The effect of isoprenaline infusion on renal renin and angiotensinogen gene expression in the anaesthetised rat

In this study, we investigated the ability of acute infusions of isoprenaline to alter renin and angiotensinogen gene expression in the kidney of rats anaesthetised with chloralose-urethane. Groups of rats received I.V. infusions of either saline or the beta-adrenoceptor agonist isoprenaline at 400 ng x kg(-1) x min(-1) for 4 h. The isoprenaline infusion caused a sustained decrease in mean blood pressure of approximately 20 mmHg (P < 0.01), an increase in heart rate of 50 beats x min(-1) (P < 0.01) and reductions in urine flow and sodium excretion of 80-90 % (both P < 0.01). Renal blood flow and glomerular filtration rate were transiently reduced by 21 % (P < 0.01) and 61 % (P < 0.001), respectively, in the first hour, recovering to baseline levels after 4 h of infusion. At the end of the study, plasma renin activity was raised approximately 6-fold (P < 0.01) while renal renin and angiotensinogen mRNA levels were 1.8- and 1.5-fold higher (both P < 0.05) compared to the control group (saline infusion). The isoprenaline-induced renin secretion could have been mediated via the activation of beta-adrenoceptors resulting in the exocytosis of renin-containing granules, with a smaller contribution being due to reduced renal haemodynamics. The increase in renal renin gene expression in response to isoprenaline was probably due primarily to the intracellular signalling processes acting directly on nuclear mechanisms. Similarly, the increased renal angiotensinogen gene expression most probably reflected a direct action of the isoprenaline. These findings provide evidence that catecholamines are involved in mechanisms that rapidly alter the expression of the genes of the renin-angiotensin system within the kidney.     

Renal and haemodynamic effects of nitric oxide blockade in a Wistar assay rat during high pressure cross-circulation of an isolated denervated kidney

Blockade of NO synthesis with N-ω-nitro-L-arginine (L-NNA) inhibits the vasodepressor response seen in intact Wistar assay rats in which isolated kidneys perfused via an extracorporeal circuit are perfused at high pressure. This study explores the renal and haemodynamic changes associated with this inhibition. Isolated kidneys (IK) were perfused at high pressure (175 mmHg) by a pump in series with intact Wistar assay rats in which blood pressure (BP), haemodynamics and renal function were studied. Nitric oxide (NO) synthesis was blocked by L-NNA (2.5 mg kg^-1) in 13 experiments (175NO) while 14 control experiments (175C) were performed. IK was perfused at 90 mmHg in seven experiments (90C). The BP drop in the 175C assay rat was blocked by L-NNA in 175NO (P < 0.01). However, when the blockade was reversed with L-arginine infusion (20 mg kg ^J min“¹) BP declined also in 175NO. Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) fell dramatically after L-NNA in both the assay rat and in IK despite a high perfusion pressure. The marked increase in filtration fraction (FF) after L-NNA suggests a dominating postglomerular vasoconstriction. The natriuretic response in IK to 175 mmHg was also markedly blunted by L-NNA. We conclude that NO blockade inhibits the renomedullary depressor mechanism probably by restricting renal blood flow, and also blunts the pressure induced natriuretic response as a result of a reduced sodium filtration. Finally, the autoregulation of whole kidney blood flow seems to be more efficient although set at a higher level of vasoconstriction.     

Renal effects of furosemide in glycerol induced acute renal failure of the rat

Summary The renal effects of furosemide in acute renal failure of the rat were studied using clearance and micropuncture techniques. Acute renal failure was induced by an intramuscular injection of 50% glycerol (10 ml/kg). Functional impairement of the glycerol treated animals consisted of a decrease in urinary sodium excretion, renal blood flow, total kidney GFR and effective filtration pressure of superficial nephrons. Effective filtration pressure was calculated from proximal free flow and stop flow pressure measurements.In contrast to control animals furosemide did not increase urine volume during acute renal failure due to a marked fall in GFR. Renal blood flow, as measured by an electromagnetic flowmeter, also decreased after furosemide in glycerol treated rats and increased in control animals. Furosemide reduced effective filtration pressure during acute renal failure to almost zero, whereas in control animals effective filtration pressure virtually remained constant.Supported by Deutsche Forschungsgemeinschaft.     

