"Salt-sensitive" essential hypertension in men. Is the sodium ion alone important?

We investigated whether the anionic component of an orally administered sodium salt can influence the salt's capacity to increase blood pressure. In five men with essential hypertension in whom blood pressure was normal with restriction of dietary sodium chloride to 10 mmol per day (0.23 g of sodium per day), oral administration of sodium chloride for seven days, 240 mmol per day (5.52 g of sodium per day), induced significant increases in systolic and diastolic blood pressures, of 16 +/- 2 and 8 +/- 2 mm Hg (mean +/- SEM), respectively (P less than 0.05). An equimolar amount of sodium given as sodium citrate induced no change in blood pressure. Replacing supplemental sodium chloride with an equimolar amount of sodium as sodium citrate abolished the increase in blood pressure induced by sodium chloride. Both salts induced substantial and comparable sodium retention, weight gain, and suppression of plasma renin activity and plasma aldosterone, but supplemental sodium chloride increased plasma volume and urinary excretion of calcium, whereas sodium citrate did not. These preliminary findings demonstrate that the anionic component of an orally administered sodium salt can influence the ability of that salt to increase blood pressure, possibly by determining whether the salt induces an increase in plasma volume. Our observations in a small group of men with salt-sensitive hypertension will require confirmation in larger numbers of patients of both sexes.     

Atrial natriuretic peptide, renin activity, aldosterone, urine volume and electrolytes during a 24-h sleep-wake cycle in man

To investigate the diurnal variation in the plasma atrial natriuretic peptide (ANP) concentrations and its relation to renin activity, aldosterone, urine volume and electrolytes, blood samples from six healthy male subjects were collected and blood pressure and heart rate recorded every 4 h during a 24-h sleep-wake period. Systolic blood pressure and heart rate were at the lowest during sleep. Plasma ANP, extracted on Sep-Pak cartridges and measured by radioimmunoassay, had the highest concentration at midnight and lowest at 04.00 h (27 +/- 18 vs 16 +/- 18 ng l-1, mean +/- SD, P less than 0.05 after normalization of the original values). Plasma renin activity and aldosterone were at the highest at 08.00 and 12.00 h, whereafter they both began to decrease (P less than 0.001, also normalized). Urinary volume, sodium, potassium and chloride showed highest values (P less than 0.05) between 08.00 and 16.00 h. Plasma ANP levels did not correlate with systolic blood pressure, heart rate, serum or urinary Na or plasma renin or aldosterone (r = 0.1-0.3, P greater than 0.05). Plasma renin activity correlated with aldosterone and aldosterone with urinary K (r = 0.66 and 0.58 respectively, P less than 0.001). These results suggest that the low plasma ANP levels found in our subjects at 04.00 h may be associated to diminished atrial distension accompanied by the inactivity of the sleep period. In addition, ANP does not appear to affect the secretion of renin and aldosterone in a normal sleep-wake cycle.     

Body composition, intraerythrocyte sodium content, volume regulation and blood pressure during moderate sodium restriction in hypertensive men

Eleven moderately obese middle-aged male outpatients with untreated mild hypertension reduced their sodium intake by about 120 mmol per day during 4-6 weeks. Diastolic blood pressure was then significantly reduced in comparison with a matched control group. The reduction of urinary sodium excretion was significantly correlated to the change in mean arterial pressure. Mean body mass showed a small significant decrease, although there were no significant changes in total body water or body fat as determined from measurements of 40K and tritiated water. Nor did mean extracellular water or plasma volume (Evan's blue) show any significant change. The decrease in urinary sodium excretion was associated with increases in plasma renin activity and urinary aldosterone excretion, while a sympathetic nervous natriuretic index (urinary dopamine to noradrenaline excretion ratio) decreased. The low sodium diet period was followed by a period of energy reduction as well as sodium restriction for 15 weeks. Mean body mass was then reduced by about 8 kg. The systolic but not the diastolic blood pressure showed a significant decrease. The intraerythrocyte content of water, sodium and potassium did not change significantly during any of the diet periods. We conclude that moderate sodium restriction lowered the blood pressure and affected the renin-aldosterone and sympathetic nervous system to retain sodium which might explain the constancy of the plasma volume.     

