Inhibition of furosemide-induced renin release by vasoconstrictors

Summary The effect of i. v. infused (asp¹--amid, val⁵)-angiotensin II (1.0 g/kg min), octapressin (phe², lys⁸-vasopressin) (10.0 mU/kg min) and of the -sympathomimetic amine phenylephrine (40.0 g/kg min) on the stimulation of renin secretion by furosemide (10.0 mg/kg i.v.) was investigated. The vasoconstrictors abolished the renin release induced by furosemide. Studies on the clearance of p-aminohippuric acid (PAH) (i.e. renal plasma flow) showed that the action of the vasoconstrictors cannot be explained by a decrease in access of furosemide to its intrarenal sites of action.The mechanism of the suppressive action of the vasoconstrictors on renin release is discussed.Supported by DFG grant Me 541/1.     

Intracellular pH in diluting segment of frog kidney

Chronic exposure to high potassium (K⁺ adaptation) stimulates H⁺ net secretion in the diluting segment of the frog kidney. In order to investigate the cellular mechanism of the H⁺ secretory process intracellular pH (pH_i) measurements were performed in cells of the diluting segment of the isolated doubly-perfused kidney of K⁺ adaptedRana esculenta. pH_i changes were monitored by pH-sensitive microelectrodes while the tubule lumen was rapidly perfused with various solutions. With control solutions (extracellular pH=7.80) pH_i averaged 7.60±0.05. Luminal application of furosemide (5 · 10^–5 mol/l) or reduction of luminal Cl^– (from 104 mmol/l to 9 mmol/l) hyperpolarized the cell membrane potentials but pH_i was not altered. Reduction of luminal Na⁺ (from 98 mmol/l to 3 mmol/l) depolarized the cell membrane potentials but pH_i remained constant. Complete removal of luminal Na⁺, however, led to a significant decrease of pH_i from 7.61±0.08 to 7.18±0.08. Luminal application of amiloride (1 · 10^–3 mol/l) also decreased pH_i significantly (pH_i=0.15±0.02).The results indicate that an amiloride-sensitive H⁺ extrusion mechanism exists in the luminal cell membrane of the K⁺ adapted frog diluting segment. The data are consistent with Na⁺/H⁺ exchange which maintains a constant pH_i even at extreme experimental conditions.Parts of the data were presented at the 16th Ann. Meeting of the Am. Soc. Nephrol., Washington (1983)     

Secretagogues increase apical membrane conductance of isolated bullfrog corneal epithelium pretreated with loop diuretics

Bullfrog (Rana catesbeiana) corneas were mounted in an Ussing type chamber and impaled with an intracellular microelectrode and the short circuit current was inhibited by pretreatment with the loop diuretics furosemide (0.3 to 1 mM) or bumetanide (10 to 100 M). Subsequent addition of the secretagogues prostaglandin E₂, forskolin, or 3-isobutyl-1-methylxanthine (IBMX) caused the fractional voltage drop of the apical barrier to decrease from 0.72±0.05 to 0.48±0.04 and the chloride-dependent conductance to increase by 0.15±0.03 mS/cm², but caused only a small, transient increase in short circuit current. The loop diuretics by themselves always greatly reduced the short circuit current but did not consistently reduce conductance or fractional voltage drop of the apical membrane. Because the secretagogues were able to increase the apical membrane conductance of diuretic-inhibited corneas without large effects on the short circuit current, the loop diuretics must have a major effect at a site other than the apical membrane Cl^– conductance, presumably at the basolateral membrane. An additional effect of the loop diuretics at the apical membrane is also possible.A preliminary account of this work was presented at the annual meeting of the Association for Research in Vision and Ophthalmology, May, 1988 [Invest Ophthalmol Vis Sci 29 (Suppl):174]     

