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C B Nielsen

Publications and source records attributed to C B Nielsen.

At least 19 recordsLinked to original sources
PubMed1999

The systemic and renal response to NO inhibition is not modified by angiotensin-II-receptor blockade in healthy humans.

BACKGROUND: The role of angiotensin II (Ang II) in the systemic and renal responses to acute nitric oxide (NO) synthesis inhibition has not been studied in detail in healthy humans. The purpose of the present study was to investigate the effects of Ang II receptor blockade on the systemic and renal response to acute treat ment with Ng-monomethyl-L-arginine (L-NMMA) in healthy subjects. METHODS: Mean arterial blood pressure (MAP), renal plasma flow (RPF), glomerular filtration rate (GFR), sodium excretion (UNa*V), and plasma levels of renin, Ang II, ANP, BNP, and cGMP were assessed in 15 healthy sodium replete humans before and after acute L-NMMA treatment (3 mg/kg) on two occasions, i.e. after pretreatment with the Ang II type 1 receptor (AT-1) antagonist candesartan cilexetil (CAND; 8 mg) or placebo in a double blind, randomized fashion. Renal haemodynamics were measured during water diuresis using renal clearances of [125I]hippuran and [51Cr]EDTA. Plasma hormones were measured by radioimmunoassays. RESULTS: On both study days L-NMMA treatment induced a significant increase in MAP and a significant decrease in GFR, RPF, and UNa*V. These effects of L-NMMA were not affected significantly by pretreatment with CAND. The effects of L-NMMA on hormones were roughly similar on both occasions with a drop in P-cGMP and U-cGMP. However, a fall in renin was observed only during CAND pretreatment. CONCLUSIONS: We conclude that Ang II is not a major mediator of acute vasoconstriction and sodium retention during acute lowering of NO activity in healthy man.

Adult↗
PubMed1999

Under control of the Ren-1c promoter, locally produced transforming growth factor-beta1 induces accumulation of glomerular extracellular matrix in transgenic mice.

Our purpose was to elucidate the hypothesis that paracrine-produced transforming growth factor (TGF)-beta1 regulates the accumulation of extracellular matrix (ECM) in renal glomeruli, a hallmark of diabetic nephropathy. To produce TGF-beta1 from the juxtaglomerular apparatus in mouse kidneys, we cloned a mouse Ren-1c promoter fragment (-4.100 to +6 base pairs) upstream of porcine TGF-beta1 (pTGF-beta1) cDNA, mutated to ensure secretion of biologically active TGF-beta beta1. The resulting transgenic mice had significantly more TGF-beta1 in their kidneys than was in those of nontransgenic controls, as confirmed by immunohistochemistry, and the production of TGF-beta1 was enhanced in vivo by captopril-induced stimulation of the Ren-1c promoter. Overproduction of pTGF-beta1 close to the glomerulus resulted in a local accumulation of ECM, composed partly of collagen type IV and laminin, and thickening of the basement membrane, characteristic features of diabetic nephropathy. Interstitial accumulation of ECM and signs of tubular atrophy were present only in older mice (>5 months of age). Results from in situ hybridization and immunohistochemistry suggest that pTGF-beta1 stimulated the production of endogenous TGF-beta1 along collecting ducts and connecting tubules. The increased amount of biologically active TGF-beta1, transgenic as well as endogenous, was corroborated by heightened proteoglycan synthesis from incubated kidney slices. This transgenic model demonstrates that sustained local expression of TGF-beta1 leads to glomerulopathy. We conclude that autocrine- or paracrine-produced TGF-beta1 may play a role in the development of glomerular diseases, such as diabetic nephropathy.

Animals↗
PubMed1998

Dietary sodium affects systemic and renal hemodynamic response to NO inhibition in healthy humans.