Plasma catecholamines and renin during operant blood pressure conditioning in baboons

Plasma catecholamines and renin activity were measured in baboons undergoing operant diastolic blood pressure conditioning. Pre-training baseline norepinephrine averged 364 pg/ml, epinephrine 253 pg/ml, dopamine 270 pg/ml, and renin activity 2.62 ng/ml/hr. During the training sessions, systolic blood pressure increased significantly 19 mmHg (15%), diastolic pressure 20 mmHg (30%), and heart rate 33 bpm (33%) compared with pre-session values. Also during the sessions, norepinephrine increased significantly by 253 pg/ml (48%) and epinephrine increased by 130 pg/ml (0.05<p<0.10), while plasma dopamine and renin activity did not change significantly. Plasma norepinephrine levels correlated positively with systolic and diastolic blood pressures in all baboons tested, in both baseline and training conditions. To the extent that plasma norepinephrine reflects sympathetic nervous system activity, these findings demonstrate an association between sympathetic activity and blood pressure in this hypertensive model.     

The effect of a protein-free diet on the renin-angiotensin system in the rat

Summary The effects of a protein-free diet were studied in the rat. It was shown that the diet led to a decrease in total serum protein, in plasma renin activity, in plasma renin substrate and in blood pressure; and to an increase in haematocrit.A significant linear correlation was found in every combination between the total serum protein, plasma renin activity, plasma renin substrate and systolic blood pressure.In contrast to the plasma renin activity, the renin concentration in the kidney of rats on a protein-free diet was found not to be lower that of the control group.The protein-free diet caused a decrease in the pressor response to injected angiotensin II.     

Psychotherapeutic control of hypertension.

We conducted a six-month trial to determine the effect of psychologic relaxation on blood pressure. Alterations of peripheral sympathetic-nervous-system activity, as reflected by changes of dopamine-beta-hydroxylase in plasma, were evaluated, and plasma volume and plasma renin activity were measured. Treated patients exhibited significant (P less than 0.05) reductions of blood pressure when supine and upright, and of plasma dopamine-beta-hydroxylase activity, and furosemide-stimulated renin activity when upright. Blood-pressure changes after six months correlated best with differences in plasma activity of dopamine-beta-hydroxylase with patients supine (r = 0.54; P less than 0.05) and upright (r = 0.62; P less than 0.05). These results suggest that reduction of peripheral adrenergic activity contributes importantly to the improvement of hypertension observed with this form of therapy. Furthermore, the decrease of furosemide-stimulated plasma renin activity suggests that alterations of the renin-angiotensin system may help lower blood pressure in certain patients.     

Prostaglandins are involved in the stimulation of renin gene expression in 2 kidney-1 clip rats

This study was done to obtain information about a possible involvement of prostaglandins in the renal baroreceptor mechanism regulating renin secretion and renin gene expression. To this end the effect of the cyclooxygenase inhibition was examined on renin secretion and on renal renin gene expression in 2 kidney-1 clip rats. The influences of the cyclooxygenase inhibitors indomethacin (2mg/kg twice a day) and meclofenamate (8 mg/kg twice a day) on renal renin m-RNA levels, on plasma renin activity (PRA) and on blood pressure were measured 2 days after clipping the left renal arteries of male Sprague-Dawley rats with 0.2 mm clips. In sham-clipped animals, indomethacin and meclofenamate had no significant effect on basal PRA and renin m-RNA levels. In vehicle-treated animals unilateral renal artery clipping increased blood pressure from 120±4.1 to 150±6.1 mmHg, increased PR6A from 7.4±1.6 to 27.6±3.8 as expressed in nanograms of angiotensin I per hour per millilitre, increased renin m-RNA levels of clipped kidneys from 105±5.9% of standard to 482.6±56% of standard and decreased renin m-RNA levels of contralateral kidneys from 116±9.7% of standard to 34±9.0% of standard. While blood pressure, PRA and renin m-RNA levels of the contralateral kidneys were virtually unchanged by the cyclooxygenase inhibitors indomethacin and meclofenamate, renin gene expression in the clipped kidney was markedly influenced by inhibition of prostaglandin synthesis. Both cyclooxygenase inhibitors attenuated the increase of renin m-RNA levels in response to clipped to 280±26% of standard and 261±35% of standard after application of indomethacin or meclofenamate. These findings suggest that intact prostaglandin formation is at least partially required for the stimulatory effect of low renal perfusion pressure on renin gene expression.     

