Effect of somatostatin on plasma renin activity and blood pressure in patients with essential hypertension

The effects of somatostatin on plasma renin activity (PRA) and blood pressure were evaluated in patients with essential hypertension (EH) and in normotensive subjects. All subjects examined were hospitalized and placed on a diet containing 7-8 g/day sodium chloride and received an intravenous infusion of somatostatin (500 microgram/20 ml of saline, for 60 min) in the basal condition. During somatostatin infusion, the mean blood pressure (MBP) remained unaffected in all patients with EH and the normotensive subjects, while the PRA decreased slightly in the EH group. When the patients with EH were classified according to their renin levels (low, normal and high), parallel significant decreases in MBP and PRA were found only in the high renin group during the somatostatin infusion. No significant change in MBP and PRA was observed in the other groups including the normotensive subjects. To assess the activity of synthetic somatostatin, the plasma levels of growth hormone (GH) and cyclic AMP were measured. These levels were lowered significantly during the infusion and the GH levels showed a rebound 15 min after cessation of the infusion. The cyclic AMP returned to the basal levels, but no rebound was observed. The above data indicate that the fall in blood pressure in the high renin group in the basal condition was probably due in part to reduced renin release by somatostatin, and the maintenance of high blood pressure especially in high renin EH.     

Immediate plasma renin response to propranolol: differentiation between essential and renal hypertension.

The immediate short-term effect on plasma renin activity of intravenous injection of propranolol was studied in 31 normal subjects and 166 hypertensive patients. In patients with essential hypertension and normal subjects plasma renin activity fell considerably within 15 minutes; the fall was directly proportional to initial plasma renin levels. In contrast, in patients with renal hypertension the fall was much less pronounced or totally absent. These differences in response to propranolol provide, though presently only on a group basis, a biochemical means of differentiating between patients with renal hypertension and those with essential hypertension. The observations also indicate that, unlike normal subjects and patients with essential hypertension, in patients with renal hypertension sympathetic activity plays no part in the control of basal plasma renin levels.     

Effect of exercise on plasma cyclic AMP

The purpose of this study was to confirm the relationship between cyclic AMP(cAMP) level in plasma and changes of hormones concentrations in blood, during and after physical exercise. The results were as follows: At rest, plasma cAMP were 23.1 p mole/ml on the average and decreased after glucose loading. The level in plasma increased in proportion to the intensity of exercises. Under the 50% condition of the maximal intensity, cAMP level in plasma was about 40 p mole/ml and the contents of both thyroxine and growth hormone in serum clearly increased. And, under the 70% of the maximal, the contents of both adrenaline and noradrenaline in serum as well as that of cAMP in plasma increased. Plasma cAMP level also increased by prolongation of exercise (ca 45 p mole/ml). And when exercise lasted over 1.5 hrs, plasma glucagon level began to rise. The effect of carbohydrate load to lower the levels of plasma cAMP were also found during physical exercise. These results suggested that the cAMP level in plasma was affected, not only by the some regulating factors of glycolytic activities such as adrenaline and glucagon, but also by the production of thyroxine and growth hormone at the onset of exercise.     

Effect of propranolol on plasma renin activity, renal cortex renin, and adrenal and brain isorenins in rats.

Propranolol administration to rats was studied for its effects on plasma renin activity, renal renin content, and adrenal and brain isorenins. Propranolol was given intraperitoneally at 6 and 30 mg/kg/day for a 15-day period. Pulse rate was significantly decreased. There were no effects on the isorenin content of adrenal or brain tissue or on renal renin content. Rats responded in two completely different ways with respect to plasma renin activity. Two-fifths had a total suppression of plasma renin activity; the rest had concentrations similar to those in controls. These observations are consistent with those seen during chronic administration of propranolol to hypertensive patients and suggest that its antihypertensive effect may in some patients be through the suppression of renin release. Its mechanism of action in most patients remains at present unclear.     

Plasma leptin levels strongly correlate with plasma renin activity in patients with essential hypertension.