Animal studies have indicated that increased nitric oxide (NO) synthesis plays a significant role in the renal adaptation to increased sodium intake. To investigate the role of NO during increased sodium intake in humans, we studied the effect of acute, systemic injection of NG-monomethyl-L-arginine (L-NMMA) on renal hemodynamics [glomerular filtration rate and renal plasma flow (GFR and RPF, respectively)], urinary sodium excretion (FENa), systemic hemodynamics [mean arterial blood pressure and heart rate (MAP and HR)], and plasma levels of several vasoactive hormones in 12 healthy subjects during high (250 mmol/day) and low (77 mmol/day) sodium intake in a crossover design. The sodium diets were administered for 5 days before the L-NMMA treatments, in randomized order, with a washout period of 9 days between each diet and L-NMMA treatment. GFR and RPF were measured using the renal clearance of 51Cr-labeled EDTA and 125I-labeled hippuran by the constant infusion technique in clearance periods of 30-min duration. Two baseline periods were obtained, after which L-NMMA was given (3 mg/kg over 10 min), and the effect of treatment was followed over the next five clearance periods. During high sodium intake, L-NMMA induced a more pronounced relative decrease in RPF (P = 0.0417, ANOVA), a more pronounced relative decrease in FENa (P = 0.0032, ANOVA), and a more pronounced relative increase in MAP (P = 0.0231, ANOVA). During low sodium intake, the effect of L-NMMA on FENa was abolished. During low sodium intake, L-NMMA induced a sustained drop in plasma renin (31 +/- 5 vs. 25 +/- 5 microU/ml, P < 0.001), which was not seen during high sodium intake. The data indicate that increased production of NO is an important part of the adaptation to increased dietary sodium intake in healthy humans, with respect to renal hemodynamics, sodium excretion, and the secretion of renin.

Adult↗
PubMed1997

Effects of prostacyclin on renal haemodynamics, renal tubular function and vasoactive hormones in healthy humans. A placebo-controlled dose-response study.

AIMS: To investigate the acute effects of prostacyclin (Flolan) on renal haemodynamics, renal tubular function, plasma concentration of angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP), arginine vasopressin (AVP), mean arterial blood pressure (MBP), and heart rate (HR). METHODS: Thirteen healthy control subjects were investigated on two separate occasions in a placebo controlled, randomized, dose-response study of the effect of intravenous infusion of prostacyclin (PGI2, Flolan, 2, 4 and 8 ng kg(-1) min(-1)). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the use of constant infusion of [51Cr]-EDTA and [125I]-hippurane. Urinary output, urinary sodium excretion, fractional sodium excretion, fractional lithium excretion were measured and hormones were measured using radioimmunoassay. RESULTS: During prostacyclin (PGI2) infusion we observed a significant increase in RPF (PGI2: 4.8%; 6.1% and 5.2% vs Plac: -1.5%; -1.9% and -5.8% for 2, 4 and 8 ng kg(-1) min(-1) respectively; P < or = 0.05 for 4 and 8 ng kg(-1) min(-1)) in Ang II (PGI2: 20.0%; 42.9% and 88.9% vs Plac: 0.1%; 8.0% and 0.0%, P < or = 0.01 for 4 and 8 ng kg(-1) min(-1)) in ANP (PGI2: 13.6%; 12.7% and 37.5% vs Plac: -10.2%; -6.6% and -2.4%, P < or = 0.05 for 2 ng kg(-1) min(-1) and P < or = 0.01 for 4 and 8 ng kg(-1) min(-1)), and in HR (PGI2: 8.8%; 17.6% and 32.7% vs Plac: 0.8%; 4.1% and 3.5%, P < or = 0.05 for 2 and P < or = 0.01 for 4 and 8 ng kg(-1) min(-1)). A significant decrease was observed in MBP (MBP:PGI2: -1.7%; -1.9% and -5.6% vs Plac: -0.4%; -1.6% and +2.1%, P < or = 0.01 for 8 ng kg(-1) min(-1)). No significant changes were seen in the other effect variables. CONCLUSIONS: Infusion of prostacyclin in healthy control subjects increases renal plasma flow, angiotensin II, atrial natriuretic peptide, and heart rate and decreases mean blood pressure. Furthermore prostacyclin infusion does not change net sodium excretion in healthy controls.

