Consequences of renal morphologic damage induced by inhibition of converting enzyme in rat renovascular hypertension

The consequences of morphologic changes in the kidney distal to a stenosis induced by chronic administration of a converting enzyme inhibitor were determined after induction of experimental renovascular hypertension in rats. The relationship between changes in morphology in the clipped kidney and diuresis, creatinine, and mortality was studied by converting a two-kidney, one-clip model into a one-kidney, one-clip model after 1 month of converting enzyme inhibition. The right renal artery was constricted with a clip of 0.2 mm diameter to increase blood pressure, the left kidney was left untouched. After 1 month, systolic blood pressure had increased to 173 +/- 27 mm Hg in the clipped animals (n = 47) compared with 139 +/- 8 mm Hg in sham-operated animals (n = 15; group 1). An inhibitor of angiotensin-converting enzyme, MK421 (2 mg/kg, po), or an equivalent volume of vehicle was then administered daily for 1 month. After treatment with the converting enzyme inhibitor, blood pressure (148 +/- 28 mm Hg) was virtually identical with that of a sham-operated, vehicle-treated control group (145 +/- 16 mm Hg, n = 15), and was significantly lower than that of untreated hypertensive rats (186 +/- 30 mm Hg, n = 17) (group 2). The weight of the left kidney was increased in the untreated hypertensive animals as compared with sham-operated controls (1260 +/- 168 mg for group 2 versus 1075 +/- 100 mg for group 1). After treatment with MK421, the weight of the contralateral kidney (1472 +/- 190 mg) was further increased. After 1 month of treatment with MK421 or vehicle, the unclipped left kidney was removed from all animals. The treated animals were then randomly divided into two groups: one in which treatment with MK421 was stopped (treated/untreated, n = 24; group 3) and a second in which the treatment was continued (treated/treated, n = 23; group 4). The ability of the rats to excrete a water load of 15 ml was then examined 12 hours after removal of the unclipped left kidney. In the two groups of treated rats, the urinary excretion of the water load was decreased and frequency of oliguria was increased as compared with controls and hypertensive untreated rats. Survival rates were affected by the treatment: 3 deaths occurred in the hypertensive untreated group 2, 10 in the treated/untreated group 3, and 12 in the treated/treated group 4. The majority of these deaths could be attributed to renal insufficiency.(ABSTRACT TRUNCATED AT 400 WORDS)     

The failure of furosemide-induced salt and water loss to convert benign to malignant hypertension in the rat.

The concept has been advanced that malignant hypertension is precipitated in the rat with renal hypertension by a sudden loss of sodium in the urine. In order to test this hypothesis modest degrees of hypertension were produced in Holtzman rats by the application of a silver clip to one renal artery, not touching the opposite kidney. When the systolic blood pressure reached a level between 160 and 180 mm Hg, loss of sodium and water was induced by the administration of furosemide, given either orally over a 7-day period, or by 3 intramuscular injections over a 24-hour period. Sodium and water balance studies, blood pressure determinations, histologic assessment of blood vessels in the nonclipped kidney, and measurement of activity of the juxtaglomerular apparatus were carried out in these 2 groups and appropriate control animals. It was found that in spite of a considerable natriuresis and diuresis in furosemide-treated animals, there was neither a significant increase in the blood pressure nor development of more severe vascular lesions in the nonclipped kidney than in the kidneys of control animals.     

Increased blood pressure during potassium depletion in normotensive men

Epidemiologic studies suggest an inverse relation between potassium intake and the prevalence of hypertension. To investigate the effect of dietary potassium restriction on blood pressure, we used a randomized crossover design to study 10 healthy, normotensive men randomly assigned to isocaloric diets (each lasting nine days) providing either low (10 mmol per day) or normal (90 mmol per day) amounts of potassium, while sodium intake was maintained at the subjects' usual levels (120 to 200 mmol per day). With the low-potassium diet, plasma potassium levels declined from 3.8 to 3.2 mmol per liter (P less than 0.001), but plasma sodium and chloride levels were unchanged. The average daily excretion of urinary sodium (+/- SEM) on the low-potassium diet was significantly lower than that with the normal-potassium diet (10 +/- 10 vs. 144 +/- 10 mmol; P less than 0.001). The mean arterial pressure did not change significantly during normal potassium intake, but it increased over the nine days of the low-potassium diet from 90.9 +/- 2.2 to 95.0 +/- 2.2 mm Hg (P less than 0.05). Both mean arterial (P less than 0.01) and diastolic (P less than 0.005) pressures were significantly higher after the low-potassium diet than after the normal-potassium diet. Potassium depletion suppressed plasma aldosterone levels but had no effect on plasma renin activity or on arginine vasopressin or catecholamine levels. A saline infusion further increased the mean arterial pressure in the potassium-depleted subjects but had no effect in the control group (P less than 0.05). We conclude that short-term potassium depletion increases blood pressure in healthy, normotensive men and permits further increases in blood pressure after saline loading. We found no evidence that the hypertensive effect of potassium depletion resulted from changes in either renal hemodynamics or circulating levels of vasoactive hormones.     