Previous studies demonstrated elevated plasma leptin and angiotensinogen (PRA) levels in essential hypertension. However, a few studies investigated the relationship between leptin and angiotensinogen levels in both lean and overweight/ obese hypertensives. The aim of the present study was therefore to examine the relationship between blood pressure, leptin and plasma renin activity in normotensives and in both lean and overweight/obese patients with essential hypertension. Two groups of subjects who were carefully matched for age, gender, waist:hip ratio and body mass index (BMI) were studied: 28 normotensives (NT) (age: 40.1+/-9.1 years old, BMI: 28.1+/-3.6 kg/m2, male/female: 18/10) and 33 newly diagnosed mild to moderate essential hypertensives (EHT) (age: 38.9+/-10 years old, BMI: 27.9+/-4.8 kg/m2, male/female: 22/11). No significant differences in age, gender, waist:hip ratio, fasting blood glucose and BMI were detected between EHT and NT groups. However, systolic and diastolic pressures, mean arterial blood pressures, plasma leptin levels and PRA were significantly higher in EHT group than in NT group (P = 0.001). Plasma leptin levels were strongly correlated with BMI in EHT (r=0.67, P = 0.001) and NT groups (r=0.44, P = 0.001). Plasma leptin levels were correlated with plasma PRA levels in both EHT and NT groups (r = 0.66 and r = 0.44; both P < 0.05, respectively). There was no correlation between leptin or PRA and systolic, diastolic pressures, or mean arterial blood pressures. Furthermore, the patients were divided as lean (n=16) and overweight/obese (n = 17) and compared with BMI-matched controls. In both subgroups, plasma leptin and PRA levels were also higher than those of controls. Our results showed that elevated plasma leptin and PRA are associated with hypertension in both lean and overweight/obese hypertensives. Moreover, plasma leptin was significantly correlated with plasma angiotensinogen levels. These findings suggest that adipose mass is an important determinant of blood pressure, although the mechanism is not clear.     

Effect of clonidine on three types of experimental hypertension and on plasma renin activity in dogs]

Intra-cisternal clonidine (3 microgram/kg) reduced hypertension and cardiac acceleration after defrenation in dogs, but did not act in intra-venous infusion (10 microgram/kg). The renin activity was not modified. Clonidine was always inactive on hypertension after stimulation of visceral afferences or after injection of potassium cyanidine. These results show that a central mechanism was implied in the anti-hypertensive action of clonidine.     

Effect of somatostatin on plasma renin activity.

Intravenous infusion of somatostatin in mongrel dogs caused a significant decrease in the peripheral plasma renin activity (PRA) enhanced by pentobarbital sodium anesthesia or furosemide treatment. However, the inhibitory activity vanished within 10 min after termination of somatostatin infusion. Intrarenal arterial infusion of somatostatin decreased furosemide-enhanced PRA in renal vein by 24.0%, 16.6% and 8.6% in dose of 0.1, 0.5 and 1.0 microgram, respectively. On the other hand, high doses of the peptide (50-200 microgram) failed to decrease. The changes in PRA occurred in the absence of any alteration in blood pressure during the intravenous infusion under furosemide treatment. In an in vitro study, the addition of somatostatin in doses of 0.01 and 0.05 microgram suppressed the renin release in dog renal cortical cell suspension by 74.3% and 53.6%, respectively. Therefore, in both intrarenal arterial infusion and the cell suspension system, somatostatin was increasingly effective in decreasing renin release towards the lower end of the dose range tested. These results suggest that the effect of somatostatin on hyperreninemia may involve an inhibition of renin release at the cell level in the kidney.     

Aldosterone and renin in essential hypertension.

A review of some recent laboratory findings indicates definite disturbances in aldosterone metabolism and regulation in patients with mild essential hypertension: (a) a significant mean increase in plasma aldosterone concentration in patients with mild and stable essential hypertension, in contrast to the absence of any difference in patients with labile borderline essential hypertension when in a normotensive phase, compared with control subjects; and (b) a significant mean decrease in metabolic clearance rate of aldosterone, associated with a 12% decrease in hepatic blood flow and an increased binding of aldosterone to a transcortin-like plasma globulin. The secretion rate of 18-hydroxy-11-deoxycorticosterone is above the upper range of normal in 60% of patients with mild, uncomplicated essential hypertension. The incidence of low-renin hypertension, when age and race are taken into account, is much lower than previously assumed. Unless measurements are repeated over a long period, one or two low values of plasma renin cannot be considered a permanent marker indicating a special category of patients with essential hypertension. Tonin, a new enzyme discovered by Boucher, which forms angiotensin II directly from a plasma protein, from the tetradecapeptide substrate and from angiotensin I, is present in most tissues, but in highest concentration in the submaxillary gland. This enzyme is under the control of beta-adrenergic receptors.     

