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Biomedical subjects

H A Koomans

Publications and source records attributed to H A Koomans.

At least 73 records · Page 4Linked to original sources
PubMed1998

Evidence for increased synthesis of lipoprotein(a) in the nephrotic syndrome.

In patients with the nephrotic syndrome, markedly increased levels of lipoprotein(a) (Lp(a)) concentration have been frequently reported, and it has been suggested that this may contribute to the increased cardiovascular risk in these patients. The mechanism, however, is not clear. In the present study, in vivo fractional synthesis rate of Lp(a) was measured using incorporation of the stable isotope 13C valine. Under steady-state conditions, fractional synthesis rate equals fractional catabolic rate (FCR). FCR of Lp(a) was estimated in five patients with the nephrotic syndrome and compared with five control subjects. The mean plasma Lp(a) concentration in the patients (1749+/-612 mg/L) was higher than in control subjects (553+/-96 mg/L). Two patients were heterozygous for apolipoprotein(a) (range, 19 to 30 kringle IV domains), whereas all control subjects were each homozygous with regard to apolipoprotein(a) phenotype (range, 18 to 28 kringle IV domains). The FCR of Lp(a) was comparable between control subjects (0.072+/-0.032 pools/d) and patients (0.064+/-0.029 pools/d) despite the wide variance in plasma concentration. This suggests that differences in Lp(a) levels are caused by differences in synthesis rate. Indeed, the absolute synthetic rate of Lp(a) correlated directly with plasma Lp(a) concentration (P < 0.0001) in all subjects. The present results demonstrate that increased synthesis, rather than decreased catabolism, causes elevated plasma Lp(a) concentrations in the nephrotic syndrome.

Adult↗
PubMed1998

Nitric oxide release as an essential mitigating step in tubuloglomerular feedback: observations during intrarenal nitric oxide clamp.

Nitric oxide synthase inhibition in the kidney enhances tubuloglomerular feedback (TGF) responsiveness. This may reflect either the effect of reduced basal nitric oxide (NO) availability or the effect of impaired NO release that is physiologically induced by TGF activation. However, it is unknown whether the latter actually takes place. In this study, it was hypothesized that NO is released (from macula densa cells or endothelium) as part of the normal TGF loop, and mitigates the TGF response. In Sprague Dawley rats, TGF responsiveness was assessed (fall in tubular stop flow pressure, deltaSFP, upon switching loop of Henle perfusion rates from 0 to 40 nl/min) during an intrarenal NO clamp (systemic infusion of nitro-L-arginine, 10 microg/kg per min, followed by intrarenal nitroprusside infusion adjusted to restore renal blood flow [RBF]). This maneuver was presumed to fix intrarenal NO impact at a physiologic level. To validate the approach, TGF responsiveness during an intrarenal angiotensin II (AngII) clamp (systemic infusion of enalaprilat 0.2 mg/kg per min, followed by intrarenal AngII infusion) was also studied. AngII is presumed to modulate but not mediate, TGF, thus not to increase as part of the TGF loop. In untreated animals, RBF was 7.4 +/- 0.4 ml/min, and deltaSFP was 5.7 +/- 1.6 mmHg. Nitro-L-arginine infusion alone reduced RBF to 5.3 +/- 0.5 ml/min (P < 0.05); with nitroprusside infusion, RBF was restored to 8.3 +/- 0.7 ml/min. In this condition (NO clamp), deltaSFP was markedly increased to 19.6 +/- 3.2 mmHg (P < 0.05). By contrast, deltaSFP, which was virtually abolished during enalaprilat alone (0.2 +/- 0.3 mmHg), was not significantly different from controls during AngII clamp (8.2 +/- 1.0 mmHg). These data suggest that NO may well be released upon TGF activation. By contrast, AngII is not dynamically involved in TGF activation, but may modulate the TGF response. Thus, dynamic release of NO during TGF activation mitigates the TGF response, so that it will offset the action of a primary, as yet undefined, vasoconstrictor mediator. The source of this NO, macula densa or endothelium, remains to be elucidated.

Analysis of Variance↗
PubMed1998

Interactions of cyclosporin A and amlodipine: blood cyclosporin A levels, hypertension and kidney function.

