Safety and transcervical endometrial resection.
Explore the source record for details and available documents.
Absorption↗
Biomedical subjects
H A Koomans
Publications and source records attributed to H A Koomans.
Ovariectomy decreases plasma triglyceride levels in analbuminaemic rats by lowering hepatic triglyceride secretion.
In mutant analbuminaemic rats (NAR), females demonstrate a more marked hypertriglyceridaemia than males. Ovariectomy decreases triglyceride levels in female NAR. We measured triglyceride secretion rates in vivo as well as the activity of acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS) in hepatic cytosol obtained from female control Sprague-Dawley (SD) rats and NAR with or without ovariectomy. NAR were severely hyperlipidaemic, and triglyceride, cholesterol, apolipoprotein A-I and plasma protein concentrations levels were decreased (all P < 0.01) by ovariectomy. Only triglyceride levels were decreased by ovariectomy in the SD rats (P < 0.05). Oestradiol treatment in ovariectomized NAR restored plasma protein and triglyceride concentrations to levels similar to those observed in intact female NAR and caused a marked increase in plasma cholesterol. Ovariectomy in NAR reduced lipoprotein triglycerides and cholesterol in VLDL, IDL and LDL1, but had little effect on the triglyceride-cholesterol ratio of these particles. Both ACC and FAS activities were markedly increased in NAR vs. SD rats (P < 0.01). This increase was partially corrected by ovariectomy. There was no significant effect of ovariectomy on ACC or FAS activity in the SD rats. Triglyceride secretion rates were significantly increased in NAR vs. SD rats (135 +/- 10 vs. 103 +/- 12 nmol/min per 100 g body weight; P < 0.05). Ovariectomy markedly decreased triglyceride secretion rate in NAR to 69 +/- 6 (P < 0.01), but not in SD rats (92 +/- 8 nmol/min per 100 g body weight, NS). Oestradiol treatment in ovariectomized SD rats restored triglyceride levels but had no significant effect on triglyceride secretion rate (106 +/- 23 nmol/min per 100 g).(ABSTRACT TRUNCATED AT 250 WORDS)
Acetyl-CoA Carboxylase↗
Evaluation of the lithium clearance method: direct analysis of tubular lithium handling by micropuncture.
Explore the source record for details and available documents.
Animals↗
Reabsorption of nitro-L-arginine infused into the late proximal tubule participates in modulation of TGF responsiveness.
Previous studies indicate that endothelium-derived nitric oxide (NO) can directly modulate afferent arteriolar tone and that macula densa-derived NO can indirectly regulate afferent arteriolar tone by modulating the tubuloglomerular feedback (TGF) mechanism. The present in vivo micropuncture study evaluated whether the effect of late proximal tubular perfusion with the nitric oxide synthase (NOS) inhibitor, NG-L-arginine (NLA), on TGF responsiveness is related to reabsorption of NLA. Late proximal perfusion of 10(-3) M NLA resulted in a gradual, time-dependent enhancement of maximum TGF-mediated decreases in stop-flow pressure (SFP) from -7.1 +/- 0.7 to -19.4 +/- 1.6 mm Hg (P < 0.01). A detailed recording of SFP revealed that the maximum response during late proximal perfusion of NLA was obtained eight to nine minutes following the initiation of the perfusion, whereas maximum TGF responses evoked by late proximal perfusion with ATF were reached within one to two minutes. NLA infused into the late proximal segment of a neighboring nephron also resulted in enhancement of maximum SFP feedback responses from -5.5 +/- 0.5 to -10.4 +/- 1.9 mm Hg (P < 0.05), indicating that NLA can be reabsorbed and can consequently influence TGF responses. Finally, maximum SFP feedback responses were obtained prior to and following late proximal perfusion of 10(-3) M NLA dissolved in ATF, 10(-3) M NLA dissolved in 285 mM mannitol, and following perfusion with mannitol without NLA.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
Impaired endothelial function in patients with nephrotic range proteinuria.