Adult↗
PubMed1997

Impaired renal haemodynamic response to amino acid infusion in essential hypertension during angiotensin converting enzyme inhibitor treatment.

OBJECTIVE: To determine whether hyperfiltration induced by amino acid infusion can be influenced by angiotensin converting enzyme (ACE) inhibition. DESIGN: We studied the acute effects of ramipril in 12 healthy control subjects and in 14 patients with essential hypertension. We studied also the effects of 2 months' treatment with ramipril inn 12 patients with essential hypertension and performed a time-control study without amino acids infusion with 12 control subjects. The glomerular filtration rate (GFR), renal plasma flow (RPF), fractional excretion of sodium (FENa) and fractional excretion of lithium (FELi) were determined during 6 clearance periods of 30 min each and amino acids infusion was administered during the last four periods. Plasma concentrations of angiotensin II, aldosterone, atrial natriuretic peptide (ANP), arginine vasopressin, insulin and glucagon were determined. RESULTS: Both the GFR and the RPF increased markedly in healthy subjects after amino acid infusion both with (GFR 7%, RPF 7%) and without ramipril (GFR 7%), RPF 8%), both P < 0.05. Ramipril administered acutely to essential hypertensives prevented the amino acid-induced increase in RPF [with ramipril 5% (NS), without ramipril 9% (P < 0.05)]. The GFR increased equally with (5%) and without (8%) ramipril (P < 0.20). ACE inhibition after 2 months' treatment of essential hypertension blunted the amino acid-induced increase both in GFR and in RPF [with ramipril GFR 5% and RPF 3% (NS), without ramipril GFR 12%, RPF 11% (P < 0.05)]. The FENa did not change in all four experiments. The FELi, insulin and glucagon increased to the same extent in the first three experiments. ANP increased (P < 0.05) in control subjects both with and without ramipril; angiotensin II and aldosterone decreased significantly in control subjects without ramipril. CONCLUSIONS: The renal haemodynamic response both after acute and after short-term ACE inhibition is attenuated in essential hypertension. Presumably, this treatment makes the arterioles at the glomeruli unresponsive to subsequent amino acid infusion. This inhibition of hyperfiltration might be an important mechanism for the renal protective effect of ACE inhibition in some renal diseases.

Adult↗
PubMed1997

A comparison of the effect of ramipril, felodipine and placebo on glomerular filtration rate, albuminuria, blood pressure and vasoactive hormones in chronic glomerulonephritis. A randomized, prospective, double-blind, placebo-controlled study over two years.

The effects of an ACE-inhibitor (ramipril), a calcium antagonist (felodipine) and placebo on glomerular filtration rate (GFR), urinary albumin/creatinine ratio, blood pressure (BP) and vasoactive hormones were investigated in a randomized, prospective, double-blind, placebo-controlled study of patients with chronic glomerulonephritis and hypertension, with measurements at entrance and after 12 and 24 months. In total, 33 patients were included: 21 completed the study with 7 patients in each group. GFR was measured as 51Cr-EDTA clearance and the vasoactive hormones with radioimmunoassays. The reduction in GFR was significantly more pronounced in the felodipine group (-7 ml/min) than in the ramipril group (0 ml/min) but the same as in the placebo group (-6 ml/min). The urinary albumin/creatinine ratio was significantly more reduced in the ramipril group (-74 mg/mmol) than in the placebo group (-11 mg/mmol), which did not deviate from the felodipine group (-10 mg/mmol). BP was significantly reduced by ramipril and felodipine, but not by placebo. Angiotensin II and aldosterone in plasma increased or tended to increase in the felodipine and placebo groups, but were unchanged in the ramipril group. Endothelin increased only in the placebo group, and vasopressin, atrial natriuretic peptide, and brain natriuretic peptide were not significantly changed in any of the groups. It is concluded that ramipril seems to be superior to felodipine in chronic glomerulonephritis owing to better preservation of GFR.