Circulatory changes and renin secretion in sheep in response to feeding

1. The effect of feeding on the circulation, on renin release and on renal function has been examined in the sheep.2. There was a rapid reduction of plasma volume within 15 min of starting to eat dry feed.3. This was accompanied by an abrupt rise in systolic blood pressure and by a more gradual and prolonged elevation of heart rate.4. Within 30 min of feeding there occurred renal conservation of sodium and water which continued for at least 2-3 hr.5. Renin was released into the circulation of sheep that ate rapidly; slow feeders did not show this response.6. The rise in plasma renin concentration was inhibited by infusing a solution similar in composition to mixed saliva at a rate that prevented the change in plasma volume.7. It is concluded that the rapid transfer of sodium and water from the circulation to the rumen via the saliva during ingestion of dry feed is sufficient to activate the renin/angiotensin system.     

Effects of exogenous renin and sodium load on renin activity in unilaterally nephrectomized rats

Summary Effects of injection of homologous renin and sodium load given through 1.5% saline as drinking water on plasma renin activity and renin content of the kidneys were studied in rats with intact kidneys (group A) and in unilaterally nephrectomized rats (group B). During an experimental period of 10 days, blood pressure was measured four times. At the end of the experiment, the plasma renin activity and the renal content of renin were determined.Renin injection did not cause a rise in blood pressure in both groups. In unilaterally nephrectomized rats, renin content of the remaining kidney increased significantly. This increase was suppressed either by the renin injection or the salt load, whereas neither the renin injection not the salt load affected renal content of renin in group A. In unilaterally nephrectomized rats, the renin injection or the sodium load induced a significant decrease in plasma renin activity when compared to rats in group A.     

Normotension,hypertension and body fluid regulation: brain and kidney

The fraction of hypertensive patients with essential hypertension (EH) is decreasing as the knowledge of mechanisms of secondary hypertension increases, but in most new cases of hypertension the pathophysiology remains unknown. Separate neurocentric and renocentric concepts of aetiology have prevailed without much interaction. In this regard, several questions regarding the relationships between body fluid and blood pressure regulation are pertinent. Are all forms of EH associated with sympathetic overdrive or a shift in the pressure–natriuresis curve? Is body fluid homoeostasis normally driven by the influence of arterial blood pressure directly on the kidney? Does plasma renin activity, driven by renal nerve activity and renal arterial pressure, provide a key to stratification of EH? Our review indicates that (i) a narrow definition of EH is useful; (ii) in EH, indices of cardiovascular sympathetic activity are elevated in about 50% of cases; (iii) in EH as in normal conditions, mediators other than arterial blood pressure are the major determinants of renal sodium excretion; (iv) chronic hypertension is always associated with a shift in the pressure–natriuresis curve, but this may be an epiphenomenon; (v) plasma renin levels are useful in the analysis of EH only after metabolic standardization and then determination of the renin function line (plasma renin as a function of sodium intake); and (vi) angiotensin II‐mediated hypertension is not a model of EH. Recent studies of baroreceptors and renal nerves as well as sodium intake and renin secretion help bridge the gap between the neurocentric and renocentric concepts.     

Properties of the macula densa mechanism for renin release in the dog

To study the macula densa mechanism for renin release, both the macula densa and the haemodynamic mechanisms were activated in anaesthetized dogs with denervated kidneys, either by renal arterial constriction to a renal arterial pressure (RAP) of 52 +/- 2 mmHg or by ureteral occlusion to a ureteral pressure of 95-105 mmHg, 20-25 mmHg below RAP. Renal arterial constriction increased renin release from 0.3 +/- 0.2 to 16 +/- 4 micrograms AI min-1. At low RAP, renin release was subsequently reduced to 7 +/- 3 micrograms AI min-1 when sodium excretion was raised far above control values by plasma volume expansion and acetazolamide infusion. Ethacrynic acid (3 mg kg-1 body wt.) restored renin release to pre-expansion values, and a large dose (25 mg kg-1 body wt.) prevented renin release from falling even after unclamping the artery. During ureteral occlusion with stopped glomerular filtration, plasma volume expansion, acetazolamide and ethacrynic acid infusion did not alter renin release. On the other hand, beta-adrenergic stimulation by isoproterenol raised renin release equally (by 30-40 micrograms AI min-1) before and after plasma volume expansion, during both renal arterial constriction and ureteral occlusion. Indomethacin (10 mg kg-1 body wt.) abolished renin release induced by ethacrynic acid infusion and ureteral occlusion. We conclude that the macula densa mechanism for renin release is inactivated by high NaCl reabsorption during plasma volume expansion and acetazolamide infusion, reactivated by inhibition of NaCl reabsorption with ethacrynic acid and completely inhibited by indomethacin. The degree of activation does not influence the renin release induced by beta-adrenergic stimulation.     