Chronic kidney disease: cardiac and renal angiotensin-converting enzyme (ACE) 2 expression in rats after subtotal nephrectomy and the effect of ACE inhibition

Renin-angiotensin system blockade slows but does not prevent the cardiovascular complications of chronic kidney disease (CKD). Angiotensin-converting enzyme (ACE) 2 is differentially regulated in acute kidney injury, with increased cardiac ACE2 but decreased kidney ACE2 levels. This study investigated the effect of long-term ACE inhibition on cardiac and renal ACE2 in rats with CKD induced by subtotal nephrectomy (STNx). Sprague-Dawley rats had sham (control) or STNx surgery. Control rats received vehicle (n = 9) and STNx rats ramipril (1 mg kg(-1) day(-1); n = 10) or vehicle (n = 10) for 28 days. Subtotal nephrectomy resulted in impaired creatinine clearance (P < 0.05), proteinuria (P < 0.05), renal fibrosis (P < 0.05) and reduced renal cortical ACE2 mRNA (P < 0.05) and activity (P < 0.05). In rats with CKD, ramipril improved creatinine clearance (P < 0.05) and was associated with an increase in cortical but not medullary ACE2 activity (P < 0.05). Compared with control rats, STNx rats were hypertensive (P < 0.01), with increased left ventricular end-diastolic pressure (LVEDP; P < 0.01), left ventricular hypertrophy (LVH; P < 0.05) and interstitial (P < 0.05) and perivascular fibrosis (P < 0.01). In rats with CKD, ramipril decreased blood pressure (P < 0.001) and reduced LVEDP (P < 0.01), LVH (P < 0.01) and perivascular fibrosis (P < 0.05) but did not significantly reduce interstitial fibrosis. There was no change in cardiac ACE2 in rats with CKD compared with control rats. In rats with CKD, ACE inhibition had major benefits to reduce blood pressure and cardiac hypertrophy and to improve creatinine clearance, but did not significantly impact on cardiac ACE2, cardiac interstitial fibrosis, renal fibrosis or proteinuria. Thus, in rats with CKD, renal ACE2 deficiency and lack of activation of cardiac ACE2 may contribute to the progression of cardiac and renal tissue injury. As long-term ACE inhibition only partly ameliorated the adverse cardio-renal effects of CKD, adjunctive therapies that lead to further increases in ACE2 activity may be needed to combat the cardio-renal complications of CKD.     

血清同型半胱氨酸水平变化与原发性高血压肾损伤的关系

目的:探讨血清同型半胱氨酸(Hcy)水平与原发性高血压肾损伤的关系。方法:131例原发性高血压患者根据尿微量白蛋白/肌酐比值(UmAlb/Cr)分为尿蛋白阴性组、微量蛋白尿组和大量蛋白尿组,分别测定Hcy、UmAlb/Cr、胱抑素C(Cys C)和肾小球滤过率(GFR)等指标,并比较各指标与健康对照人群的差异,分析高血压肾损伤患者Hcy水平与肾功能指标UmAlb/Cr、Cys C和GFR的相关性。结果:与健康对照组和尿蛋白阴性组比较,微量蛋白尿组和大量蛋白尿组Hcy及UmAlb/Cr、Cys C明显升高,GFR明显降低,差异均有统计学意义(P0.05,P0.01),尤以大量蛋白尿组更显著(P0.01)。相关性分析显示,Hcy与UmAlb/Cr、Cys C呈显著正相关(r=0.442、0.325,P均0.01),Hcy与GFR呈显著负相关(r=-0.286,P0.01)。结论:Hcy与高血压肾损伤相关,可以作为高血压肾损伤的观察指标之一。     

Adenosine response of the rat kidney after saline loading,sodium restriction and hemorrhagia