Adolescent↗
PubMed1997

Heart function in patients with chronic glomerulonephritis and mildly to moderately impaired renal function. An echocardiographic study.

UNLABELLED: Left ventricular hypertrophy and diastolic heart dysfunction have been reported in essential hypertension and in patients with chronic renal failure, treated with haemodialysis, but a close association with blood pressure (BP) level has not been uniformly documented. Thus, other factors could be involved in the pathogenesis of cardiac dysfunction. The aims of the present echocardiographic study were to investigate cardiac morphology and function in patients with chronic glomerulonephritis with mildly to moderately impaired renal function, and to study the relation between echocardiographic findings and glomerular filtration rate (GFR), BP and age. Twenty patients with chronic glomerulonephritis and 14 healthy controls, of the same age- and sex-distribution, were examined by 2D-, M-mode and pulsed-wave Doppler echocardiography. In patients, GFR was determined as plasma clearance of Cr-EDTA. The patients had significantly thicker left ventricular (LV) posterior walls in end diastole (8.7 vs 8.1 mm, p < 0.05), and a higher LV mass index (106.5 vs 93.8 g/m2, p < 0.05). Systolic functional indices, i.e. LV fractional shortening and LV ejection fraction, were statistically significantly lower in patients than in controls (p < 0.05). LV diastolic function in patients was characterized by a statistically significantly lower early peak flow velocity (E-Vmax) (0.66 compared with 0.8 m/s) and early to late peak flow velocity ratio (E/A ratio) (1.07 vs 1.41), as well as E/A ratio of time velocity indices (VTI-E/A) (1.45 vs 1.99) (p < 0.05). The right ventricular filling indices showed a tendency towards a lower E-Vmax in patients (0.55 compared with 0.62 m/s, p = 0.1). In patients, statistically significant negative correlations were found between age and mitral E/A ratio (r = -0.76, p < 0.0001), as well as LV VTI-E/A(r = -0.81, p < 0.0001). The same trend was seen for the tricuspid E/A ratio. No statistically significant correlations were found in patients between mitral or tricuspid E/A ratio and GFR, BP, LV mass or heart rate. IN CONCLUSION: in a group of patients with chronic glomerulonephritis and mildly to moderately impaired renal function, it was found by means of echocardiography that there was a higher LV mass index and decreased systolic function, when compared with healthy controls. In addition, the patients had diastolic dysfunction of primarily the left ventricle. The echocardiographic findings were not correlated to BP level or renal function. This suggests that factors other than GFR or BP per se might be involved in the pathogenesis of cardiac dysfunction, at an early stage.

Adult↗
PubMed1997

Abnormal distal tubular sodium reabsorption during dopamine infusion in patients with essential hypertension evaluated by the lithium clearance methods.

The effects of low-dose dopamine infusion on renal hemodynamics, tubular function estimated by the lithium clearance technique and plasma levels of angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) were studied in 11 patients with essential hypertension (HT) and in 10 healthy control subjects (CS). Antihypertensive treatment was terminated at least 2 weeks prior to examination. Dopamine (2 micrograms/kg/min) was infused for two hours. Before dopamine infusion all measured parameters, but blood pressure, did not deviate significantly between the two groups, including 24 h urinary sodium excretion prior to investigation (HT: 166.9 mmol/24 h vs. CS: 183.4 mmol/24 h, medians). Dopamine infusion resulted in an exaggerated natriuresis in the HT group when compared with the CS group; sodium excretion: (HT: from 260 to 759 mumol/min vs. CS: from 255 to 432 mumol/min, p < 0.01) and fractional sodium excretion: (HT: from 1.6 to 4.2% vs. CS: from 1.6 to 2.4%, p < 0.01 median values). Distal fractional sodium reabsorption was significantly lower in the HT patients (HT: from 94.0 to 88.5% vs. CS: from 94.0 to 91.6%, p < 0.01). ANP decreased significantly only in the HT group (HT: from 4.8 to 3.5 pmol/l vs. CS: from 3.2 to 3.4 pmol/l, p < 0.01). Renal hemodynamics, blood pressure, urinary output, Ang II, Aldo, and AVP were changed to the same degree or unchanged in both groups. It is concluded that the exaggerated natriuretic response seen in patients with essential hypertension during low-dose dopamine infusion probably is due to a enhanced dopamine sensitivity mainly in the distal parts of the nephron.