Trophic effects of hypophyseal hormones on resistance vessels and the heart in normotensive and renal hypertensive rats.

Arterial pressure is an important determinant of cardiovascular structure and relates positively to it. The purpose of this study was to determine whether pituitary hormones influence the relation of pressure and structure. Male Sprague-Dawley rats, aged 5 weeks, were studied in three groups: the first underwent hypophysectomy; the second was hypophysectomized but received replacement therapy with growth hormone and thyroxine; the third served as controls. Four days later half of each group underwent unilateral renal artery clipping, the other half serving as normotensive controls. For 5 weeks estimates were made of systolic blood pressure, heart rate, body weight and plasma renin activity. Rats were then killed; left ventricular, kidney and adrenal weights were determined and, using hindquarter perfusion, estimates were made of resistance at maximal dilatation (reflecting inner radius), and of maximal pressor response (reflecting wall thickness). Results: (1) Hypophysectomy in non-clipped rats reduced growth rate, systolic blood pressure and heart rate while plasma renin activity rose. As related to pressure and to body weight, resistance at maximal dilatation, maximal pressor response, left ventricular weight remained at the juvenile values of a 5-week-old rat. Hormone replacement restored values to those of control rats aged 11 weeks. (2) Clipping in the control group rats increased systolic blood pressure more than in hypophysectomized and growth hormone and thyroxine receiving hypophysectomized groups even though plasma renin activity remained higher in hypophysectomized than in control rats. Plasma renin activity was highest in hypophysectomized rats with highest pressure. (3) Systolic blood pressure related positively to left ventricle weight, resistance at maximal dilatation, maximal pressor response and calculated wall thickness to inner radius ratios in all groups. However, these regressions were all, like renal structural adaptation, considerably depressed in the hypophysectomized group. Hormone replacement restored the relation of structure and pressure towards that of control group rats. Thus, growth hormone and thyroxine influence maturation of the normal cardiovascular system and greatly enhance its structural upward resetting in hypertension.     

Renal renin secretion as regulator of body fluid homeostasis

The renin–angiotensin system is essential for body fluid homeostasis and blood pressure regulation. This review focuses on the homeostatic regulation of the secretion of active renin in the kidney, primarily in humans. Under physiological conditions, renin secretion is determined mainly by sodium intake, but the specific pathways involved and the relations between them are not well defined. In animals, renin secretion is a log-linear function of sodium intake. Close associations exist between sodium intake, total body sodium, extracellular fluid volume, and blood volume. Plasma volume increases by about 1.5 mL/mmol increase in daily sodium intake. Several lines of evidence indicate that central blood volume may vary substantially without measurable changes in arterial blood pressure. At least five intertwining feedback loops of renin regulation are identifiable based on controlled variables (blood volume, arterial blood pressure), efferent pathways to the kidney (nervous, humoral), and pathways operating via the macula densa. Taken together, the available evidence favors the notion that under physiological conditions (1) volume-mediated regulation of renin secretion is the primary regulator, (2) macula densa mediated mechanisms play a substantial role as co-mediator although the controlled variables are not well defined so far, and (3) regulation via arterial blood pressure is the exception rather than the rule. Improved quantitative analyses based on in vivo and in silico models are warranted.     

Blood volume, blood pressure and total body sodium: internal signalling and output control

Total body sodium and arterial blood pressure (ABP) are mutually dependent variables regulated by complex control systems. This review addresses the role of ABP in the normal control of sodium excretion (NaEx), and the physiological control of renin secretion. NaEx is a pivotal determinant of ABP, and under experimental conditions, ABP is a powerful, independent controller of NaEx. Blood volume is a function of dietary salt intake; however, ABP is not, at least not in steady states. A transient increase in ABP after a step-up in sodium intake could provide a causal relationship between ABP and the regulation of NaEx via a hypothetical integrative control system. However, recent data show that subtle sodium loading (simulating salty meals) causes robust natriuresis without changes in ABP. Changes in ABP are not necessary for natriuresis. Normal sodium excretion is not regulated by pressure. Plasma renin is log-linearly related to salt intake, and normally, decreases in renin secretion are a precondition of natriuresis after increases in total body sodium. Renin secretion is controlled by renal ABP, renal nerve activity and the tubular chloride concentrations at the macula densa (MD). Renal nerve activity is related to blood volume, also at constant ABP, and elevates renin secretion by means of beta(1)-adrenoceptors. Recent results indicate that renal denervation reduces ABP and renin activity, and that sodium loading may decrease renin without changes in ABP, glomerular filtration rate or beta(1)-mediated nerve activity. The latter indicates an essential role of the MD mechanism and/or a fourth mediator of the physiological control of renin secretion.     

