transplantation. Control studies were performed in 16 normal individuals. The fractional catabolic rate (FCR) of the proteins was calculated with the metabolic clearance method (U/P ratio) and/or by analysis of the plasma radioactivity disappearance curve. An increased FCR of C3 was found in three patients with glomerulonephritis. A modestly elevated FCR of C3 was found in all but one of the transplant patients as calculated by the U/P ratio, while the FCR was high in only two when calculated from plasma radioactivity disappearance. Slight increases of C3 catabolism were found during two suspected rejection episodes, but may have been due to a general increase in protein turnover. The serum level of C3 was reduced in two recipients and in one of these the FCR of the protein was elevated. The remaining patients had normal or increased C3 levels. Judged from these results, activation of complement was only of modest importance in the patients studied.

Influence of body weight on plasma catecholamine patterns in middle-aged, normotensive men.

To study the influence of body weight on plasma catecholamine patterns, 34 healthy, normotensive men aged 51 +/- 1 years were stratified into lean (n = 22) and overweight (n = 12) subjects according to Thomas' body mass index. No significant differences on supine arterial and venous catecholamines or standing venous adrenaline and dopamine appeared. However, the lean men had an increased orthostatic venous noradrenaline response (477 +/- 38 ng/l) compared to the overweight (319 +/- 46 ng/l, P less than 0.02). The present findings may indicate an inverse relationship between the sympathetic noradrenergic responsiveness and body weight in healthy, normotensive men while no differences were found in basal catecholamine levels.

Increased arterial catecholamine concentrations in 50-year-old men with essential hypertension.

In a recent study of 50-year-old men with long-standing, untreated essential hypertension we found increased arterial and venous plasma concentrations and arterial-venous differences of adrenaline (a-v) and noradrenaline (v-a) as compared to a matching normotensive control group. The aim of the present study was to investigate whether men of this age with hypertension of shorter duration and less severity than in the first study might also have increased plasma catecholamines. Twenty-three hypertensive and 17 age-matched normotensive control men were studied. The hypertensive ones had increased supine heart rate (P less than 0.05), arterial noradrenaline (P less than 0.01) and adrenaline (P less than 0.02) whereas venous catecholamines did not differ between the two groups. The a-v differences (means +/- SE) of adrenaline (78 +/- 14 vs 42 +/- 6 ng/l, P less than 0.05) were increased in the hypertensive compared to the normotensive group. In the hypertensive, the arterial plasma concentrations of the two catecholamines correlated positively (r = 0.71, P less than 0.001) as did the a-v differences (r = 0.54, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)