Serum lead levels in experimental hypertension

Serum lead (Pb) levels were determined by Atomic Absorption Spectrophotometry in Grollman renal hypertensive (RH), spontaneous hypertensive rats (SHR) and normotensive (NT) male rats of similar weight. Statistically significant (P less than 0.001) blood pressure elevations were obtained in the RH animals 195 +/- 12.0 mm Hg and the SHR animals measured 192 +/- 39 mm Hg compared with 136 +/- 4.79 mm Hg in the NT animals. Serum Pb values were elevated in both the RH 7.9 +/- 0.86 micrograms/dl, and NT 8.53 +/- 2.79 micrograms/dl animals whereas significantly lower (P less than 0.005) levels were measured in SHR 5.0 +/- 0.86 micrograms/dl animals. Blood hemoglobin and erythrocyte counts were normal and similar in all three groups of animals. These results show that serum Pb levels are not altered in RH rats compared with NT rats. The SHR animals had significantly lower levels of serum Pb, which probably reflect an indigeneous SHR condition.     

Hypotension and thirst in rats after isoproterenol treatment

Drinking induced in rats by systemic isoproterenol treatment is markedly attenuated after bilateral nephrectomy. The present experiments demonstrate that the hypotension produced by iso-proterenol treatment was more profound, and lasted much longer, in nephrectomized rats than in intact animals. When arterial blood pressure was partially elevated by central administration of angiotensin II or carbachol (Experiment 1) or by intraarterial infusion of epinephrine (Experiment 2), drinking behavior was restored in the nephrectomized animals and their water intakes approximated the amounts consumed by intact rats given isoproterenol. In general, an inverted U-shaped curve was found to define the relation between blood pressure and water intake in rats after isoproterenol treatment. Drinking was most probable when mean arterial blood pressures were in the range of 70–85 mm Hg, whereas rats were unlikely to drink when blood pressures were much below or above this range. These findings indicate that isoproterenol-induced thirst is not dependent on a renal dipsogen, and suggest instead that the hypersecretion of renin that occurs in intact rats is simply permissive of drinking behavior by modulating the hypotensive effects of the drug treatment.     

Renal hemodynamics and the renin-angiotensin-aldosterone system in normotensive subjects with hypertensive and normotensive parents

BACKGROUND AND METHODS. The kidney is important in blood-pressure regulation, but its role in the development of essential hypertension is still subject to debate. We compared renal hemodynamics, measured in terms of the clearance of para-aminohippuric acid and inulin, and the characteristics of the renin-angiotensin-aldosterone system in three groups of normotensive subjects at different degrees of risk for hypertension: 41 subjects with two normotensive parents, 52 with one normotensive and one hypertensive parent, and 61 with two hypertensive parents. The subjects ranged in age from 7 to 32 years. RESULTS. The mean renal blood flow was lower in the subjects with two hypertensive parents than in those with two normotensive parents (mean difference [+/- SE], 198 +/- 61 ml per minute per 1.73 m2 of body-surface area; P = 0.002). Moreover, both the filtration fraction and renal vascular resistance were higher in the subjects with two hypertensive parents (filtration fraction: mean difference, 3.0 +/- 1.1 percentage points; P = 0.006; renal vascular resistance: mean difference, 2.7 +/- 0.8 mm Hg per deciliter per minute per 1.73 m2; P = 0.006). The subjects with two hypertensive parents had lower plasma concentrations of renin (mean difference, 3.3 +/- 1.6 mU per liter; P = 0.03) and aldosterone (mean difference, 111 +/- 36 pmol per liter; P = 0.003) than those with two normotensive parents. The differences could not be explained by the small differences in blood pressure between the groups. The values in the subjects with one hypertensive and one normotensive parent fell between those for the other two groups. CONCLUSIONS. Renal vasoconstriction is increased and renin and aldosterone secretion is decreased in young persons at risk for hypertension. These findings support the hypothesis that alterations in renal hemodynamics occur at an early stage in the development of familial hypertension.     