Effects of hypoproteinemia on fluid volumes and arterial pressure

The effects of both moderate and large decreases in plasma protein concentration on arterial pressure and fluid volumes were studied in 23 conscious dogs. In experiment 1, plasma protein concentration decreased 33% during a 5-day plasmapheresis period. During this time sodium space increased 11%, mean arterial pressure decreased slightly, and neither blood volume nor plasma volume decreased. Experiment 2 was performed to see if blockade of the alpha-sympathetic and angiotensin systems could prevent the blood volume homeostasis during moderate hypoproteinemia. Sodium space increased; however, blood volume was unchanged. During experiment 3 plasma protein concentration decreased 68% over a 12-day plasmapheresis period. By the last day of plasmapheresis, plasma protein concentration was 2.4 g/100 ml, mean arterial pressure had decreased 26 mmHg, sodium space had increased 12%, plasma renin activity had increased 11-fold, and blood volume and plasma volume were 63.9 +/- 4.0 and 66.9 +/- 2.5% of control, respectively. We conclude that the maintenance of a normal blood volume during moderate hypoproteinemia does not require active participation of the renin-angiotensin and alpha-sympathetic systems and large decreases in plasma protein concentration are accompanied by marked hypovolemia, hypotension, and hyperreninemia.     

Renin secretion in the earliest stage of goldblatt-type hypertension in rats

Summary Unilateral nephrectomy and constriction of the remaining renal artery in the rat induced a sustained increase of systolic blood pressure, which becomes significant as soon as 90 minutes after operation, and a transient rise in renal venous as well as in peripheral plasma renin activity between 20 and 180 minutes after operation. Unilateral nephrectomyper se, after 90 and 180 minutes, caused a significant fall of the systolic blood pressure, a slight increase of renal venous renin activity after 20 and 45 minutes, and between 3 and 24 hours after operation it was followed by a significant decrease of peripheral plasma renin activity. An increased secretion of renin from the clamped kidney may thus contribute to the initial rise of blood pressure in rats with Goldblatt-type hypertension.Supported by Fonds National Suisse de la Recherche Scientifique, Grant No. 53153.     

Effects of sodium intake on plasma potassium and renin angiotensin aldosterone system in conscious dogs

AIMS: The operating range of the renin-angiotensin-aldosterone system is ill-defined. This study quantifies renin-angiotensin-aldosterone system activity as a function of sodium intake. METHODS: Renin-angiotensin-aldosterone system variables were measured daily after a sudden reduction in sodium intake (3.0-0.5 mmol kg(-1) day(-1)) or at steady states generated by eight levels of sodium intake (0.5-8.0 mmol kg(-1) day(-1)). Potassium intake was 2.79 +/- 0.03 mmol kg(-1) day(-1). Arterial blood pressure was measured invasively. Hormone concentrations were determined by radioimmunoassays. Glomerular filtration rate and plasma volume were determined by standard methods. RESULTS: Sudden sodium intake reduction doubled plasma renin activity and angiotensin II, and tripled aldosterone on day 1 with only small non-significant additional changes on the following days. Different levels of sodium intake did not affect arterial blood pressure, heart rate, and plasma concentrations of sodium, angiotensinogen, atrial natriuretic peptide, vasopressin, glomerular filtration rate and diuresis. With increasing sodium intake, plasma volume increased by 0.47 +/- 0.04 mL (kg body mass)(-1) (unit increase in Na intake)(-1) (P < 0.01), and plasma potassium decreased with the slope -0.038 mm [(mmol Na+ intake) (kg body mass)(-1) day(-1)](-1) (P = 0.001) while plasma renin-activity, angiotensin II, and aldosterone decreased systematically as expected. CONCLUSIONS: A step reduction in sodium intake alters renin-angiotensin-aldosterone system activity on day 1 with little further change the subsequent 4 days. Week-long increases in sodium intake decreases renin-angiotensin-aldosterone system activity, increases plasma volume, and decreases plasma potassium. Isolated decreases in sodium intake increase aldosterone secretion via volume-mediated action on the renin-angiotensin system and via increases in plasma potassium.     

