Renal function during onset of carbachol-induced hypertension in conscious rats

This study evaluated the changes in renal function that occur during the early phases of chronic infusion of carbachol into the lateral ventricle in conscious rats. Infusion of 1.0 micrograms/h of carbachol i.c.v. resulted in a prompt pressor response with mean arterial pressure rising 20 mm Hg within 15 min. The pressure remained elevated for the duration of a 2-hour infusion. Carbachol infusion at 0.5 micrograms/h induced a similar elevation in blood pressure, but the onset was delayed, reaching significance only after 30-60 min. The higher dose of carbachol was associated with a marked and sustained natriuresis, with sodium excretion increasing from 2.1 +/- 0.3 to 5.3 +/- 1.0 microEq/100 g min after 2 h, compared to 2.0 +/- 0.5 and 1.8 +/- 0.3 microEq/100 g min in vehicle-infused control animals. Sodium excretion did not change significantly in animals infused with carbachol at 0.5 microgram/h. There were no significant changes in glomerular filtration rate in any of the groups. Plasma levels of atrial natriuretic peptide (ANP) were not altered significantly by ventricular infusion of carbachol (188 +/- 99 before vs. 83 +/- 17 pg/ml after infusion). It is concluded that the pressor response to central carbachol infusion is not dependent on retention of sodium and water. The natriuresis observed with carbachol infusion can be dissociated from the pressor response, and is not mediated by ANP.     

慢性心力衰竭不同阶段的肾功能损害比较

目的观察慢性心力衰竭不同阶段的肾功能情况。方法将87例我院心内科住院患者分为心衰A~D阶段,A阶段为A组(18例),B阶段为B组(30例),C、D阶段为C组(39例),检测各组肾小球滤过率及24h尿白蛋白含量。结果 B、C组肾小球滤过率较A组低,分别为80.2±4.3,76.0±3.8vs105.2±5.0ml·min-1·1.73m-2,均P<0.05。B、C组24h尿白蛋白含量较A组高,分别为10.9±13.5,24.1±24.2和4.2±2.5μg/ml,各组间比较均P<0.05。结论慢性心力衰竭早期阶段已有肾功能损害。     

新生儿万古霉素不同血药浓度对肾功能的影响

目的 比较新生儿应用万古霉素后不同血药浓度的肾毒性，分析不同血药浓度下万古霉素的安全性。方法 采用回顾性调查方法，收集我院2014年7月1日—2015年6月30日新生儿内科进行万古霉素血药浓度监测的新生儿病例111例。对患儿基本情况、患儿疾病分布、万古霉素血药浓度、病原学检查、药物疗效、合并用药和用药天数、治疗前后肝肾功能等指标进行总结和分析。根据万古霉素血清谷浓度把患儿分为A组(谷浓度<10μg/mL)、Ｂ组(谷浓度10~20μg/mL)和C组(谷浓度＞20μg/mL)。结果 纳入符合标准的患儿111例，万古霉素血清谷浓度<10μg/mL为48例(Ａ组)，10~20μg/mL的有40例(Ｂ组)，>20μg/mL的有23例(Ｂ组)。万古霉素治疗期间有13例发生了与万古霉素相关的肾毒性，其中Ａ组2例(4.17%)，Ｂ组3例(7.5%)，C组8例(34.87%)。结论     

Renal function studies after nephrectomy in renal donors.

Two to six years after they had donated a kidney the 24-hour creatinine clearances of five women and four men had recovered to 85% and 87% respectively of prenephrectomy performance. The male donors had a lower 24-hour creatinine clearance than age-matched controls, but during dextrose and inulin infusion they had similar values for inulin clearance, creatinine clearance, and glucose reabsorption. By contrast, the female donors had significantly reduced clearances both over 24 hours and during infusion, as well as impaired ability to reabsorb glucose. This suggests that potential female donors should be more vigorously investigated before nephrectomy.     

Arterial and venous plasma concentrations of adenosine during haemorrhage.