The renal medulla and mechanisms of hypertension in the spontaneously hypertensive rat.

A significant number of offspring from brother-sister matings of NIH-Okamoto-Aoki spontaneously hypertensive rats (SHRs) were found to be normotensive at 20 weeks of age. Over 20% of the animals that were hypertensive at this age had mild-to-moderate unilateral hydronephrosis at the time of sacrifice. In over 90% of the rats that did not develop hypertension spontaneously, ligation of one ureter raised blood pressure above 150 mm Hg within 2 weeks. In those rats made hypertensive by obstructing one ureter and in those that developed hypertension with accompanying naturally occurring hydronephrosis, subcutaneous implants of fragmented renal medulla from unrelated normal rats decreased blood pressure to normotensive levels. In contrast, medullary implants had no significant effect in rats developing hypertension spontaneously without hydronephrosis. Renal inner medullary plasma flow was low in the obstructed kidneys of hydronephrotic hypertensive SHRs but was elevated in the kidneys of nonhydronephrotic hypertensive SHRs. The hypertension in hydronephrotic SHRs appears to be related to an impairment of the antihypertensive function of the renal medulla. Such an impairment of medullary antihypertensive function does not appear to play a significant role in the hypertension in SHRs without hydronephrosis.     

Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure

BACKGROUND: Inhibition of angiotensin-converting enzyme (ACE) reduces the risk of cardiovascular problems in patients with chronic renal failure. This effect may be due in part to a decrease in sympathetic nervous activity, but no direct evidence of such an action is available. METHODS: We studied muscle sympathetic-nerve activity in 14 patients with hypertension, chronic renal failure, and increased plasma renin activity before, during, and after administration of the ACE inhibitor enalapril. Ten other patients with similar clinical characteristics were studied before and during treatment with the calcium-channel blocker amlodipine. Normal subjects matched for age and weight were included in both studies. RESULTS: At base line, mean (+/-SD) muscle sympathetic-nerve activity was higher in the group of patients who received enalapril than in the control subjects (35+/-17 vs. 19+/-9 bursts per minute, P=0.004). The baroreflex curve, which reflects changes in muscle sympathetic-nerve activity caused by manipulations of blood pressure with sodium nitroprusside and phenylephrine, was shifted to the right in the patients, but baroreflex sensitivity was similar to that in the control subjects (-2.1+/-1.9 and -2.7+/-1.3 bursts per minute per mm Hg, respectively; P=0.36). A single dose of the sympatholytic drug clonidine caused a greater fall in blood pressure in the patients than in the control subjects. Treatment with enalapril normalized blood pressure and muscle sympathetic-nerve activity (at 23+/-10 bursts per minute) in the patients and shifted the baroreflex curve to the left, reflecting normal blood-pressure levels, without significantly changing sensitivity (-2.3+/-1.8 bursts per minute per mm Hg, P=0.96). In the patients who received amlodipine, treatment also lowered blood pressure but increased muscle sympathetic-nerve activity, from 41+/-19 to 56+/-14 bursts per minute (P=0.02). CONCLUSIONS: Increased sympathetic activity contributes to hypertension in patients with chronic renal disease. ACE inhibition controls hypertension and decreases sympathetic hyperactivity.     