Proteinuria is associated with increased cardiovascular morbidity and mortality. Release of nitric oxide by the endothelium has been advanced as an important defense mechanism against vessel-wall damage. In the present study we therefore tested the hypothesis that proteinuria is associated with a defect in nitric oxide-dependent vasodilation, by using venous occlusion plethysmography of the forearm in nine patients with nephrotic range proteinuria (> 3.5 g/24 hr) and normal renal function (creatinine 83.1 +/- 8.7 mumol/liter), eight patients with active glomerulonephritis but normal renal function (creatinine 81.2 +/- 5.4 mumol/liter) and low range proteinuria (< 1.0 g/24 hr), and ten healthy volunteers. We infused L-NMMA (2 mg/min) to inhibit basal nitric oxide production, serotonin (0.1, 0.3 and 1.0 ng/kg/min) as an endothelium-dependent vasodilator, and nitroprusside (1, 10, 30 and 100 ng/kg/min) as an endothelium-independent vasodilator into the brachial artery. Administration of L-NMMA decreased basal forearm vascular resistance (FVR) by 30 +/- 4% in the nephrotic subjects, 38 +/- 4% in the non-nephrotic patients and by 37 +/- 2% in the healthy controls (P = 0.15). Upon the highest dose of serotonin FVR decreased in nephrotic subjects by 40 +/- 5%, which was less than in non-nephrotic patients (56 +/- 3%; P < 0.05) or in healthy controls (55 +/- 3%; P < 0.05). The maximal decrease in FVR upon nitroprusside infusion was not different between the groups (respectively 84 +/- 2, 84 +/- 3 and 84 +/- 2%). The impaired serotonin-induced vasodilation could be attributed to a defect in nitric oxide production, since L-NMMA almost completely prevented serotonergic vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Efficacy of intrarenal ACE-inhibition estimated from the renal response to angiotensin I and II in humans.
Recent studies on the nature of the renin-angiotensin system (RAS) in animals have led to the concept that systemic and intrarenal RAS can be influenced to different degrees by angiotensin converting enzyme (ACE) inhibitors. Assessment of efficacy of intrarenal ACE inhibition by ACE inhibitors in humans is necessarily indirect and has not been reported. We therefore monitored the renal response to acute angiotensin (Ang) I infusion in volunteers taking 20 mg enalapril twice daily, and related the responses to the obtained increments in plasma Ang II levels. Ang I infusion rates of 4, 8, 16, and 32 pmol/kg/min caused gradual increments in plasma Ang I (maximal change from 26 +/- 18 to 578 +/- 120 pmol/liter, P < 0.05) and, despite treatment with enalapril, also of Ang II (from 3 +/- 1 to 29 +/- 5 pmol/liter, P < 0.05). This was associated with large reductions in renal plasma flow (paraaminohippurate clearance), filtration fraction, maximal urine flow, sodium excretion, lithium and uric acid clearance, and increments in mean arterial pressure and plasma aldosterone (P < 0.05 for each variable). Strong correlations existed between the changes in either variable and the increment in plasma Ang II. Infusions of Ang II at 1 and 4 pmol/kg/min in the same subjects caused comparable increments in plasma Ang II and had similar physiological effects as found during the Ang I infusion. Analysis of covariance of the changes in plasma Ang II and each of the measured variables revealed no differences between Ang I and Ang II infusions.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Naloxone inhibits renal hemodynamic effect of head-out water immersion in humans.
Head-out water immersion (HOI) is followed by renal vasodilation and natriuresis, in association with a fall in blood pressure. The latter suggests an exaggerated sympathetic suppression. We studied the role of endogenous opioids on the renal response to HOI. Six healthy subjects underwent four- hour clearance studies during: (1) time control; (2) naloxone 0.1 mg/kg i.v. bolus, followed by 0.1 mg/kg/hr; (3) HOI; and (4) concomitant HOI and naloxone administration. Compared to the time control study, naloxone had no effects on mean arterial pressure (MAP), plasma renin activity (PRA), aldosterone, catecholamines, atrial natriuretic peptide (ANP), glomerular filtration rate (GFR), estimated renal plasma flow (ERPF), and sodium excretion. HOI caused significant decrements of MAP, PRA, aldosterone, and catecholamines, and increased ANP, GFR, from 94 +/- 5 to 102 +/- 5 ml/min (P < 0.01), ERPF, from 529 +/- 30 to 616 +/- 35 ml/min (P < 0.01), and sodium excretion. Renal blood flow increased as well, and calculated renal vascular resistance decreased from 99 +/- 6 to 77 +/- 5 mm Hg.min.liter-1 (P < 0.01). HOI during concomitant naloxone administration had similar effects on MAP and humoral factors, however, caused no change in GFR, ERPF and renal blood flow, and the fall in renal vascular resistance, from 98 +/- 6 to 83 +/- 5 mm Hg.min.liter-1 (P < 0.05) was significantly less than found in the absence of naloxone (P < 0.05). The natriuretic effect was undisturbed. These data suggest that endogenous opioids play a role in the response to HOI, in particular, potentiate the renal vasodilatory response.