A haemorrhage model was used to impose severe metabolic stress in anaesthetized cats by removing blood (15.3 ml min-1) to attain an arterial pressure of ca. 50 mmHg for a 2 h period. Adenosine levels in central venous blood rose by 5 min, reached a peak of about 3.5 times control levels by 15 min and then returned to the basal level (1 microM) by 60 min. However, the adenosine concentration in arterial blood remained unchanged for the entire 2 h period of hypotension. These data demonstrate that haemorrhage results in rapid adenosine release, but the released adenosine is not able to serve a role as a systemic circulating vasodilator even in this severe model.     

Renal vasodilator activity of prostaglandin E2 in the rat anaesthetized with pentobarbitone.

1 The effect of intra-aortic administration (i.a.) of prostaglandin E2 (PGE2) on renal blood flow was studied in the rat anaesthetized with pentobarbitone. Renal blood flow was assessed in two ways, either by use of an electromagnetic flow probe or by measurement of the renal clearance of p-aminohippurate (PAH). 2 PGE2 (0.1 microgram/min, i.a.) increased renal blood flow measured by either method. However, PAH clearance overestimated the degree of vasodilatation compared to that obtained using the flow meter. The possibility that PGE2 or a metabolite may increase PAH extraction by the kidney was considered. 3 The sensitivity of the rat to the renal vasodilator actions of PGE2 was enhanced by using a flank retro-peritoneal approach from which to insert the flow probe, rather than a mid-line abdominal incision. 4 Dose-response curves demonstrate that under the conditions used, PGE2 produced a biphasic change in renal vascular resistance, vasodilatation started at 0.01 microgram/min and was maximal at about 3 micrograms/min, while at the highest dose used (20 micrograms/min) PGE2 induced renal vasoconstriction. 5 The results indicate that contrary to previous reports, the rat does not exhibit an important species difference in the response of its renal vasculature to PGE2. Therefore, physiological and pathophysiological roles which have previously been attributed to vasoconstriction produced by PGE2 synthesized in the kidney may now have to be considered.     

Prostaglandin synthetase activity in kidney medulla during the development of experimental hypertension in the rat

Summary The activity of the Pg-E₂-synthetase in the rat renal medulla was observed for a period of 27 days during the development of a hypertension by clamping of the renal artery; an increased activity of Pg-E₂-synthetase with a peak on the 18th day was observed in the kidneys of the 2-kidney model (2-KM=stenosing of the left arteria renalis) and the 1-kidney model (1-KM=stenosing of the left arteria renalis and additional nephrectomy of the right kidney). The initial values of the enzyme activities were reached again on the 21st (1-KM) resp. 24th (2-KM) day post operationem.Abbreviations Pg Prostaglandin - PgE₂ Prostaglandin E₂ - PgE₂-synthetase Prostaglandin E₂-synthetase     

Brain concentrations and synthesis rates of biogenic amines during chronic cobalt experimental epilepsy in the rat

Both the absolute levels and the turnover rates of the monoamines norepinephrine (NE), dopamine (DA), and serotonin (5-HT) were measured in the brains of rats rendered epileptic by the application of cobalt powder to the surface of the cerebral cortex. Throughout the entire 21-day time course studied after cobalt treatment, during which a sustained reduction in the pentylenetetrazol (Metrazol) seizure threshold developed gradually within the first four days, whole brain levels of NE, DA, and 5-HT remained similar to their respective control values. Whereas the turnover rate of NE as well as that of DA in the brains of the cobalt-epileptic rats likewise remained within normal limits, both the rise of brain 5-HT after blockade of its metabolism and its decline from the brain after synthesis blockade followed time courses of change which differed significantly from those of the control groups. The decrease in 5-hydroxyindole acetic acid (5-HIAA) content of the brain caused by blockade of 5-HT catabolism, however, was found to be similar in cobalt-treated and control rats. These results suggest that the involvement of brain biogenic amines in the development and the maintenance of a chronic epileptic state differs markedly from the established role of these potential neurotransmitters in the production of acute seizure activity.     