Hemodynamic,renal, and hormonal responses to changes in dietary potassium in normotensive and hypertensive man: Long-term antihypertensive effect of potassium supplementation in essential hypertension

Summary The hemodynamic, hormonal, and renal responses to alterations in dietary potassium were studied in normotensive and hypertensive subjects. In a short-term study, nine normotensive and nine hypertensive young men received a normal diet and low potassium, high potassium, and high potassium/low sodium diets for 1 week, each. The long-term effect of potassium supplementation (normal diet plus 96 mmol KCl/d for 8 weeks) was evaluated in 17 patients with essential hypertension. Blood pressure did not change significantly during short-term alterations of potassium intake but decreased during long-term supplementation (from 152.2±3.5/99.6±1.9 mm Hg to 137.4±2.9/89.1±1.4 mm Hg). High dietary potassium induced a significant but transient natriuresis. Plasma potassium concentration was increased during long- but not during short-term high potassium intake. In contrast to plasma renin activity (PRA) and aldosterone, urinary kallikrein was consistently stimulated during long-term potassium supplementation. The plasma concentrations of adrenaline and noradrenaline were significantly higher in hypertensive than in normotensive subjects and were not markedly altered by the dietary changes. It is concluded that long- but not short-term potassium supplementation lowers blood pressure in patients with essential hypertension. The antihypertensive effect may be mediated by potassium-induced natriuresis, by a stimulation of Na-K-ATPase secondary to increased plasma potassium levels, and/or by a modulation of the renin-angiotensin-aldosterone, kallikrein-kinin, and sympathetic nervous systems.Abbreviations MAP mean arterial pressure - Na-K-ATPase sodium-potassium ATPase - PRA plasma renin activity The study was supported in part by the Ministerium für Wissenschaft und Forschung, Nordrhein-Westfalen (FA-92/14)     

Increased excretion of urinary N-acetyl-beta-glucosaminidase in essential hypertension and its decline with antihypertensive therapy

The urinary excretion of N-acetyl-beta-glucosaminidase (NAG) is increased in patients whose renal function is impaired by a variety of kidney diseases, and may provide an index of renal injury. To assess its role in essential hypertension, we measured urinary levels of NAG in 80 subjects with essential hypertension (and no evidence of renal disease) and 30 normal controls. NAG values were measured before therapy and after 3 and 12 months of treatment with diuretics. The mean urinary NAG value (+/- S.D.) for the normotensive subjects was 29 +/- 16 nmol per hour per milligram of urinary creatinine. The median value for the untreated hypertensive subjects was 53, and the mean was 65 +/- 61 (P less than 0.01). Systolic blood pressure was directly correlated with NAG levels, whereas diastolic pressure, age, sex, and race were not. Eighty patients followed for one year attained their ultimate blood-pressure reduction within three months (from a mean of 158/103 mm Hg to one of 138/91 mm Hg; P less than 0.001), whereas the urinary NAG level had not declined significantly at three months (from 60 +/- 43 to 54 +/- 54) but had changed significantly at one year (to 45 +/- 28; P less than 0.01 as compared with the initial value). These data suggest that NAG is frequently elevated in patients with high blood pressure even though there is no other evidence of renal damage, and that it can be reduced by successful antihypertensive therapy.     

Depolarization pattern of ventricular epicardium in two-kidney one-clip hypertensive rats

The present study is the first attempt to examine the effect of left ventricular hypertrophy (LVH) on the excitation pattern of the ventricular epicardium in experimental hypertensive rats. The left renal artery was clipped in Wistar rats (n = 8; 6-8 months old; weight, 174-295 g) to produce two-kidney one-clip (2K1C) hypertension. After 4 weeks, blood pressure was measured, and epicardial potential mapping was performed under sinus rhythm from 64 unipolar electrodes regularly distributed over the ventricular epicardium. Systolic blood pressure was approximately 40% higher in the rats with a clipped renal artery (162 +/- 14 mmHg, mean +/- s.d.) than in the normotensive rats (115 +/- 3 mmHg). LVH (approximately 23% increase in the ratio of the left ventricular weight to the body weight, P < 0.05) was observed in the 2K1C hypertensive rats. The depolarization pattern of the ventricular epicardium in the normotensive rats was similar to that in the rats with 2K1C hypertensive LVH. The duration of ventricular epicardial activation was shown to increase (approximately 35%, P < 0.05) in the hypertensive rats as compared to the normotensive animals. This study provides an explanation for alterations of the body surface potential distribution in hypertensive patients with LVH.     