Adult↗
Nitric oxide antagonizes the actions of angiotensin II to enhance tubuloglomerular feedback responsiveness.
The present study was designed to investigate whether nitric oxide (NO) antagonizes angiotensin II (Ang II) in modulating the tubuloglomerular feedback (TGF) system. Maximum TGF responses were assessed by evaluating stop-flow pressure (SFP) responses to late proximal perfusion with artificial tubular fluid (40 nl/min). Peritubular capillary (PTC) infusion of 10(-3) M NG-L-arginine (NLA) at a rate of 20 nl/min, and infusion of 10(-7) and 10(-6) M Ang II at rates that did not decrease SFP under conditions of zero flow to the macula densa (resting SFP), augmented maximum SFP feedback responses to 12.0 +/- 1.7, 12.1 +/- 2.4 and 16.9 +/- 3.0 mm Hg, respectively (all P < 0.01 vs. control response). Combined PTC infusion of NLA and 10(-7) M Ang II at a rate of 20 nl/min resulted in decreases in resting SFP in 7 of the 12 nephrons studied. When the infusion rate was decreased to 15 +/- 3 nl/min, concomitant PTC infusion of NLA and 10(-7) M Ang II was associated with a tremendous increase in maximum TGF responses (23.8 +/- 3.9 mm Hg; P < 0.01 vs. responses during PTC NLA or Ang II) in the absence of a decrease in resting SFP. During AT1 receptor blockade using losartan, SFP feedback responses were attenuated to 1.6 +/- 0.6 mm Hg and PTC infusion of NLA only augmented TGF responses to 3.8 +/- 1.0 mm Hg. These results strongly suggest that local NO antagonizes Ang II with respect to the regulation of TGF responsiveness. Disruption of this balance by NO synthesis inhibition strongly potentiates TGF-independent and TGF-dependent actions of Ang II on the preglomerular vasculature.
Angiotensin II↗
Proteinuria, lipoproteins and renal apolipoprotein deposits in uninephrectomized female analbuminemic rats.
To elucidate the pathogenetic role of hyperlipidemia per se in the development of glomerulosclerosis, severely hyperlipidemic female analbuminemic rats (NAR) and mildly hyperlipidemic male NAR were studied for a period of 37 weeks after uninephrectomy (UNX). Plasma cholesterol increased from 6.3 +/- 0.4 (week 4) to 11.9 +/- 0.6 mmol/liter (week 37) in the female NAR, and from 4.3 +/- 0.1 to 6.4 +/- 0.5 mmol/liter in the male NAR in the same period. Plasma protein concentration was also consistently higher in female NAR (60 +/- 1 g/liter) as compared to male NAR (52 +/- 1 g/liter). Plasma viscosity was higher in female NAR than in male NAR, but there were no differences in blood viscosity. Proteinuria increased progressively in the UNX female NAR from 25 weeks after surgery, reaching a final value of 141 +/- 37 mg/day. No proteinuria occurred in the UNX male NAR (final value 15 +/- 2 mg/day). Glomerular capillary pressure, measured prior to the onset of proteinuria, was not significantly different in UNX female NAR and UNX male NAR. At the end of the study glomerulosclerosis and lipid deposition was only found in the UNX female NAR. Throughout the study hyperfiltration and hyperperfusion, relative to the one-kidney clearances of the sham-operated (2K) animals, were not different in UNX male and female NAR. No differences were observed in blood pressure. Hypertrophy, evaluated by glomerular diameters, was less pronounced in UNX female NAR (174 +/- 3 microns) than in UNX male NAR (190 +/- 7 microns). Glomerular diameters in 2K female and male NAR were similar (respectively 158 +/- 2 and 157 +/- 4 microns). Plasma apo B levels were similar (2K female NAR: 204 +/- 8 U; 2K male NAR 204 +/- 13 U), but cholesterol and triglyceride content of apo B-containing lipoproteins, namely VLDL, IDL and LDL, was increased twofold in the female NAR as compared to the male NAR, implying a larger particle size in the female NAR. Deposition of apo B and apo E was observed in the glomerular mesangium of UNX female NAR, particularly in sclerotic lesions. Glomerular apo A-I deposits were localized primarily in visceral epithelial cells and were not associated with sclerotic lesions. The development of proteinuria and glomerulosclerosis after UNX in female NAR but not in male NAR may depend upon differences in plasma lipoprotein composition, but is apparently not related to differences in whole kidney hyperfiltration and hyperperfusion, glomerular capillary pressure, or blood viscosity.