Sulindac kinetics and effects on renal function and prostaglandin excretion in renal insufficiency

The purpose of this study was to evaluate the pharmacokinetics of sulindac, a purported "renal sparing" nonsteroidal anti-inflammatory drug, and its effects on renal function and prostaglandin excretion in patients with reduced glomerular filtration rate. Twelve female patients (glomerular filtration rate 37 +/- 4 mL/min) were treated with sulindac 200 mg bid for 11 days. Urinary PGE2, 6-keto-PGF1 alpha and serum thromboxane (TxB2) generation were measured by radioimmunoassay (RIA) following extraction on C-18 columns. Glomerular filtration rate and effective renal plasma flow were measured by 99TC-DPTA and 131I-para-aminohippuric acid clearance. In six patients serum and urine levels of sulindac and its metabolites were measured by high-pressure liquid chromatography (HPLC). Sulindac was rapidly absorbed and converted to sulindac sulfide with peak levels 2 hours after a single dose, but steady state levels were not reached prior to drug discontinuation. Sulindac sulfide AUC (0-5 hours micrograms min/mL) progressively increased from 382 to 3,030 on day 11. It did not appear in the urine. Baseline urinary PGE2 and 6-keto-PGF1 alpha excretion were 23.8 +/- 5.6 and 18.9 +/- 2.7 ng/hr respectively and were reduced by 68% and 47% by day 4 of therapy. TxB2 generation fell by 34% after one dose and by 67% by day 11. There was a significant increase in serum creatinine from 1.88 +/- 0.13 mg/dl before treatment to 2.16 +/- 0.15 mg/dL (P less than .05) after eleven days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Altered contractions to endothelin-1, phenylephrine, potassium chloride and relaxations to acetylcholine at various stages of renal hypertension in the rat.

This study is aimed at investigating the contraction and relaxation responses in the thoracic and abdominal aortae at various stages of hypertension. Hypertension in the rats was produced by aortic banding and the responses in the abdominal and thoracic aortic rings were studied 2 and 8 weeks after aortic banding. Contractile responses to phenylephrine ( 10(-6)M), KCl (80 mM) or to endothelin-1 ( 10(-12)to 10(-6)M) and the relaxation responses to acetylcholine ( 10(-7)to 10(-5)M) were similar in the thoracic and abdominal rings of normotensive rats. The intact thoracic rings from 2 week aortic-banded hypertensive rats (ABHR) showed attenuated responses to all the contractile agents used. However, the relaxation to acetylcholine was not altered. In the rings from 8 week ABHR, the responses to contractile agents were not significantly altered but the acetylcholine-induced relaxations were significantly attenuated. The endothelial-derived relaxing factors might act to antagonize the vasoconstrictive responses during the onset of hypertension but might be disabled, as the endothelial dysfunction becomes predominant after 8 weeks of hypertension. The results thus suggest that the contractile and relaxant responses are differentially altered during different stages of hypertension.     

Antihypertensive therapy and arterial function in experimental hypertension

• 1.1. Alterations in the function of the endothelium and arterial smooth muscle may be important in the establishment of hypertension. Thus, the possible favorable influences of blood pressure-lowering agents on vascular responsiveness may be important in the chronic antihypertensive actions of these compounds.
• 2.2. A number of reports have suggested that ACE inhibitors can improve arterial function in hypertension, whereas the knowledge about the vascular effects of other antihypertensive drugs, like β-blockers, calcium channel blockers, and diuretics remains rather limited.
• 3.3. In this article, the effects of antihypertensive therapy on arterial function in human and experimental hypertension are reviewed.

     

Effect of etodolac on the prostaglandin concentrations in the kidney of the normal rat

The effect of acute and subchronic dosing with etodolac on the renal PGE₂ and 6-keto-PGF_1α concentrations in the normal rat were studied. Etodolac and other nonsteroidal antiinflammatory drugs (NSAIDs) were administered orally, at equieffective antiinflammatory doses, to normal rats either as a single dose or as seven daily doses. Whole kidney prostaglandin (PG) concentrations were measured. In the acute study, etodolac (3 mg/kg) did not significantly lower the PGE₂ levels for up to 4 hr postdosing. In contrast, naproxen (3 mg/kg) and piroxicam (0.5 mg/kg) significantly decreased the PGE₂ levels to about 20% and 60% of control, respectively. Similar reductions in 6-keto-PGF_1α concentrations were observed. In the subchronic study, etodolac (3 mg/kg/day) did not lower either PGF₂ or 6-keto-PGF_1α concentrations whereas naproxen (3 mg/kg/day), piroxicam (0.5 mg/kg/day), indomethacin (1 mg/kg/day), and aspirin (300 mg/kg/day) significantlydecreased both PGs. In both studies, the effect of etodolac was significantly different from that of the NSAIDs. It is concluded that etodolac possesses only a very weak capacity to lower renal PGs, and therefore is unlikely to cause any renal complications related to PG biosynthesis inhibition.     