Afferent arteriolar diameter in DOCA-salt and two-kidney one-clip hypertensive rats

The afferent arteriolar diameter (dAA) was investigated during development of hypertensive renal disease in normal and uninephrectomized control rats, in chronic DOCA-salt (DOCA), post-DOCA (p-DOCA), and chronic two-kidney one-clip (2K-1C) hypertensive rats, and in post-two-kidney one-clip (p-2K-1C) normotensive rats. dAA was measured by the microsphere method. Nephron loss was present in the kidneys exposed to elevate blood pressure. The dAA was reduced from 19.9 to 17.2 micron in the DOCA group (P less than 0.001) and from 19.1 to 16.3 micron in the nonclipped kidneys in the 2K-1C group (P less than 0.001). The dAA increased from 19.9 to 20.7 micron in the p-DOCA group. Afferent arteriolar dilatation from 19.1 to 21.0 micron (P less than 0.001) was present about 50 days after clipping in the 2K-1C group; in the clipped kidneys the dAA returned to normal (18.9 micron) after declipping. No relation between the dAA and plasma renin concentration was observed. In all models dAA was the same in three cortical layers of equal thickness. Accordingly, chronic renal DOCA-salt hypertension constricts the afferent arteriole with angiotensin-independent mechanisms. Autoregulatory dilatation of the afferent arteriole seems to be maintained for at least 50 days. When the hypertension is moderate, dAA in damaged kidneys may be dilated.     

Preservation of renal structure and function in the rat remnant kidney model of chronic renal failure by enalapril treatment

The remnant kidney model of chronic renal failure was established in rats subject to subtotal (1 7/8) nephrectomy and the evolution of renal injury studied over a period of 6 wk. One wk after subtotal nephrectomy, rats had a mean conscious systolic blood pressure of 158 +/- 5 mm Hg and serum creatinine of 128 +/- 9 mumol/l. Both systolic blood pressure and serum creatinine rose over the next 5 wk in concert with progressive glomerulosclerosis and proteinuria. Enalapril, an angiotensin converting enzyme inhibitor, was administered (5 mg/kg/day) to rats (n = 11) from 1 wk after subtotal nephrectomy. Enalapril lowered systolic blood pressure over the treatment period. Systolic blood pressure was 122 +/- 5 mm Hg compared with 176 +/- 7 mm Hg in untreated rats (p less than 0.001) at 6 wk. Serum creatinine 6 wk after subtotal nephrectomy was 110 +/- 9 mumol/l with enalapril treatment, compared with 159 +/- 21 mumol/l (p less than 0.025) in control animals. Enalapril treated rats had lower urinary protein excretion than controls (15 +/- 3 mg/24 hr vs 85 +/- 22 mg/24 hr, p less than 0.0001) at 6 weeks. Glomerulosclerosis, assessed by blinded histological score, was also reduced in the enalapril treated group (1.79 +/- 0.08 vs 2.36 +/- 0.16, p less than 0.01). Enalapril treatment was associated with a reduction in filtration fraction (51Cr-EDTA/125I-hippurate clearance). At 6 wk, filtration fraction was 0.30 +/- 0.03 in enalapril treated and 0.48 +/- 0.03 in control rats (p less than 0.001). Enalapril treatment in the subtotal nephrectomy model of renal failure preserved renal structure and function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ingestion of hypertonic NaCl vs. palatable drinks by sodium-depleted rats

This work investigated whether the preference for NaCl solution is shifted to more palatable solutions in the adult male sodium-depleted rat (n=6-10 per group). Animals had daily access to three bottles, one containing water, another 1.8% NaCl (300 mM), and a third containing 0.9% NaCl (150 mM), Gatorade (orange--OG or grape flavored--GG), orange juice (sweetened or unsweetened, from concentrate), or 10% sucrose (no sodium). Sodium content in Gatorade and orange juice ranged from 7 to 14 mEq/l. Daily intakes were recorded for at least 5 days prior to sodium depletion. Then, the animals were depleted of sodium (diuretic plus sodium-deficient diet and water for 24 h). Then, the other two bottles were returned to the animals and the intakes were recorded for 120 min (sodium preference test, SPT). Daily intake from the third bottle (except for unsweetened orange juice) at least doubled the daily 1.8% NaCl intake. The average 1.8% NaCl intake (13+/-2 ml) in the SPT was higher than the intake of 10% sucrose (6+/-1 ml) or of any other solution (less than 6 ml). The intakes of 1.8% NaCl and 0.9% NaCl (10+/-3 ml) were similar during the SPT. The animals also preferred 0.9% NaCl (27+/-1 ml) to OG (3+/-1 ml) in the absence of 1.8% NaCl in the SPT. Therefore, the preference for sodium in sodium-depleted rats also applies when palatable and nutritive solutions are simultaneously available.     