The introduction of cyclosporin A has led to improved survival of allografts in humans. However, the use of cyclosporin A is associated with an increased prevalence of hypertension in kidney transplant recipients. Renal vasoconstriction and enhancement of tubular reabsorption contribute to this hypertensive effect. Concomitant treatment with calcium channel blockers blocks or ameliorates most of these adverse effects. This paper reviews the short-term effects of the calcium channel blocker amlodipine on plasma levels of cyclosporin A and its interaction with blood pressure and kidney function.

Amlodipine↗
PubMed1997

Cold stress provokes sympathoinhibitory presyncope in healthy subjects and hemodialysis patients with low cardiac output.

BACKGROUND: Sudden hypotension in progressive hypovolemia or during hemodialysis is attributed to sudden inhibition of sympathetic activity. Critical ventricular underfilling seems responsible for this paradox, but it is unknown why the transition from sympathoactivation accompanying hypovolemia to sympathoinhibition is so abrupt. We studied whether brief fluctuation of sympathetic activity induced by cold pressor test (CPT) evokes sympathoinhibition if applied during low cardiac output. METHODS AND RESULTS: Fourteen healthy subjects underwent CPT, lower-body negative pressure (LBNP; -45 mm Hg for 60 minutes), or the combination thereof. CPT alone caused vasoconstriction and increased muscle sympathetic nerve activity, followed by uneventful relaxation. When applied during reduced cardiac output, tachycardia, and vasoconstriction induced by prior LBNP for 6 minutes, CPT again caused vasoconstriction, now followed by acute hypotension in 10 subjects, and was associated with vasorelaxation, relative bradycardia, and fall in muscle sympathetic nerve activity. Eight subjects also experienced acute LBNP-induced hypotension in the absence of CPT, but not until 17 +/- 6 minutes of LBNP. We also performed CPT before and in the final phase of hemodialysis in 8 patients. Before dialysis, the patients tolerated CPT uneventfully, but during hemodialysis, CPT provoked acute hypotension in 5 cases, showing similar withdrawal of vasoconstriction. CONCLUSIONS: This is the first study showing that brief cold stress, tolerated well in normal circulatory conditions, can provoke sudden sympathoinhibition and hypotension when applied during decreased cardiac output induced by LBNP or hemodialysis. We suggest that during conditions of a decreased cardiac output, subtle sympathetic relaxation such as follows cold stress triggers self-enhancing relaxation that cannot be controlled.

Adult↗
PubMed1997

Hypoalbuminemia causes high blood viscosity by increasing red cell lysophosphatidylcholine.

Albumin deficiency is accompanied by a reduction in red cell deformability and blood hyperviscosity. Albumin deficiency increases plasma fibrinogen and triglyceride levels and may alter red cell membrane lipid composition. These options, which could all contribute to reduced red cell deformability (RCD) and hyperviscosity, were studied in the Nagase analbuminemic rat (NAR), a mutant Sprague Dawley rat (CON), characterized by normal total protein levels, with an absolute deficiency of albumin, but elevated levels of non-albumin proteins and hyperlipidemia. Plasma protein-binding of the polar phopholipid lysophosphatidylcholine (LPC) was markedly decreased. LPC comprised only 26 +/- 1% of total plasma phospholipids as compared to 42 +/- 2% in CON. NAR red cells in CON plasma had a viscosity that was similar to CON red cells in CON plasma. Conversely, CON red cells in NAR plasma show an increased viscosity as compared to CON red cells in CON plasma. The maximum deformation index of both NAR and CON red cells was markedly decreased in NAR plasma as compared to either NAR or CON cells in CON plasma (0.04 +/- 0.03 and 0.02 +/- 0.02 vs. 0.22 +/- 0.06 and 0.15 +/- 0.04, respectively; P < 0.05). Thus, plasma composition causes hyperviscosity and reduced RCD in NAR. Fibrinogen is not responsible since red cells in serum and red cells in plasma had a similar viscosity and differences in viscosity and RCD between NAR and CON were maintained. Plasma triglycerides are also not responsible since the viscosity of red cells in serum with a 50% reduction in triglycerides was not reduced. LPC levels in red cells were increased in NAR (8.7 +/- 0.2 vs. 5.5 +/- 0.3% of total phospholipids; P < 0.01). Adding albumin to NAR blood dose-dependently decreased whole blood viscosity, despite marked increases in plasma viscosity, and increased RCD of NAR cells (from 0.04 +/- 0.03 to 0.21 +/- 0.01; P < 0.05). There was also some effect on CON RCD of similar albumin addition to CON blood (from 0.15 +/- 0.04 to 0.29 +/- 0.03; P < 0.05). Adding albumin to NAR blood reduced red cell LPC content and increased plasma LPC content in a dose-dependent fashion, whereas there were only slight effects of adding albumin to CON blood. There was a reciprocal relation between red cell LPC and the other polar phospholipids in the red cell membrane, probably indicating exchange. The maximum deformability index of either NAR or CON cells was not affected much by adding LPC to CON plasma (NAR, from 0.22 +/- 0.06 to 0.18 +/- 0.10; CON, from 0.15 +/- 0.04 to 0.12 +/- 0.05; NS), whereas adding LPC to NAR plasma caused the red cells to become rigid. Adding LPC to CON red cells in NAR plasma caused a much stronger increase in relative LPC content (from 6.6 +/- 0.7 to 10.9 +/- 0.9%; P < 0.05) than adding LPC to CON red cells in CON plasma (from 5.6 +/- 0.4 to 6.4 +/- 0.8%; NS). Thus, in the absence of albumin, LPC in red blood cells is increased. As a consequence of the latter, RCD is decreased and whole blood viscosity increased. Alterations in red cell phospholipids are far more important than increases in plasma fibrinogen or triglycerides in determining hyperviscosity of blood and reduced RCD in NAR.