The influence of diltiazem and nifedipine on renal function in the rat.

The effect of intravenous administration of the calcium-entry blocking drugs, diltiazem and nifedipine, on renal haemodynamic and tubular function was examined in denervated kidneys of pentobarbitone-anaesthetized rats. Infusion of vehicle for the compounds had no effect on renal function which was stable for the duration of the experiments. Diltiazem was infused at 5, 10 and 20 micrograms kg-1 min-1. Blood pressure did not change following 5 micrograms kg-1 min-1 diltiazem but was significantly reduced, by 12 mmHg, after 10 micrograms kg-1 min-1 and by 17 mmHg after 20 micrograms kg-1 min-1. Renal blood flow was not affected by any dose of diltiazem while at the lowest dose of drug, glomerular filtration rate (g.f.r.) was significantly increased, by 24%. Absolute and fractional sodium excretion were increased significantly, 154% and 77% respectively, by 5 micrograms kg-1 min-1 diltiazem, 20% and 24% respectively, by 10 micrograms kg-1 min-1 diltiazem, but were unchanged by 20 micrograms kg-1 min-1. Infusion of nifedipine at 0.5, 1.0 and 2.0 micrograms kg-1 min-1 decreased systemic blood pressure by 9, 9 and 20 mmHg, respectively. Renal blood flow was increased (7%) by 1.0 microgram kg-1 min-1 only, while g.f.r. did not change at any dose. Urine flow, absolute and fractional sodium excretions were increased, 127%, 96% and 90% respectively, by 0.5 microgram kg-1 min-1 nifedipine, 127%, 197% and 194% respectively, by 1.0 microgram kg-1 min-1, while these variables remained unchanged by a dose of 2.0 micrograms kg-1 min-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of paraquat and diquat on renal function in the rat.

Both paraquat and diquat are filtered freely by the rat kidney; there is also a small unfiltered component which is actively secreted. Twenty-four hours after a single oral LD50 dose of paraquat (680 μmol/kg), there is a decrease in the glomerular filtration rate (inulin clearance) and in the clearance of acidic (p-aminohippurate, PAH) and basic (N′-methylnicotinamide, NMN, or paraquat) compounds by the kidney. However, over a 2-hr period, no decrease in the excretion of paraquat by the kidney was seen using a range of plasma paraquat concentrations (3–70 nmol/ml). Both inulin and paraquat clearances were decreased in fasted rats, but not fed rats, 24 hr after a subcutaneous LD50 dose of paraquat (108 μmol/kg). Twenty-four hours after a single oral dose of diquat (540 μmol/kg), there is a decrease in inulin clearance and in the clearance of acidic (PAH) and basic (NMN or diquat) compounds by the kidney. Both of these bipyridyls cause hemoconcentration, reducing plasma volume without altering red cell volume. The hemoconcentration observed after these bipyridyls is the result of fluid redistribution into the lumen of the gastrointestinal tract and/or increased diuresis. It is proposed that this fluid loss induces an alteration in renal hemodynamics and a reduction in renal excretory function.     

The effect of prostaglandin E1 during cardiopulmonary bypass on renal function after cardiac surgery

Summary We have evaluated the effect of prostaglandin E₁(PGE₁) on renal function after cardiac surgery with cardiopulmonary bypass in 20 patients, ten of whom received 0.02 g·kg^–1·min^–1 of PGE₁ by infusion into the oxygenator during bypass; ten patients served as controls.Serum ₂-microglobulin fell significantly and urine ₂-microglobulin increased significantly after surgery in both groups. Urine N-acetyl--D-glucosaminidase was high after surgery in both groups, but it was significantly lower in the PGE₁ group. Free water clearance fell significantly on the 1st, 3rd, and 5th postoperative days compared with preoperative values in the control but not in the PGE₁ group.These results suggest that PGE₁ may prevent renal dysfunction after cardiopulmonary bypass.