The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis. Dutch Renal Artery Stenosis Intervention Cooperative Study Group

BACKGROUND: Patients with hypertension and renal-artery stenosis are often treated with percutaneous transluminal renal angioplasty. However, the long-term effects of this procedure on blood pressure are not well understood. METHODS: We randomly assigned 106 patients with hypertension who had atherosclerotic renal-artery stenosis (defined as a decrease in luminal diameter of 50 percent or more) and a serum creatinine concentration of 2.3 mg per deciliter (200 micromol per liter) or less to undergo percutaneous transluminal renal angioplasty or to receive drug therapy. To be included, patients also had to have a diastolic blood pressure of 95 mm Hg or higher despite treatment with two antihypertensive drugs or an increase of at least 0.2 mg per deciliter (20 micromol per liter) in the serum creatinine concentration during treatment with an angiotensin-converting-enzyme inhibitor. Blood pressure, doses of antihypertensive drugs, and renal function were assessed at 3 and 12 months, and patency of the renal artery was assessed at 12 months. RESULTS: At base line, the mean (+/-SD) systolic and diastolic blood pressures were 179+/-25 and 104+/-10 mm Hg, respectively, in the angioplasty group and 180+/-23 and 103+/-8 mm Hg, respectively, in the drug-therapy group. At three months, the blood pressures were similar in the two groups (169+/-28 and 99+/-12 mm Hg, respectively, in the 56 patients in the angioplasty group and 176+/-31 and 101+/-14 mm Hg, respectively, in the 50 patients in the drug-therapy group; P=0.25 for the comparison of systolic pressure and P=0.36 for the comparison of diastolic pressure between the two groups); at the time, patients in the angioplasty group were taking 2.1+/-1.3 defined daily doses of medication and those in the drug-therapy group were taking 3.2+/-1.5 daily doses (P<0.001). In the drug-therapy group, 22 patients underwent balloon angioplasty after three months because of persistent hypertension despite treatment with three or more drugs or because of a deterioration in renal function. According to intention-to-treat analysis, at 12 months, there were no significant differences between the angioplasty and drug-therapy groups in systolic and diastolic blood pressures, daily drug doses, or renal function. CONCLUSIONS: In the treatment of patients with hypertension and renal-artery stenosis, angioplasty has little advantage over antihypertensive-drug therapy.     

Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group

BACKGROUND: The effect of dietary composition on blood pressure is a subject of public health importance. We studied the effect of different levels of dietary sodium, in conjunction with the Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in vegetables, fruits, and low-fat dairy products, in persons with and in those without hypertension. METHODS: A total of 412 participants were randomly assigned to eat either a control diet typical of intake in the United States or the DASH diet. Within the assigned diet, participants ate foods with high, intermediate, and low levels of sodium for 30 consecutive days each, in random order. RESULTS: Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg (P<0.001) during the control diet and by 1.3 mm Hg (P=0.03) during the DASH diet. Reducing the sodium intake from the intermediate to the low level caused additional reductions of 4.6 mm Hg during the control diet (P<0.001) and 1.7 mm Hg during the DASH diet (P<0.01). The effects of sodium were observed in participants with and in those without hypertension, blacks and those of other races, and women and men. The DASH diet was associated with a significantly lower systolic blood pressure at each sodium level; and the difference was greater with high sodium levels than with low ones. As compared with the control diet with a high sodium level, the DASH diet with a low sodium level led to a mean systolic blood pressure that was 7.1 mm Hg lower in participants without hypertension, and 11.5 mm Hg lower in participants with hypertension. CONCLUSIONS: The reduction of sodium intake to levels below the current recommendation of 100 mmol per day and the DASH diet both lower blood pressure substantially, with greater effects in combination than singly. Long-term health benefits will depend on the ability of people to make long-lasting dietary changes and the increased availability of lower-sodium foods.     