Animals↗
PubMed1997

Pressure or flow recordings for the surveillance of hemodialysis grafts.

Venous pressures (VP) measured by the dialysis machine are widely used for access surveillance and have significantly improved outcomes. VP reflect the resistance in the venous outflow tract, which will rise in the presence of stenosis. Low graft flow caused by high graft resistance predicts thrombosis. In this study we investigated whether high VP coincides with low graft flow (measured by ultrasound dilution technique). Of 70 forearm bridge grafts in 42 chronic hemodialysis patients, 31 had an angiographically proven outflow stenosis. VP at 200 ml/min blood flow (VP200), total graft resistance and venous outflow resistance were higher whereas graft flow was lower in patients with venous outflow tract stenosis as compared to patients without stenosis. Diagnostic power of the tests for identifying patients with venous stenosis showed no important differences. However, arterial inflow resistance, which is not reflected in VP measurements, represented a substantial and, more importantly, a highly variable percentage of total graft resistance. As a result graft flow showed no correlation with VP measurements. In conclusion, although patients with venous outflow stenosis may be identified accurately using venous pressure assessments, graft flow measurements seem to be more suitable for selecting patients at risk for thrombosis.

Angiography↗
PubMed1997

Effects of reduced renal perfusion pressure and acute volume expansion on proximal tubule and whole kidney angiotensin II content in the rat.

In previous studies high luminal concentrations of angiotensin II (Ang II) were found in rat proximal tubules. The physiological role of intraluminal Ang II remains to be established. In the present study, we investigated whether the luminal angiotensin II concentration in the proximal tubules ([Ang II]prox) can be modulated. Micropuncture studies were performed in control rats (C, N = 8) and rats subjected to acute volume expansion (VE, N = 8) or reduced renal perfusion pressure (RRP, N = 7). Changes in [Ang II]prox were compared to changes in whole kidney Ang II content ([ANG II]kidney) and the plasma concentration ([Ang II] plasma). In C rats, [Ang II]prox was 460 +/- 48 pmol/liter (10 to 20 times lower than hitherto reported), while [Ang II]kidney and [Ang II]plasma were 369 +/- 81 pmol/kg and 90 +/- 29 pmol/liter, respectively. In agreement with previous data, VE failed to suppress [Ang II]prox (674 +/- 132 pmol/liter), while at the same time [Ang II]kidney (42 +/- 10 pmol/kg) and [Ang II]plasma (12 +/- 3 pmol/liter) were markedly suppressed. This points to dissociated regulation of [Ang II] in the renal luminal compartment on the one hand and the extraluminal renal and systemic plasma compartments on the other hand. During RRP, [Ang II]prox increased significantly to 1675 +/- 465 pmol/liter. No dissociation between the three compartments was observed in this situation, as [Ang II]kidney (969 +/- 85 pmol/kg) and [Ang II]plasma (245 +/- 72 pmol/liter) increased in parallel. In summary, we confirm that Ang II is present in proximal tubules of rat kidneys at concentrations which exceed those in plasma. Its concentration could be modulated (approximately 3.5 increase) by reduction of renal perfusion pressure but not by acute volume expansion. In the latter condition, we observed a clear dissociation from Ang II generation in the extraluminal renal compartment, as whole kidney Ang II content was markedly suppressed.