Experiments were performed on three groups of rats. The first group consisted of sodium loaded (SL) rats (high sodium diet, 10 meq Na/day, the second group consisted of sodium restricted (SR) rats (low sodium diet, 0.7 meq Na/day) and the third group consisted of hemorrhagic rats (HR), which were bled with 1-1,5% of the body weight. Blood pressure, glomerular filtration rate (GFR) and sodium excretion were measured. In some animals renal blood flow (RBF) was recorded with an electromagnetic flow meter. Adenosine was injected or infused into the thoracic aorta. Bolus injection of 10 nmoles adenosine resulted in a rapid and marked decrease of RBF (40%) in SR rats whereas in SL rats only a very small decrease of RBF (2%) was observed. Continuous infusion of adenosine (10(-7) moles/min) decreased GFR by 54% in SR rats and by 33% in HR rats, whereas GFR in SL rats did not change significantly. 5'-AMP decreased GFR in SR rats by 18% and in HR rats by 32%. Adenosine and 5'-AMP caused a slight fall in the systemic blood pressure, but this decrease could not account for the decrease of GFR. The sensitivity of kidney vasculature to adenosine parallelled high plasma renin activity (162 ng ang/ml-h in SR and 76 ng ang/ml-h in HR), elevated renal vascular resistance and low GFR. Simultaneous infusion of angiotensin (Hypertensin), 250 ng/min, in SL rats resulted in an increase of sensivity to adenosine infusion: GFR decreased by 21%. Our experiments demonstrated that a marked renal vasoconstriction caused by adenosine only occurs in rats in which renin-angiotensin system was stimulated.     

Hydrostatic and oncotic pressures in the interstitium of dehydrated and volume expanded rats

The pressures in the renal interstitial space seem to have important influence on the setting of the sensitivity of the tubuloglomerular feedback that controls the glomerular filtration rate (GFR), and on the rate of proximal tubular fluid reabsorption. Measurements were made of interstitial pressure conditions, GFR, renal plasma flow (RPF), urinary excretion of sodium and potassium, and plasma renin activities in dehydrated animals and normopenic controls, before and after saline volume expansion (5% of body weight and hour). Colloid osmotic pressure, estimated from the protein concentration in renal hilar lymph, was 7.5 mmHg in the dehydrated animals (controls 2.8 mmHg) and decreased to 3.1 (controls 1.7 mmHg) after volume expansion. The lymph flow rate was increased in both groups of animals after volume expansion. Interstitial hydrostatic pressure, measured in the subcapsular space, was 2–3 mmHg in dehydrated and control animals and increased to 3–4 mmHg after volume expansion. In dehydrated rats GFR and RPF was reduced to 60% of the control values, but after volume expansion they regained control values. After volume expansion, urinary excretion of fluid and electrolytes increased more in controls than in dehydrated rats. Plasma renin activity was dereased in both groups of rats after volume expansion. Thus, in dehydrated animals there was a high colloid osmotic pressure and a low hydrostatic pressure in the renal interstitium, while after volume expansion the oncotic pressure fell and the hydrostatic pressure rose. The effect of volume expansion was found to be dependent on the preceding volume balance situation in the animal.     

Renal, cardiovascular and endocrine responses of fetal sheep at 0.8 of gestation to an infusion of amino acids

Amino acid infusions increase renal blood flow (RBF) and glomerular filtration rate (GFR) and stimulate tubular reabsorption in adults. To characterize the effects of amino acids on fetal renal haemodynamics, tubular sodium reabsorption, acid-base homeostasis and plasma renin levels, 11 chronically catheterized fetal sheep aged 121 ± 1 days (term ∼150 days) were infused i.v for 4 h with alanine, glycine, proline and serine (0.1, 0.1, 0.06 and 0.06 mmol min⁻¹, respectively) in 0.15 m saline at 0.165 ml min⁻¹. Eight control fetuses were given saline. During amino acid infusion, plasma amino acid levels increased up to 20-fold (   P < 0.005  ). GFR increased by 50 ± 8 % (   P < 0.001  ); there was only a small transient increase in RBF. Proximal fractional sodium reabsorption fell from 74.6 ± 2.9 to 55.5 ± 5.4 % (   P < 0.005  ). Distal sodium delivery increased, but a smaller percentage of this distal sodium load was reabsorbed (   P < 0.005  ). Thus fractional sodium reabsorption fell from 95.5 ± 0.9 to 81.4 ± 2.0 % (   P < 0.005  ). There was a large diuresis, natriuresis, kaliuresis and increase in osmolar excretion (   P < 0.005  ). Plasma sodium and chloride concentrations fell (   P < 0.005  ). Plasma osmolality did not change. Plasma renin levels fell (   P < 0.05  ), cortisol levels increased (   P < 0.05  ), and there was a compensated metabolic acidosis. Thus the fetal sheep kidney demonstrated a remarkable functional capacity to respond to amino acid infusion. The increase in filtration fraction and the lack of an increase in RBF suggest that efferent arteriolar vasoconstriction occurred, a very different response from the renal vasodilatation seen in adult animals.     