Adult↗
PubMed1996

Epoprostenol increases plasma level of atrial natriuretic peptide in humans.

1. In a placebo-controlled, randomized dose-response study the effect of the prostaglandin analogue epoprostenol (Flolan) on the plasma level of atrial natriuretic peptide has been investigated in 14 healthy control subjects. 2. During epoprostenol infusion, atrial natriuretic peptide increased significantly in a dose-dependent manner, while it remained unchanged during placebo infusion [2 ng min-1 kg-1: epoprostenol 13.2% versus placebo -2.9%; 4 ng min-1 kg-1: epoprostenol 13.4% versus placebo -6.1%; 8 ng min-1 kg-1: epoprostenol 40.7% versus placebo -7.8% (medians), P < 0.01 for all]. 3. Mean blood pressure and heart rate increased significantly after epoprostenol, but were unchanged during placebo infusion [8 ng min-1 kg-1; mean blood pressure: epoprostenol -5.6% versus placebo 3.2%; heart rate: epoprostenol 32.7% versus placebo 3.1% (medians), P < 0.01]. 4. It is concluded that epoprostenol given intravenously increases the plasma level of atrial natriuretic peptide. The results support the hypothesis of an interaction between the prostaglandin system and atrial natriuretic peptide.

Adult↗
PubMed1996

Renal and hormonal actions of atrial natriuretic peptide during angiotensin II or noradrenaline infusion in man.

In order to study the renal and hormonal actions of atrial natriuretic peptide (ANP) during background infusions with angiotensin II (ANG II) or noradrenaline (NA), 69 healthy subjects were examined in three main groups receiving a 90-min infusion with either placebo, ANG II (1.5 ng kg-1 min-1), or NA (25 ng kg-1 min-1). Each of these three main groups were subdivided into two groups receiving an infusion with either placebo or ANP (10 ng kg-1 min-1) for the last 60 min of the background infusion. Lithium clearance was used to evaluate segmental tubular reabsorption. ANG II alone caused a decrease in glomerular filtration rate (GFR), renal plasma flow, urinary absolute and fractional excretion of sodium, both proximal and distal fractional tubular sodium reabsorption, and urinary flow. NA alone caused a decrease in renal plasma flow. ANP alone caused a decrease in renal plasma flow. Urinary absolute and fractional excretion of sodium were increased and the distal fractional tubular reabsorption of sodium decreased, whereas the proximal fractional tubular reabsorption was unchanged by ANP. ANG II + ANP: during a background ANG II infusion, ANP still increased fractional excretion of sodium. Proximal fractional reabsorption was decreased, whereas distal fractional reabsorption of sodium was unchanged by ANP during ANG II infusion. The ANP-induced decreases in proximal absolute (-147 vs. +714 mumol min-1 1.73 m-2, P = 0.05) and fractional (-1.7% vs. +0.6%, P < 0.01) tubular sodium reabsorption were more pronounced, and the decrease in distal fractional tubular reabsorption of sodium (-0.1% vs -1.4%, P < 0.05) less pronounced compared with when ANP was given alone. NA + ANP: during a background NA infusion, ANP still increased urinary sodium excretion and decreased distal fractional reabsorption. None of the ANP-induced absolute changes seen during background infusion with NA were significantly different from the ANP-induced changes seen during placebo background infusion. It is concluded that the natriuretic action of low-dose ANP seems to be preserved during background infusions with ANG II and NA in man. Net sodium excretion during the combined infusion with ANG II and ANP seems to reflect the sum of the opposing influences of each peptide. Low-dose ANP had a very modest but significant inhibitory effect on proximal tubular sodium reabsorption prestimulated by ANG II infusion.