Angiotensin II↗
PubMed1997

Hyperlipidemia is secondary to proteinuria and is completely normalized by angiotensin-converting enzyme inhibition in hypertensive fawn-hooded rats.

Two substrains of the fawn-hooded (FH) rat have been developed, one of which develops progressive hypertension and proteinuria, the FHH, and one which shows little increase in blood pressure and no renal damage, the FHL. Other hypertensive rodent models show primary metabolic disturbances before the development of renal damage, notably hypertriglyceridemia, which may also contribute to progression of renal disease. In this study we evaluated whether hyperlipidemia is a primary disturbance in FHH, or only occurs secondary to proteinuria. Lipid levels were determined before and after development of proteinuria, and compared to those found in age-matched FHL. We also determined whether reducing proteinuria with lisinopril would normalize lipid levels in aging FHH. At 4 weeks of age, proteinuria was very low (2-3 mg/day) in both FHH and FHL. While proteinuria increased steadily in aging FHH, reaching 350 +/- 62 mg/day at 40 weeks, much less increase was observed in FHL over the same period (32 +/- 5 mg/day at 40 weeks). Blood pressure was markedly higher in adult FHH than in FHL (158 +/- 2 vs. 129 +/- 2 mm Hg, p < 0.01). In 4-week-old FHL and FHH, plasma cholesterol levels were similar. Subsequently, cholesterol increased in FHH, reaching 3.4 +/- 0.9 mmol/l at 40 weeks, whereas cholesterol was barely affected by aging in FHL (2.1 +/- 0.2 mmol/l at 40 weeks). At 4 weeks, triglyceride levels were lowest in FHH. Subsequently, triglycerides increased in FHH, reaching 3.5 +/- 1.5 mmol/l at 40 weeks, as compared to 1.3 +/- 0.2 mmol/l in FHL. Besides a transient increase in triglyerides in lisinopril-treated FHH at 11 weeks, increments in blood pressure, proteinuria, cholesterol, triglycerides and apolipoproteins A-I, B and E aging FHH were effectively prevented by lisinopril. These data strongly suggest that there is no primary difference in lipid metabolism between FHH and FHL and that changes in plasma lipids in FHH as compared to FHL are all secondary to proteinuria.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Cyclosporin A increases nitric oxide activity in vivo.

The use of cyclosporine is complicated by its vaso-constrictive actions. In vitro cyclosporine has been associated with both decreased endothelium-dependent vasodilatation and increased nitric oxide activity. We studied the interaction between cyclosporine and endothelium-derived nitric oxide in seven healthy volunteers. Using venous-occlusion plethysmography, we measured forearm blood flow during intra-arterial infusion of serotonin, which in the concentrations used is a selective agonist of endothelial nitric oxide release, or NG-monomethyl-L-arginine, a specific inhibitor of nitric oxide synthase, during coinfusion of saline or cyclosporine (75 micrograms/min), respectively. During coinfusion of cyclosporine, forearm blood flow increased on maximal serotonin infusion from 2.9 (SE, 0.2) to 8.1 (0.9) mL/100 mL per minute in forearm tissue, which was significantly higher than the increase during saline coinfusion (3.0[0.3] to 6.0 [0.5]; P < .05). Cyclosporine infusion during a "free" nitric oxide system had no effect on basal forearm blood flow, but in significantly decreased forearm blood flow (21.7[2.8]%; P < .05) during fixed nitric oxide activity. These data suggest that acute administration of cyclosporine enhances both basal and receptor-stimulated nitric oxide activity. The mechanism is not clear but may include cyclosporine-induced shear stress as well as direct effects of cyclosporine. The latter was supported by our observation that gene expression of the enzyme nitric oxide synthase III was enhanced by approximately 50% after coincubation with cyclosporine. In conclusion, the present observation demonstrates that nitric oxide constitutes an important regulating mechanism that protects against cyclosporine-associated vasoconstriction in vivo.