Impaired sodium excretion, decreased glomerular filtration rate and elevated blood pressure in endothelin receptor type B deficient rats

The renal endothelin (ET) system, particularly the ET type B receptor, has been implicated in the regulation of sodium excretion and glomerular filtration rate (GFR). We analyzed kidney morphology and function in a rat strain characterized by complete absence of a functional ETB receptor. Due to Hirschsprung's disease limiting lifetime in these rats, studies were performed in 23-day-old rats. Kidney size and morphology (glomerular and interstitial matrix content, glomerular size and cell density and intrarenal vascular morphology) were normal in ETB-deficient rats. There were also no evidence of altered kidney cell cycle regulation in these rats. GFR was significantly lower, by 72% (P<0.001), in homozygous ETB-deficient rats than in wild-type rats. Fractional sodium excretion was likewise markedly reduced by 84% in homozygous ETB-deficient rats (P<0.001 versus wild-type rats). Treatment with the specific epithelial sodium channel blocker amiloride led to a much higher increase in fractional sodium excretion in ETB-deficient rats (934.2+/-73% in ETB-deficient rats versus 297+/-20% in wild-type rats, expressed as percentage of corresponding placebo treated control; P<0.001). Mean arterial blood pressure was elevated by 7.9 mmHg in homozygous ETB-deficient rats (P<0.05 versus wild-type rats). Our study demonstrates that ETB-deficiency causes early onset kidney dysfunction characterized by a markedly reduced sodium excretion, decreased GFR, and slightly elevated blood pressure. The complete absence of the ETB receptor causes in the kidney--in contrast to the colon--a functional rather than a developmental, neural crest cell dependent disease, since kidney morphology was normal in ETB-deficient rats. The much higher increase in the fractional sodium excretion in ETB-deficient rats after pharmacological blockade of the epithelial sodium channel indicates that the decreased fractional sodium excretion in ETB-deficient rats is most probably due to a lack of the inhibitory property of the ETB receptor on the epithelial sodium channel activity.     

Effect of isotonic volume expansion on glomerular filtration rate and renal hemodynamics in the developing rat kidney

Young rats (20–24 days) and adult rats (4–5 days) were studied during hydropenia and volume expansion with regard to glomerular filtration rate (GFR) and the determinants of GFR. During hydropenia, GFR and renal blood flow (RBF) were significantly lower in younger than in adult rats both in absolute terms and when related to bodyweight. Equivalent degrees of volume expansion (6% of b. wt.) resulted in a much more pronounced increase in GFR and RBF in younger than in older rats. This suggests that the high renal vascular resistance in hydropenic young rats is primarily due to vasoconstriction. The relationship between the filtration rate of superficial nephrons and the total GFR was the same in hydropenic and volume expanded rats in both age groups. The tubular stop flow pressure, the calculated hydrostatic glomerular capillary pressure and ultrafiltration pressure in the afferent part of the glomerular capillaries was slightly lower in hydropenic young rats than in hydropenic adult rats. The pressures did not rise after volume expansion. It is concluded that the marked increase in GFR in volume expanded young rats is mainly due to increased renal plasma flow.     

The mechanism of acute renal ischaemia caused by adrenalectomy in the rat.