Animals↗
Plasma triglyceride levels are higher in nephrotic than in analbuminemic rats despite a similar increase in hepatic triglyceride secretion.
The relative contributions of increased hepatic secretion of triglyceride (TG) and decreased TG catabolism to hypertriglyceridemia in the nephrotic syndrome, and their relationship to urinary protein loss and reduced plasma colloid osmotic pressure (pi) remain unclear. We measured the activity of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), two key enzymes of fatty acid synthesis in hepatic cytosol, in fed control rats, in rats with congenital analbuminemia (NA) that are free of proteinuria, and in rats with adriamycin-induced nephrotic syndrome (ADR). Both NA and ADR rats had decreased pi (respectively 13.2 +/- 0.3 and 10.7 +/- 0.4 mm Hg vs. control rats 18.3 +/- 0.7 mm Hg, P < 0.05), but only ADR rats had increased plasma TG (5.8 +/- 2.6 mmol/liter vs. 1.5 +/- 0.2 mmol/liter in both control and NA rats, P < 0.05), and were proteinuric: 811 +/- 45 mg/day, P < 0.01 versus control and NA rats. Total cytosolic ACC activity, expressed per g body weight, was increased in both NA and ADR rats by 45% and 39%, respectively (P < 0.05). Total FAS activity was increased by 65% and 115% in NA and ADR rats, respectively (P < 0.05). Thus low pi was consistently associated with an increase in total ACC and FAS activities in the livers of fed rats. However, low pi was consistently associated with an increase in plasma TG only in ADR rats. Hepatic TG secretion rates, measured in vivo after blocking lipolysis with Triton WR-1339 in fasting animals, were increased by 33% in both ADR and NA rats as compared to controls (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effects of low-dose angiotensin II infusion on loop segment reabsorption: a free-flow micropuncture study in rats.
1. Little direct information is available on the actions of angiotensin II beyond the proximal tubule. We therefore studied the effect of a mildly vasoconstrictive dose of angiotensin II on tubular handling of water, sodium (Na+) and lithium (Li+) in rats by means of free-flow micropuncture at the late proximal tubule and the early distal tubule. 2. Endogenous angiotensin II was suppressed by pretreatment with enalapril. Compared with a control group, angiotensin II increased mean arterial pressure by 15 mmHg. Glomerular filtration rate decreased from 1.32 +/- 0.05 to 1.10 +/- 0.05 ml/min, Na+ excretion from 0.43 +/- 0.09 to 0.13 +/- 0.03 mumol/min, fractional delivery of water at the late proximal tubule from 50.1 +/- 1.7 to 42.9 +/- 3.2%, fractional delivery of Na+ at the late proximal tubule from 46.5 +/- 1.3 to 39.1 +/- 3.5% and fractional delivery of water at the early distal tubule from 26.4 +/- 1.4 to 21.9 +/- 1.0% (P < 0.05 for each variable). Fractional delivery of Na+ at the early distal tubule did not change significantly. 3. Similar experiments were performed during partial aortic constriction to exclude the effects of increased perfusion pressure. The data obtained were similar, except that in this group the fractional delivery of Na+ at the early distal tubule decreased from 8.6 +/- 0.7 to 6.8 +/- 0.9% (P < 0.05). 4. The relation between late proximal tubule Na+ delivery and Na+ reabsorption between late proximal and early distal tubule was not disturbed by angiotensin II. For water, however, this relation tended to shift to a higher reabsorption rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorption↗
Long-term fructose versus corn starch feeding in the spontaneously hypertensive rat.