The voluntary correction of sodium deficiency by the rabbit

The behaviour involved in the correction of sodium deficit has been studied in wild rabbits and also laboratory bred rabbits. They were offered 0.5 M NaCl to drink. In adrenalectomized wild rabbits variable sodium deficits were produced by withdrawal of mineralocorticoid for 24-72 hr. Correction of the deficit was remarkably precise and was achieved in 9-24 hr, being slower with smaller deficits. That is, the rate of drinking was almost commensurate with the degree of body deficit. No overdrinking occurred by 24 hr. Repetition of the experiment with 24 hr deficiency and with the offer of a cafeteria of 0.5 M NaCl, 0.5 M KCl, 0.25 M CaCl2 and 0.25 M MgCl2 showed the increased appetite was specific for NaCl. Both wild and laboratory rabbits, adrenally intact, were made sodium deficient by the diuretic furosemide. Voluntary salt intake did not peak until 6-12 hr later reflecting the characteristic delay in the genesis of salt appetite. If presentation of salt were delayed 24 hr after furosemide, the highest rate of intake was seen immediately in both wild and laboratory rabbits, but the wild rabbits were much faster in fully correcting body deficit. Infusion of isotonic NaCl, adequate to correct the deficit, given during the third-sixth hour of access to NaCl under the 24 hr delay of presentation regime, halved salt appetite over this period, and by 9-12 hr it was abolished. Polyethylene glycol induced subcutaneous fluid sequestration, salt appetite and thirst but caused an obvious severe deterioration in the animals condition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renin-hyporesponsiveness in essential hypertension dissociation between plasma renin and catecholamines or aldosterone following furosemide

Summary The influences of sequential stimulation with upright posture and sodium depletion by intravenous furosemide on blood levels of norepinephrine, epinephrine, dopamine, renin and aldosterone was studied in 26 normal subjects and 45 patients with borderline (N=20) or established (N=25) essential hypertension. Basal 24-h urinary sodium, norepinephrine and epinephrine excretion rates and basal (supine) plasma catecholamine, renin and aldosterone levels and the body sodium-volume state were comparable between the three groups. Assumption of the upright posture for 10 to 60 min caused significant increases in plasma norepinephrine (P<0.001), epinephrine (P<0.001) or dopamine (P<0.05) levels. Upright plasma catecholamine concentrations were similar in normal and hypertensive subjects and they were not modified further by furosemide. In contrast upright posture as well as furosemide induced each a successive significant (P<0.02) increase in plasma renin and aldosterone levels. Furosemide-stimulated renin was significantly (P<0.05) lower in patients with established hypertension than in normal or borderline hypertensive subjects; however, plasma aldosterone levels were comparable. These findings suggest that renin release induced by furosemide is not mediated by increased adrenergic activity. Consequently, renin-hyporesponsiveness in established hypertension cannot be explained by decreased sympathetic activity. In contrast to the altered renin regulation, aldosterone-responsiveness to upright posture or furosemide as well as adrenergic activity under these conditions appear to be usually normal in borderline or established hypertension.Supported by the Swiss National Science Foundation     

Coupling of metabolic CO2 production to ion transport in isolated rat thick ascending limbs and collecting tubules

Metabolic CO₂ production from appropriate [U-¹⁴C]-labelled substrates (eitherl-lactate ord-glucose) was measured in single pieces of tubule as previously described (Le Bouffant et al. 1984). Changing the incubate osmotic pressure by mannitol addition resulted in an increase in oxidative metabolism which was more marked in outermedullary segments (MAL and MCT) than in cortical segments (CAL and CCT). Availability of metabolic substrate was not rate limiting under these conditions because FCCP addition (1 mol·l^–1) produced a marked rise in CO₂ production in these structures.Ouabain (1 mmol·l^–1) decreased by more than 50% the CO₂ production by CAL, MAL, CCT and MCT samples, indicating that the larger part of oxidative metabolism was coupled to active Na transport. Furosemide addition (10^–5 mol·l^–1) to CAL and MAL samples, or amiloride addition (10^–4 mol·l^–1) to CCT and MCT samples reduced the rate of CO₂ production to an extent almost similar to that obtained with ouabain, an observation suggesting that apical entry of Na⁺ was present in these non-perfused tubules.Finally, the effects of changing the concentration of either K⁺ or Cl^– was tested in CAL samples. K⁺ suppression greatly depressed the rate of CO₂ production. Replacement of chloride with sulfate also decreased this rate to an extent similar to that observed with furosemide. The CO₂ production increased in a sigmoid way (apparentK _a=41 mmol·l^–1, Hill coefficient=2.12) as a function of [Cl^–] in the incubate, suggesting that oxidative metabolism was coupled to bath chloride via the Cl^–-requiring Na entry along the 1 Na⁺–1K⁺–2Cl^– luminal contrasport system.     