The effect of renal sympathectomy on blood pressure and plasma renin activity in spontaneously hypertensive and normotensive rats

Renal denervation delays the development of hypertension in spontaneously hypertensive (SH) rats. The influence of bilateral surgical renal sympathectomy, verified by fluorescence microscopy, on blood pressure and plasma renin activity in SH and normotensive rats (170–180 g before the sympathectomy) was studied. Neither in SH nor in normotensive rats, did the preoperative systolic blood pressure in the renal-sympathectomized group differ from that in the sham-operated controls. After the sympathectomy, blood pressure in the SH rats increased in 4 weeks only insignificantly, from 160±3 to 172±6 mmHg, while that in the sham-operated SH rats rose from 163±5 to 191±5 mmHg. In normotensive rats, blood pressures in both the renal-sympathectomized and sham-operated groups remained at the pre-operative levels. Thirty days after the operations, plasma renin activity or plasma kininogen in the renal-sympathectomized group did not differ from that in the sham-operated one either in SH or in normotensive rats. The results suggest that the delay in hypertension development produced by renal sympathectomy in SH rats is not mediated by a reduction in renin secretion.     

Human physiological responses to immersion into water of different temperatures

To differentiate between the effect of cold and hydrostatic pressure on hormone and cardiovascular functions of man, a group of young men was examined during 1-h head-out immersions in water of different temperatures (32°C, 20°C and 14°C). Immersion in water at 32°C did not change rectal temperature and metabolic rate, but lowered heart rate (by 15%) and systolic and diastolic blood pressures (by 11%, or 12%, respectively), compared to controls at ambient air temperature. Plasma renin activity, plasma cortisol and aldosterone concentrations were also lowered (by 46%, 34%, and 17%, respectively), while diuresis was increased by 107%. Immersion at 20°C induced a similar decrease in plasma renin activity, heart rate and systolic and diastolic blood pressures as immersion at thermoneutrality, in spite of lowered rectal temperature and an increased metabolic rate by 93%. Plasma cortisol concentrations tended to decrease, while plasma aldosterone concentration was unchanged. Diuresis was increased by 89%. No significant differences in changes in diuresis, plasma renin activity and aldosterone concentration compared to subjects immersed to 32°C were observed. Cold water immersion (14°C) lowered rectal temperature and increased metabolic rate (by 350%), heart rate and systolic and diastolic blood pressure (by 5%, 7%, and 8%, respectively). Plasma noradrenaline and dopamine concentrations were increased by 530% and by 250% respectively, while diuresis increased by 163% (more than at 32°C). Plasma aldosterone concentrations increased by 23%. Plasma renin activity was reduced as during immersion in water at the highest temperature. Cortisol concentrations tended to decrease. Plasma adrenaline concentrations remained unchanged. Changes in plasma renin activity were not related to changes in aldosterone concentrations. Immersion in water of different temperatures did not increase blood concentrations of cortisol. There was no correlation between changes in rectal temperature and changes in hormone production. Our data supported the hypothesis that physiological changes induced by water immersion are mediated by humoral control mechanisms, while responses induced by cold are mainly due to increased activity of the sympathetic nervous system. Accepted: 4 February 1999     

The effect of sodium load on the development of hypertension, plasma renin and kininogen in rats with renal artery constriction

Effects of sodium load on the development of hypertension, plasma renin activity (PRA) and kininogen were studied in rats with renal artery constriction and untouched contralateral kidney. After the operation or sham-operation, 0.9% NaCl or water were given as drinking fluid. A marked hypertension (systolic pressure greater than 150 mmHg) developed in all operated rats on saline, but only in 2/3 of operated rats on water. In none of the sham-operated controls did systolic pressure exceed 150 mmHg during 7 postoperative weeks. Within the operated group on water, hypertensive rats had significantly higher PRA values than normotensive animals (P less than 0.05). Salt load slightly suppressed the PRA in sham-operated rats but not in animals with constriction renal artery, compared to sham-operated controls on water. The operated rats on salt excess had higher plasma kininogen levels than the operated normotensive rats on water (P less than 0.05), but there were no other significant differences in kininogen values between different study groups, regardless of whether blood pressure was increased or not. The results indicate that in this form of hypertension, the high blood pressure can be maintained without any increase in PRA if animals are subjected to a sodium load which sensitizes vascular beds to angiotensin. The increase in plasma kininogen, suggesting suppression of kallikrein-kinin system, is unlikely associated with the increase of blood pressure.