Beschleunigte Natriurese und Diurese beim Hochdruck: Folge einer Resorptionshemmung in der Henleschen Schleife

Summary Exaggerated natriuresis and diuresis in chronic hypertension: Result of impaired fluid reabsorption in the loop of Henle.Micropuncture studies were performed in normotensive and chronically hypertensive rats (unilateral renal artery stenosis). Excretory and tubular function of the untouched kidney exposed to the high blood pressure (185 mm Hg) was investigated before and after i.v. 2.5% sodium chloride loading (0.1 ml/min) and compared to that of normotensive rats (98 mm Hg). The onset of diuresis and natriuresis was more rapid in the hypertensive rats than in the control group. Fractional sodium excretion of the hypertensive rats rose to 11% of the filtered load, while it reached only 3% in the controls. Total GFR and superficial single nephron GFR were elevated in both groups, but the increase in filtration rate occured earlier in the hypertensive group. Fractional sodium and water reabsorption in the proximal tubule decreased in both groups to the same extent. In the hypertensive rats, fractional water reabsorption along the loop of Henle was less than half of normal. The reduced fractional reabsorption in Henle's loop was already present in the control period and is thought to be the result of an increased medullary blood flow caused by the high blood pressure. Early distal TF/P-Inulin ratio declined from 2.8 to 1.9 in the hypertensive group and from 4.7 to 2.45 in the control group. In the normotensive group the reduced proximal reabsorption was partly compensated by an increased fractional reabsorption in distal tubules and collecting ducts. In contrast, there was a marked reduction of fractional water reabsorption in distal tubules of the hypertensive group. The combined inhibition of fractional reabsorption in the proximal tubule, in Henle's loop and in the distal tubule leads to the exaggerated natriuresis and diuresis in the hypertensive rats.

     

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.     

Foetal placental blood flow in the lamb

1. Fifteen sheep foetuses of 1.5-5.2 kg body weight were prepared with indwelling arterial and venous catheters for experimentation one to six days later.2. Unanaesthetized foetuses were found to have mean arterial and central venous blood pressures of 40 +/- 1.5 (S.E. of mean) and 2.0 +/- 0.3 (S.E. of mean) mm Hg respectively, compared to intra-uterine pressure. Intra-uterine pressure was 16 +/- 0.8 (S.E. of mean) mm Hg with respect to atmospheric pressure at mid-uterine level.3. Mean placental blood flow of the foetuses was 199 +/- 20 (S.E. of mean) ml./(min.kg body wt.). Mean cardiac output in eleven of the foetuses was 658 +/- 102 (S.E. of mean) ml./(min.kg).4. Mean foetal and maternal colloid osmotic pressures were 17.5 +/- 0.7 (S.E. of mean) and 20.5 +/- 0.6 (S.E. of mean) mm Hg respectively at 38 degrees C.5. Intravenous infusions into six ewes of 1.8 mole of mannitol and 0.4 mole of NaCl resulted in significant increases in foetal plasma osmolarity, sodium, potassium, and haemoglobin concentrations, without detectable transfer of mannitol to the foetal circulation.6. In the sheep placenta there is osmotic and hydrostatic equilibration of water. As a consequence, there should be an interaction between foetal placental blood flow and foetal water exchange with the maternal circulation. It was concluded that this interaction tends to stabilize foetal placental blood flow.     

Osmotic and hypovolemic thirst in spontaneously hypertensive rats

Osmotic- and hypovolemic-induced water intake as well as urinary excretion of sodium and other solutes were compared in spontaneously hypertensive (SHR) and normotensive Wistar (NWR) rats. No significant differences were found between SHR and NWR in water intake and urinary excretion under conditions of euhydration and in response to 24 hr water deprivation. Administration of osmotic load (0.5 ml.100 g-1 body weight of 10% NaCl IV) elicited: (1) higher intake of water (by 1.77 +/- 0.60 ml.100 g-1 body weight), (2) lower urinary excretion of sodium and other solutes, and (3) greater retention of fluid in SHR than in NWR. Reduction of blood volume by amount equivalent to 1.8% of body weight decreased arterial blood pressure by 31.9 +/- 3.5 and 10.8 +/- 1.7 mmHg in SHR and NWR, respectively. In spite of significantly greater hypotension, bleeding elicited in SHR smaller elevation of water intake than in NWR (1.39 +/- 0.25 vs. 2.14 +/- 0.49 ml.100 g-1 body weight). The data provide evidence for existence of significant differences in the control of body fluid balance between SHR and NWR. It is suggested that hyperdipsia elicited by administration of the hyperosmotic load in SHR does not result from primary hyperresponsiveness of the thirst system to osmotic/sodium stimulation but is rather secondary to osmotic load retention.