Adult↗
PubMed1996

The acute effects of FK-506 on renal haemodynamics, water and sodium excretion and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide and vasopressin in pigs.

FK-506 has been shown to be an effective immunosuppressive drug with possible nephrotoxic side effects. In this study we have investigated the acute effects of FK-506 on renal haemodynamics, water, sodium and lithium excretion rates and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide (ANP) and vasopressin in 29 anaesthetized Lancaster/Yorkshire female pigs. A continuous intravenous infusion was given over a 2-h period to 4 groups: A: 0.075 mg kg-1 (n = 7), B: 0.15 mg kg-1 (n = 8), C: 0.3 mg kg-1 (n = 6) and P: placebo vehicle (n = 8). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion clearance technique using 125-I-iothalamate and 131-I-hippuran as reference substances. Hormonal parameters were measured by radioimmunoassay. In all three FK-506 groups, fractional lithium excretion was significantly decreased 2 h after FK506 infusion (P: +0.4%, A: -8.8% (P < 0.05), B: -12.9% and C: -11.2% (P < 0.01 for both). Mean arterial blood pressure (MBP) was significantly increased in the two highest dosage groups (B,C) at 2 h of infusion: (MBP; P: +2.9%, A: +3.5%, B: +12.0%, C: +15.3% (P < 0.01 for both). GFR and RPF showed minor and inconsistent changes while all other parameters measured showed similar or no changes. In conclusion, acute infusion of FK-506 to pigs does not change overall renal function significantly, but increases mean arterial blood pressure and decreases fractional excretion of lithium.

Aldosterone↗
PubMed1996

Effects of systemic NO synthesis inhibition on RPF, GFR, UNa, and vasoactive hormones in healthy humans.

Animal studies have implicated an important role of nitric oxide (NO) in the regulation of blood pressure, renal hemodynamics, and renal excretion of sodium. NG-monomethyl-L-arginine (L-NMMA) is a specific, competitive inhibitor of NO synthesis interfering with NO synthase. The purpose of the present study was to investigate the effect of L-NMMA on renal plasma flow (RPF), glomerular filtration rate (GFR), urinary sodium excretion (UNa), fractional sodium excretion (FENa), fractional lithium excretion (FELi), mean arterial blood pressure (MAP), and heart rate (HR) in healthy humans. In a randomized placebo-controlled study, 23 healthy subjects were randomized to receive either bolus injection of L-NMMA (3 mg/kg in 10 ml saline, n = 12 subjects) or placebo (10 ml saline, n = 11). GFR and RPF were measured using the renal clearances of 51Cr-labeled EDTA and 125I-labeled hippuran by the constant infusion technique. L-NMMA treatment induced 60 min after injection a 14.6% decrease in RPF, a 5.8% decrease in GFR, a 9.8% increase in filtration fraction, a 34.7% decrease in UNa a 28.6% decrease in FENa, and a 12.1% decrease in FELi. These changes were still evident 120 min after injection. None of the effect parameters were changed after placebo, except FENa, which increased 9.9% 60 min after injection. Ten minutes after L-NMMA injection, MAP increased significantly (80 vs. 88 mmHg), and HR decreased (58 vs. 47 beats/min). The changes in HR and MAP normalized within 30 min. L-NMMA significantly reduced the plasma level of cGMP 60 min (3.0 vs. 3.7 pmol/l) and 120 min after injection (2.5 vs. 3.7 pmol/l). It is concluded that, in healthy humans, NO is a regulator of renal hemodynamics as a tonic vasodilator and a regulator of sodium excretion, due at least in part to a proximal tubular effect.

Adult↗
PubMed1995

[Problem-based medical teaching].