1. Fructose feeding, as opposed to vegetable starch feeding, has been shown to elevate blood pressure and to decrease insulin sensitivity in normotensive rats. The long-term relevance of this is unclear, and data in hypertensive strains are scarce. 2. We studied the effects of 27 weeks of a fructose-versus a corn-starch-enriched (69.5% w/w) diet in the spontaneously hypertensive rat. 3. In both dietary groups, blood pressure increased with ageing, with no apparent difference between the diets. The fructose-fed rats gained less weight. However, even selecting fructose-fed rats that matched the weight gain in the corn starch group, did not reveal a significant elevation of systolic blood pressure over time. 4. Extracellular fluid volume was comparable in fructose-fed and corn-starch-fed rats. No effects on creatinine clearance, proteinuria or renal histology were found. Fasting values of plasma triacylgycerols and cholesterol were increased mildly after 2 weeks on the fructose diet. However, fasting glucose and insulin measured after 2 weeks, and the response to an intraperitoneal glucose load, were no different. After 23 weeks of the diets, fasting values of plasma glucose, insulin, triacylglycerols and cholesterol did not differ. There were small differences in the response of plasma glucose levels to the intraperitoneal glucose load, but the area under the curve was not different. The baseline insulin resistance present in spontaneously hypertensive rats possibly blunts the metabolic response to dietary fructose. 5. After 27 weeks, the diets were switched in cross-over design, and measurements were continued until 39 weeks. The fructose diet did not elevate systolic blood pressure in this follow-up experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Direct assessment of extracellular water volume by the bromide-dilution method in growth hormone-deficient adults.
Body composition and water content were assessed in 36 growth hormone deficient (GHD) patients (M:23, F:13) and 14 controls (M:7, F:7) using anthropometry, hydrodensitometry, bioelectrical impedance measurement and the bromide-dilution method, with which extracellular water volume can be measured directly. GHD patients, compared to controls, did not differ in extracellular water volume, in hydration state and water distribution. A higher BMI (P = 0.002) and a higher body fat mass (P < 0.0001) were found in the patients. Based on circumference measurements, the GHD patients had a higher waist/hip ratio (P = 0.0001). This study shows that GHD patients, in comparison with healthy controls, have a normal extracellular water volume. The finding that extracellular water volume is within the normal range in GHD patients may be clinically relevant as it is well known that in the first months after initiating GH-replacement therapy, most patients have signs and symptoms of excessive water retention.
Adult↗
Analysis of lithium in renal tubular fluid by atomic absorption spectrometry with use of tantalum foil.
Explore the source record for details and available documents.
Animals↗
Understanding the nephrotic syndrome: what's new in a decade?
Explore the source record for details and available documents.
Animals↗
Hypertension after renal transplantation. Calcium channel or converting enzyme blockade?