1. The acute reduction of renal blood flow following adrenalectomy in the rat, which had previously been shown to be associated with sequestration of blood volume in the splanchnic area, was further investigated. An attempt was made to define the role of the renal sympathetic nerves in causing the blood flow change. 2. The systemic and renal intra-arterial administration of phenoxybenzamine, isoprenaline and propranolol and denervation of the renal pedicle failed to re-establish normal renal function. 3. Infusion of P113 (sarcosyl1 alanine8), an angiotensin blocker, failed to improve renal function. 4. In contrast, volume replacement with high-molecular weight PVP caused a prompt increase of RPF and GFR without altering arterial pressure and central venous pressure. 5. Angiographic studies demonstrated that the calibre of the aorta of adrenalectomized rats was significantly smaller than that of the sham operated and increased after the administration of this plasma volume expander. 6. It was concluded that after adrenalectomy the major arteries readjusted their calibre to the reduced volume of blood in the arterial tree with maintenance of a constant pressure/volume relationship. Their contracted state in the case of the kidney then led to flow reduction.     

Nitric oxide and the role of blood pressure variability to the kidney.

Blood pressure variability is buffered by at least two mechanisms: the arterial baroreceptor reflex and nitric oxide (NO). Only recently is the importance of blood pressure variations on cardiovascular control being investigated. Here we report of a study performed in conscious dogs, in which renovascular hypertension was induced. Reduction of renal arterial pressure (RAP) to 85 mmHg for 24 h elicited profound hypertension by 60 mmHg (vs. control: 110 +/- 3 mmHg; P < 0.01). This was accompanied by reduced volume and sodium excretion (-48% of control, P < 0.01 and -80% of control, P < 0.01, respectively) and augmented renin release by more than two-fold (P < 0.01). This intervention was compared with a protocol in which RAP was reduced to the same mean value, however, RAP oscillated by +/-10 mmHg at 0.1 Hz. This manoeuvre led to a transient increase in NO3 excretion in urine (P < 0.01), blunted antidiuresis (-14% of control) as well as antinatriuresis (-40% of control) and attenuated the increased renin release by 30% (P < 0.05). In consequence, the magnitude of blood pressure increase was only half as high as that observed during static reduction of RAP (P < 0.01). It is concluded that blood pressure oscillations to the kidney have a profound influence on water and electrolyte balance and on renin release, which alleviates the onset of Goldblatt hypertension.     

Factors affecting the maturation of glomerular filtration rate and renal plasma flow in the new-born dog

1. The maturation of glomerular filtration rate was studied by comparison of thirty-six new-born mongrel dogs aged 1-35 days with six adult dogs.2. Under mannitol diuresis, glomerular filtration rate (GFR) rose from 0.16 ml. min(-1).g kidney(-1) at 1 day of age to 0.34 ml. min(-1).g kidney(-1) at 1 month of age. Adult GFR averaged 0.68 ml. min(-1).g(-1). There was good correlation of GFR with arterial blood pressure (r = 0.76, P < 0.001). Part of the statistical correlation of GFR with blood pressure was found to be independent of the relationship between blood pressure and age.3. Acute increases or decreases in blood pressure resulted in parallel changes in GFR in the puppies. There was no change of GFR with change of blood pressure in adult dogs. Carotid artery clamping, independent of blood pressure changes, produced increased renal vascular resistance and decreased GFR in the pups.4. Renal plasma flow (RPF) increased from 0.70 ml. min(-1).g(-1) at 1 day of age to 1.80 ml. min(-1).g(-1) at 1 month and showed good correlation with blood pressure (r = 0.67, P < 0.001). Filtration fraction (GFR/RPF) and renal vascular resistance did not vary with age in the pup and were the same as those for the adult.5. These results support the hypothesis that maturation of GFR and RPF are closely related to maturation of arterial blood pressure in the mongrel dog. The factors other than blood pressure which also affect renal maturation in the dog still need to be more clearly defined.     