A possible method of improving teaching at faculties of Health Sciences is the so-called problem-based teaching method. A student is presented with a (clinical) medical case, which is to be investigated. By means of this method, the student himself will, under guidance, formulate his individual lack of knowledge, goals, priorities, methods, and evaluation. Educational observations show that the learning process is better when the problem-solving takes place among a group of students. A tutor acts as a catalyst for the process and gives feed-back through the problem-solving. He is therefore not an intermediary of knowledge to the group, but primarily refers the student to literature or knowledge experts at the faculty. International studies have not proven any unequivocal improvement in the students' ability to pass exams or to work as doctors, but both teachers and students seem to be more satisfied with the teaching method, which has stimulated the wish to study. The use at other faculties has not caused any large increase in expenditures. This should result in an increased use of problem-based teaching in medical education.

Denmark↗
PubMed1994

Effects of rapamycin on renal hemodynamics, water and sodium excretion, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide, and vasopressin in pigs.

We have investigated the acute effects of rapamycin on renal hemodynamics, water, sodium and lithium excretion rates, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide and vasopressin in 34 Lancaster/Yorkshire female pigs, a breed that has a renal structure/function resembling that of the human kidney. Three different dosages were given over a 1-hr period: dose A, 0.1 mg/kg (n = 8); dose B, 0.2 mg/kg (n = 8); dose C, 0.4 mg/kg (n = 8); and P, placebo vehicle (n = 10). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by constant infusion clearance technique using 125I-iothalamate and 131I-hippuran, and hormonal parameters were measured by RIA. Renal hemodynamics, water and sodium excretion rates, and tubular function, evaluated by the lithium clearance technique, were unchanged both during and up to 2 hr after rapamycin infusion, although GFR and RPF increased when rapamycin was given in supratherapeutic dosages of 0.4 mg/kg (GFR: P, 4.4%; A, 7.9%; B, 2.5%; C, 13.3% [P < 0.05]; RPF: P, 7.1%; A, 4.9%; B, 3.9%; C, 15.3% [P < 0.01], median values). It is concluded that infusion of rapamycin has no acute deleterious effects on renal function in pigs in therapeutic to supratherapeutic dosages.

Aldosterone↗
PubMed1994

Identical effects of indomethacin on renal function in healthy uninephrectomized subjects and in healthy control subjects.

1. Animal studies have shown that prostaglandins are important for renal function after unilateral nephrectomy. In order to investigate the importance of prostaglandins for renal function in the fully adapted remnant kidney in healthy uninephrectomized subjects, the acute effects of indomethacin on renal haemodynamics, lithium clearance, urinary excretion rates of prostaglandin E2, sodium and water, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide and arginine vasopressin were measured in 14 healthy uninephrectomized subjects (median time after nephrectomy 1.7 years) and in 14 matched healthy control subjects. In addition, nine healthy control subjects were studied without indomethacin and served as a time-control group. 2. Before indomethacin ingestion there was a significantly higher single-kidney urinary excretion rate of prostaglandin E2 in the uninephrectomized group (uninephrectomized group, 349.2 fmol/min; control group, 76.6 fmol/min; time-control group, 96.3 fmol/min). 3. Indomethacin ingestion resulted in equal changes in all parameters in both groups. These were significant decreases in glomerular filtration rate (-11.3% versus -14.6%), renal plasma flow (-6.5% versus -13.0%), urinary flow rate (-49.8% versus -49.4%), fractional sodium excretion (-44.5% versus -47.4%), lithium clearance (33.2% versus -23.8%) and urinary excretion rate of prostaglandin E2 (-93.8% versus -86.7%) (uninephrectomized versus control subjects, values are medians). In the time-control group no changes were observed in these parameters. 4. It is concluded that healthy uninephrectomized subjects with a fully adapted remnant kidney have a normal renal response to acute indomethacin-induced inhibition of prostaglandin synthesis.

Adult↗
PubMed1994

Pressure-dependent, enhanced natriuretic response to low-dose, atrial natriuretic peptide infusion in essential hypertension.