Radioactive 86rubidium influx into red blood cells in essential hypertension in relation to the plasma renin activity

Changes in several mechanisms of sodium transport across the cell membranes are described in essential hypertension. We studied ouabain-sensitive and insensitive 86Rb+ influx into the red blood cells (RBC) of 16 healthy controls and 51 patients with essential hypertension (EH) divided according to their plasma renin activity (PRA) in 3 groups: 11 patients with high PRA (HREH), 18 patients with normal PRA (NREH) and 22 patients with low PRA (LREH). In addition to studying 86RB+ uptake by patients RBC, we tested also the effect of the patients' sera on 86Rb+ influx into the RBC of healthy subjects. Red blood cells of patients with HREH and NREH had lower ouabain-sensitive 86Rb+ influx in comparison with controls. No significant differences were found between these hypertensive groups. In contrast 86Rb+ uptake by the RBC of LREH patients was always higher than in controls or HREH and NREH. It was chiefly the ouabain-sensitive component that was raised, but some increase in ouabain-insensitive 86Rb+ influx also could be seen. The serum of patients with HREH and NREH, when incubated with RBC of healthy controls, lowered their ouabain-sensitive 86Rb+ influx. The decrease was more pronounced in NREH than in HREH group. Plasma from LREH patients increased both ouabain-sensitive and ouabain-insensitive 86Rb+ influx into the control RBC. These findings indicate that there may be differences in the sodium/potassium transport mechanisms across the cell membrane in various kinds of EH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of parathyroid hormone on plasma renin activity in humans

The effect of PTH infusion on PRA was evaluated in 22 normotensive subjects. Intravenous infusion of PTH produced an increase in PRA in studied subjects. This increase in PRA was dose dependent from 1.505 +/- 0.226 to 2.500 +/- 0.346 nmol/l/hour after administration of 100 units of PTH and from 1.648 +/- 0.189 to 4.294 +/- 0.614 nmol/l/hour after 200 units of PTH and was markedly decreased by a beta blocking drug from 1.660 +/- 0.259 to 2.498 +/- 0.485 nmol/l/hour. These responses were observed without any significant changes in plasma calcium and blood pressure. From our results we can conclude that PTH increases PRA in normotensive controls. This effect is partly blocked by beta adrenergic blockers.     

Calcium metabolism in essential hypertension: relationship to altered renin system activity

Hypertensive disease is associated with various abnormalities of calcium metabolism although how these abnormalities relate to the elevated pressure remains unclear. Based on the use of renin-sodium profiling, we have defined heterogeneous deviations in circulating levels of ionized calcium and magnesium as well as of the calcium-regulating hormones parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D (1,25D), which parallel similar deviations in plasma renin activity. Essential hypertensive subjects with a profile of low renin, lower ionized calcium, and elevated 1,25D respond best to the calcium channel blocker nifedipine, demonstrate an enhanced sensitivity to the blood pressure effects of dietary salt loading, and have significantly lower blood pressures in response to oral calcium supplementation. Hypertensive subjects with the opposite metabolic profile--higher renin activity, higher serum ionized calcium, and lower 1,25D levels--are relatively insensitive to the blood pressure effects of either dietary salt loading or nifedipine, and show no significant hypotensive response to calcium supplements. Altogether, these alterations of calcium ionic and hormonal metabolism suggest that the hormonal control of calcium metabolism is linked to renin system activity as well as to the pathophysiology of the hypertensive process.     

Effect of dopamine and dopamine-receptor blockade on in vitro renin release, tissue renin content and tissue cyclic AMP content in the rat

This study evaluated the in vitro renin release, tissue cyclic AMP content (TcAMPc), and tissue renin content (TRC) changes with time, in response to administration of dopamine (DOP) and of the dopamine-receptor blocking agent pimozide (PIM) to renal cortical slices from sodium deficient (SD) rats. Addition of 10(-3)M DOP to the slice preparation resulted in a gradual stimulation of RR with time, which was significantly different from that seen in control samples after 60 min of incubation. In contrast, TcAMPc of the DOP-treated samples was significantly greater than that of controls after 5 min of incubation. At 60 min, mean TRC of DOP-treated samples was greater than that of controls but not significantly. Two PIM doses (10(-8)M and 10(-6)M, whether added alone or together with 10(-3)M DOP to the cortical slice system, significantly increased RR in each instance while simultaneously depressing TcAMP content markedly below that of unstimulated controls at all incubation times examined. Mean TRC of pimozide-treated samples was also lower than that of controls by 60 min. These in vitro data in the SD rat suggest that: 1) stimulation of renin release by DOP is time-dependent and is mediated by a TcAMP-generating mechanism, and 2) the increase in renin release by PIM administration appears to involve pharmacological inactivation of TcAMP-generating pathways and disruption of membrane permeability, leading to uncontrolled RR.