Tubuloglomerular feedback in hypertensive rats of the Milan strain

In rats of the Milan hypertensive strain (MHS) the disease can be transplanted with the kidney to rats of the Milan normotensive strain (MNS). It has been found that GFR, salt and volume regulation differ between MHS and MNS rats. Tubuloglomerular feedback control mechanism (TGF) is important for body volume regulation and we therefore wanted to study the TGF control in MHS and MNS rats. Whole kidney and micropuncture experiments were done before and during saline volume expansion (5% of body weight). In an initial series of experiments measurements were made of total kidney GFR, urine excretion rate of sodium and potassium and subcapsular interstitial hydrostatic pressure (psc); interstitial oncotic pressure (pi int) was estimated from hilar lymph protein concentration. In a second series, proximal tubular stop-flow pressure (psf) was determined upstream from a wax block while the distal nephron was being perfused with Ringer solution at a flow rate varying from 0 to 40 nl X min-1. In this way the maximal drop in stop-flow pressure (delta psf) and also the turning point (TP), the tubular flow rate at which 50% of this response was achieved, could be determined after saline volume expansion and after 2 h of complete ureteral occlusion. The results showed that GFR was similar in MHS and MNS rats in the control situation, but that during volume expansion it was significantly lower in the MHS group. Interstitial psc and pi int and net interstitial pressure (psc - pi int) were similar in MHS and MNS rats both under control conditions and during volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differences in the renal dopaminergic system activity between Wistar rats from two suppliers

AIM: Dopamine of renal origin reduces tubular sodium reabsorption and controls blood pressure. The present study evaluated renal dopaminergic activity and its response to uninephrectomy in Wistar Han rats from two suppliers, Harlan (W-H) and Charles River (W-CR). RESULTS: After uninephrectomy, the fractional excretion of sodium (FENa+) increased in both W-CR and W-H rats (W-CR: from 0.17 +/- 0.01 to 0.27 +/- 0.02%; W-H: from 0.39 +/- 0.04 to 0.54 +/- 0.04%, P < 0.05); however, in W-CR rats the FENa+ was lower than in W-H rats in both Sham and uninephrectomized (Unx) animals (P < 0.05). Systolic blood pressure in Unx W-CR rats was higher than in Unx W-H animals (131 +/- 3 vs. 122 +/- 2 mmHg, P < 0.05). Uninephrectomy was accompanied in W-H rats by increases in urinary levels (nmol g kidney(-1) day(-1)) of dopamine (10.3 +/- 0.5 vs. 8.3 +/- 0.7, P < 0.05) and 3,4-dihydroxyphenylacetic acid (DOPAC) (30.5 +/- 3.7 vs. 21.3 +/- 1.4, P < 0.05) and increases (P < 0.05) in maximal velocity values (Vmax in nmol mg prot(-1) 15 min(-1), 325 +/- 12 vs. 265 +/- 3) for renal aromatic L-amino acid decarboxylase (AADC), the enzyme responsible for the synthesis of renal dopamine. By contrast, in W-CR rats uninephrectomy did not change either the urinary levels of dopamine (7.1 +/- 0.5 vs. 7.6 +/- 0.7) and DOPAC (25.0 +/- 1.9 vs. 24.8 +/- 4.1) or AADC activity (Vmax 199 +/- 3 vs. 193 +/- 9). The Vmax values for renal AADC in W-CR rats were lower than those found in corresponding W-H animals. CONCLUSION: Wistar rats from different suppliers represent an important source of variability in the renal dopaminergic system activity. This may contribute to differences in sodium balance and blood pressure control in response to uninephrectomy.     

Role of hypervolemia and renin in the blood pressure control of patients with pyelonephritis renal scarring

Patients with pyelonephritic renal scarring are at risk of developing renal failure and hypertension. We studied glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF), systolic (SBP) and diastolic (DBP) blood pressure, fractional sodium, potassium and phosphate excretion, peripheral renin activity (PRA), plasma aldosterone (p-Aldo), urinary albumin excretion (U-Alb) and urinary beta 2-microglobulin excretion (beta 2-M) in hydropenia and during transition to 3% volume expansion with isotonic saline infusion in 22 female patients with renal scarring due to pyelonephritis and 9 healthy controls. The patients had significantly lower GFR, higher SBP and higher PRA in hydropenia, but there was no significant difference in RPF, FF, DBP or p-Aldo. After volume expansion, SBP, DBP, PRA and p-Aldo were significantly higher in patients than in controls. Transition to 3% volume expansion was associated with a similar increase in SBP in both patients and controls, whereas DBP increased significantly more in the patients (p less than 0.01). Volume expansion resulted in a significant suppression of PRA and p-Aldo in both patients and controls. The patients with renal scarring had the same capacity to excrete sodium and water during transition to volume expansion as the healthy controls. The renin-aldosterone system seems abnormally activated and is probably more important than hypervolemia in the development of hypertension in this group of patients.     