We compared the effects of 4 weeks of calcium channel blockade (amlodipine) or converting enzyme inhibition (lisinopril) on blood pressure and renal hemodynamics in a double-blind crossover trial in a group of 20 hypertensive cyclosporine-treated renal transplant patients. Amlodipine (10 mg) was more effective than the same dose of lisinopril in controlling hypertension (mean 24-hour arterial pressure, 111 +/- 9 and 115 +/- 9 mm Hg, respectively; P < .05). Blood pressure during both treatments was lower than during placebo (124 +/- 12 mm Hg, P < .05). Compared with placebo, amlodipine treatment was associated with a significant increase in glomerular filtration rate (10 +/- 20%, P < .05) and effective renal plasma flow (27 +/- 20%, P < .01) and a decrease in renal vascular resistance (23 +/- 18%, P < .01). Renal hemodynamics did not change during lisinopril. Neither drug had an effect on proteinuria. The data indicate that amlodipine is more effective than lisinopril in controlling hypertension in cyclosporine-treated patients and that treatment with amlodipine but not with lisinopril is accompanied by an increase in glomerular filtration rate and effective renal plasma flow and a decrease in renal vascular resistance. The data suggest that the renin-angiotensin system does not play a main role in determining cyclosporine-associated changes in renal hemodynamics and has a limited role in determining cyclosporine-associated hypertension.
Adult↗
Effectiveness of enalapril versus nifedipine to antagonize blood pressure and the renal response to endothelin in humans.
Endothelin-1 infusion into humans to obtain pathophysiological plasma levels causes mild hypertension, strong renal vasoconstriction, and sodium retention. We studied whether oral use of the angiotensin-converting enzyme inhibitor enalapril (20 mg BID) or the calcium channel blocker nifedipine (60 mg OD) could attenuate these effects of endothelin-1 (2.5 ng/kg per minute for 90 minutes) in six healthy volunteers. Endothelin infusion alone increased plasma endothelin from 3.0 +/- 0.3 to 8.8 +/- 1.0 pmol/L (P < .05). Blood pressure rose by approximately 6 mm Hg (P < .05). Renal function changes were relatively large: Renal blood flow decreased from 941 +/- 76 to 729 +/- 118 mL/min (P < .05) and glomerular filtration rate from 105 +/- 9 to 92 +/- 10 mL/min (P < .05); renal vascular resistance increased from 101 +/- 7 to 152 +/- 20 mm Hg.min/L (P < .05); and sodium excretion decreased from 158 +/- 54 to 86 +/- 27 mumol/min (P < .05). Enalapril treatment reduced blood pressure from 94 +/- 2 to 87 +/- 3 mm Hg (P < .05) and prevented the hypertensive response to endothelin. By contrast, despite renal predilatation, endothelin reduced renal blood flow strongly (from 1063 +/- 127 to 763 +/- 100 mL/min, P < .05), although maximal renal vascular resistance was numerically lower (124 +/- 11 mm Hg.min/L) than during endothelin alone (P < .05). Glomerular filtration rate fell from 118 +/- 11 to 108 +/- 11 mL/min (P < .05). Enalapril did not alter the antinatriuretic effect of endothelin.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
L-arginine does not prevent the renal effects of endothelin in humans.
The infusion of endothelin to obtain plasma levels as present in sodium-retaining conditions such as heart failure and hepatorenal syndrome has been shown to cause sodium retention and renal vasoconstriction. Whether these renal effects of endothelin could be modulated by the stimulation of nitric oxide production by the infusion of L-arginine was examined. Therefore, the renal and endocrine effects of the systemic administration of endothelin (2.5 ng/kg per minute for 90 min), L-arginine (5 mg/kg per minute for 90 min), or the combination of endothelin and L-arginine were studied in healthy subjects under clearance conditions. During endothelin infusion, plasma endothelin levels rose from 3.0 +/- 0.2 to 14.1 +/- 2.4 pmol/L (P < 0.01). Mean arterial pressure increased by 7 mm Hg (P < 0.01). The effects on renal function were disproportionately large: renal vascular resistance increased from 77.5 +/- 3.2 to 124.1 +/- 6.7 mm Hg/min per liter (P < 0.01), and sodium excretion fell from 178 +/- 30 to 83 +/- 11 mumol/min (P < 0.01). Endothelin had no effect on urinary nitrite excretion. L-Arginine caused a fall in blood pressure of 5 mm Hg (P < 0.01) and decreased renal vascular resistance by 12% (P < 0.05). Sodium excretion increased twofold. This was associated with an increase in urinary nitrite excretion from 112 +/- 36 to 465 +/- 190 nmol/min (P < 0.01), suggesting stimulation of renal nitric oxide production. During the combination of endothelin and L-arginine, urinary nitrite excretion increased similarly.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