OBJECTIVE: To examine whether the effect of atrial natriuretic peptide (ANP) on renal glomerular and tubular segmental handling of sodium in patients with essential hypertension is pressure dependent. DESIGN: Part 1. The renal effects of a low-dose continuous infusion (10 ng kg-1 min-1) with ANP for 1 h were compared in 10 untreated essential hypertensives (EH) and 13 normotensive control subjects (CS). Part 2. The hypertensives were studied on another day with ANP infusion during preceding acute BP reduction with sodium nitroprusside infusion (NP). The results were compared with those obtained during infusion with ANP+placebo (Part 1). METHODS: Lithium clearance was used to estimate the proximal tubular reabsorption of sodium. RESULTS: Part 1. Atrial natriuretic peptide caused an exaggerated increase in urinary sodium excretion (+102 vs. +38%: P < 0.05), fractional excretion of sodium (+80 vs. +37%: P < 0.05), and urinary output (+56 vs. +8.3%; P < 0.05) in EH compared with CS. Glomerular filtration rate and filtration fraction increased to the same degree in both groups. Absolute lithium clearance (CLi) increased and FELi tended to increase (P = 0.061) in EH, but these were unchanged in CS. The increase in plasma cyclic guanosine 5'-phosphate (cGMP) and urinary excretion of cGMP and the decrease in plasma aldosterone during ANP infusion were the same in the two groups. Part 2. During NP infusion the natriuresis caused by ANP in EH was reduced (+51 vs. +99%; P < 0.05). The relative changes in GFR, CLi, and FELi during ANP infusion were not affected by the preceding BP reduction with NP. Mean arterial pressure was reduced from 122 to 101 mmHg during NP infusion. The relative increase in sodium excretion in EH was significantly correlated to mean arterial pressure. CONCLUSIONS: Low-dose ANP infusion causes an exaggerated natriuresis in untreated essential hypertensives due to a more pronounced reduction in tubular reabsorption. After BP reduction, the natriuresis induced by ANP in essential hypertensives is decreased, probably due to a less pronounced reduction in tubular reabsorption beyond the proximal tubules. We suggest that the enhanced natriuretic response to ANP in EH in secondary in some degree to the elevated systemic pressure.

Adult↗
PubMed1994

Effects of captopril on renal function in healthy uninephrectomized subjects and in healthy control subjects.

OBJECTIVES: To study the importance of the renin-angiotensin-II system for renal haemodynamics and sodium and water handling in the adapted remnant kidney in healthy uninephrectomized subjects. DESIGN: Case-control study. SETTING: All subjects were investigated at laboratory C, Department of Medicine and Nephrology, Skejby Hospital. SUBJECTS: Fourteen healthy uninephrectomized (Unx) and 14 matched healthy control subjects (Cs). INTERVENTION: Captopril, 25 mg orally. MAIN OUTCOME MEASURES: The glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion clearance technique using 125I-iothalamate and 131I-hippuran as reference substances, tubular function was evaluated by the lithium clearance technique (CLi), urinary flow rate (V), sodium excretion (UNaV), fractional sodium excretion (FENa), mean blood pressure (MBP) and heart rate (HR) were measured by conventional methods and plasma levels of angiotensin II (Ang-II), aldosterone (Aldo), arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) were measured by radioimmunoassay. RESULTS: In both groups captopril ingestion resulted in a significant decrease in the MBP (Unx: 87.1 to 83.5 and Cs: 86.8 to 83.8 mmHg, median values), filtration fraction (Unx: 24.6 to 22.1 and Cs: 24.1 to 22.5%, median values) and Ang-II (Unx: 10.5 to 7.7 and Cs: 12 to 7.6 pmol-1, median values). Single kidney GFR, V, and CLi were unchanged in both groups. FENa and single kidney RPF were significantly increased in only the Cs group; FENa (Unx: 1.81 to 1.91 and Cs: 1.56 and 1.90%, median values). The plasma level of ANP was significantly decreased in only the Unx group. CONCLUSION: The data suggest that sodium handling in the remnant kidney in uninephrectomized subjects could be less sensitive to Ang-II than in healthy control subjects, and that this might be as a result of adaptive changes in the distal parts of the nephron.

Adult↗