Influence of three different types of hypercalciuria on bone

 The relationship between bone mineral status and hypercalciuria is controversial. The effect on bone composition of different forms of hypercalciuria was studied in female rats made hypercalciuric by 7-week administration of oral furosemide (F, n=12), intraperitoneal 1,25-dihydroxy vitamin D (VD, n=11), or oral ammonium chloride (AC, n=12). Seven untreated rats served as controls (C). Hypercalciuria (mg/100 g per 24 h, mean ±SEM) of F (4.3±0.2), VD (4.1±0.4), and AC (3.9±0.3) groups was of similar intensity (C rats 1.3±0.1, P<0.01). Weight and length gains and serum CO₂, sodium, potassium, calcium, and phosphate were no different among the four groups. Bone was studied by dual-energy X-ray absorptiometry of left tibiae. AC rats had significantly less bone area (1.505±0.018 cm²) than VD and C (1.602±0.020 and 1.587±0.019 cm²). Bone mineral content was decreased in F (0.357±0.007 g) and AC (0.362±0.006 g) compared with VD (0.407±0.008 g) and C (0.389±0.009 g) groups. Bone mineral density was different between F (0.231±0.002 g/cm²) and VD and C rats (0.254±0.004 and 0.245±0.003 g/cm²), and also between AC (0.240±0.003 cm²) and VD rats. In these rat models, hypercalciuria of renal origin (F) and hypercalciuria caused by acid load (AC) adversely impaired bone mass. Received: 19 September 1997 / Revised: 28 July 1998 / Accepted: 29 July 1998     

利尿合剂治疗顽固性心力衰竭120例疗效观察

目的 观察利尿合剂治疗顽固性心力衰竭患者临床疗效及安全性.方法 将120例顽固性心力衰竭患者完全随机分为治疗组和对照组各60例,2组患者均给予利尿剂、血管紧张素转换酶抑制剂、硝酸酯类药物、控制感染及纠正水、电解质紊乱和洋地黄等治疗.治疗组加用利尿合剂,观察7d,对比2组的临床疗效.结果 治疗组与对照组总有效率分别为91.7％(55/60)、71.7％ (43/60),总有效率差异有统计学意义(x2 =8.541,P＜0.05).结论 顽固性心力衰竭患者常规治疗效果不佳,联合应用利尿合剂可显著提高疗效,安全经济,值得推广.     

64层螺旋CT正常上尿路造影：俯卧位、呋塞米对显影的价值

目的：通过比较64层螺旋CT泌尿系统造影,几种方法对正常上尿路显影的效果,探讨俯卧位及静脉注射呋塞米对显影的价值。方法：57例泌尿系统正常样本,随机采用以下延迟方法：大量饮水仰卧位,大量饮水俯卧位,注射呋塞米。上尿路分为5段（肾盏,肾盂,近、中、远段输尿管）,对每段显影程度予以评分,采用SPSS 11.0统计软件行方差分析。结果：①饮水俯卧位仅对中段输尿管的显影评分优于仰卧位,但无显著性;②呋塞米组各段几乎全部显影,对中段输尿管的显影显著优于饮水仰卧位,与俯卧位无显著性差异,对远段输尿管的显影显著优于饮水（仰卧、俯卧位）组。结论：与仰卧位相比俯卧位可以提高中段输尿管的显影,但价值有限。静脉注射小剂量呋塞米的显影效果最佳,可临床推广应用。