Constant glomerular filtration rate in diabetic nephropathy. Correlation to blood pressure and blood glucose control

Twenty-one patients with diabetes of type I and diabetic nephropathy with reduced glomerular filtration rate (GFR) were followed prospectively with regard to GFR, proteinuria, blood pressure and glucosylated haemoglobin (HbA1). All patients were on antihypertensive treatment. The mean rate of decline in GFR was only 0.38 ml/month = 4.6 ml/year. In one third of the patients, GFR remained constant at a reduced level for at least 24 months. Mean plasma clearance of 51Cr-EDTA in this group was 48.3 +/- 14.6 ml/min/1.73 m2 body surface at entry and 48.0 +/- 13.6 at the time of evaluation. The patients with constant GFR had significantly less proteinuria and lower systolic as well as mean arterial pressure during the study than patients with falling GFR. They also had significantly lower mean HbA1 and fewer very high HbA1 values than patients who deteriorated. The data thus indicate that a combination of good metabolic control and effective blood pressure control may strongly delay the progression of renal insufficiency in diabetic nephropathy. They also show that low degree of proteinuria is a marker of good prognosis.     

Effect of Arterial Blood Pressure Reduction on Renal Hemodynamics in the Developing Lamb

Aperia , A. and P. Herin . Effect of arterial blood pressure reduction on renal hernodynamics in the developing lamb. Acta physiol. scand. 1976. 98. 387–394. The relationship between pressure and flow in the kidney has been examined in 2–9 and 31–48 day old lambs. Renal blood flow (RBF), determined by the microsphere technique, and glomerular filtration rate (GFR) were first studied under control conditions. The abdominal aorta was then constricted above the renal arteries until the pressure ranged between 60 and 70 mmHg, i.e. just below the normal auto-regulatory range, and the hemodynamic recordings were repeated. During control conditions the arterial pressure was lower in the younger (93 mmHg) than in the older lambs (107 mmHg). During aortic constriction total RBF and GFR were reduced. In both age groups GFR was reduced out of proportion to RBF. The sodium excretion fell around 60% in both age groups. The fall in perfusion pressure resulted in a more pronounced blood flow reduction to the outer than to the inner cortical glomerular capillaries. This pressure-induced blood flow redistribution was found in both age groups. The consequences of the pronounced effect of reducing the perfusion pressure to 60–65 mmHg for the young lambs with their basally low arterial blood pressure are discussed.     

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 AVP-V2 receptor stimulation on local GFR in the rat kidney

The effect of AVP-V2 receptor agonist desmopressin, dDAVP, its non-peptide antagonist OPC-31260 and vehicle infusion on glomerular filtration rate (GFR) in the outer, middle and inner cortex was studied in both hydropenic and water diuretic Inactin anaesthetized female Sprague-Dawley rats using the aprotinin method. Two subsequent GFR measurements were carried out in the same kidney by injection of 125I- and 131I-labelled aprotinin before and after i.v. infusion of dDAVP, OPC-31260 or the vehicle. Acute infusion of dDAVP in hydropenic rats increased total GFR by 14% relative to vehicle infusion, whereas in water diuretic rats it had no effect relative to vehicle. No significant changes in arterial pressure (Pa) or renal blood flow (RBF) were recorded. Infusion of OPC-31260 reduced total GFR by 11% compared with vehicle. These results are consistent with the findings that a presensitization of the vasculature by high plasma levels of AVP is necessary for the renal vascular effects mediated by the V2 or V2-like receptors to occur. The ratio between inner and outer cortex GFR remained unchanged from control to experimental condition as follows: dDAVP infusion in hydropenic rats, 0.504 vs. 0.494 in control; vehicle infusion in hydropenic rats, 0. 393 vs. 0.392; OPC-31260 infusion in hydropenic rats, 0.517 vs. 0. 523; dDAVP in water diuretic rats, 0.547 vs. 0.543; vehicle in water diuretic rats, 0.413 vs. 0.417. Thus no significant difference in the GFR response was observed between superficial and deep cortical layers of the rat kidney.