Adult↗
PubMed1997

Nifedipine attenuates systemic and renal vasoconstriction during nitric oxide inhibition in humans.

Clinical states associated with nitric oxide deficiency are often accompanied by vasoconstriction. We studied the effects of prolonged infusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on systemic and renal hemodynamics in humans and the reversibility of the established vasoconstriction by calcium channel blockade with nifedipine. Seven healthy men underwent three 7-hour clearance studies. During one study, L-NMMA (3 mg/kg priming dose plus 3 mg.kg-1.h-1) was infused during hours 2 through 5, and during another study, nifedipine (0.015 mg/kg priming dose plus 0.015 mg.kg-1.h-1) was coinfused during hours 4 and 5. A third study served as time control. L-NMMA elicited reproducible systemic and renal vasoconstriction that was stable during the 4 hours of infusion. Systemic vascular resistance index, calculated from bioimpedance-derived cardiac index, increased from 22 +/- 1 to 29 +/- 2 mm Hg.min.m2.L-1 (P < .05). Mean arterial pressure rose by 4 +/- 1 mm Hg (P < .05), and heart rate, stroke index, and cardiac index decreased. Renal blood flow, calculated from renal plasma flow, decreased from 1182 +/- 101 to 785 +/- 53 mL/min, and renal vascular resistance increased from 73 +/- 5 to 115 +/- 6 mm Hg.min.L-1 (P < .05). Glomerular filtration rate decreased from 114 +/- 6 to 104 +/- 6 mL/min (P < .05), and filtration fraction increased. Sodium excretion fell from 89 +/- 9 to 32 +/- 7 mumol/min (P < .05). Nifedipine completely reversed systemic vasoconstriction. Nifedipine caused partial restoration of renal vascular resistance and complete normalization of glomerular filtration rate and sodium excretion but left the elevated filtration fraction unaltered. We conclude that sustained nitric oxide deficiency in humans is accompanied by strong systemic and renal vasoconstriction, decreased glomerular filtration rate, and sodium retention. Nifedipine can reverse most of these effects, suggesting a role for calcium channel blockade in pathological states of impaired nitric oxide activity.

Adult↗
PubMed1997

Endothelin-1-induced vasopressor responses in essential hypertension.

The potential role of endothelin-1 (ET-1) in essential hypertension in humans is still subject to debate. We recently reported strong sodium retention and renal vasoconstriction during pathophysiological increments in plasma ET-1. Apart from this vasoconstrictor action, ET-1 also has mitogenic properties that play a role in the pathophysiology of hypertension. On the other hand, some data refute an important role of ET-1 in hypertension. We therefore investigated in nine subjects with essential hypertension the constrictor actions of ET-1 by challenging these subjects with a systemic infusion of ET-1 (0.5 ng/kg per minute for 60 minutes, then 1.0 ng/kg per minute for 60 minutes, and finally 2.0 ng/kg per minute for 60 minutes). Furthermore, we studied whether these effects of ET-1 could be modulated by oral use of the angiotensin-converting enzyme inhibitor enalapril (20 mg BID) or the calcium channel blocker nifedipine (60 mg OD). ET-1 infusion increased plasma ET-1 levels from 2.5+/-0.4 to 11.6+/-1.0 pmol/L (P<.05). Blood pressure rose by approximately 10 mm Hg (P<.05). Cardiac index decreased by 21+/-22%, whereas calculated systemic vascular resistance increased by 27+/-6% (P<.05). Renal blood flow decreased from 1051+/-94 to 707+/-60 mL/min at the end of the ET-1 infusion (P<.05), and calculated renal vascular resistance increased from 118+/-19 to 189+/-19 mm Hg x min/L (P<.05). Sodium excretion decreased from 227+/-39 to 111+/-15 micromol/min (P<.05). Both enalapril and nifedipine treatment prevented the systemic effects of ET-1 infusion in these subjects. However, during enalapril treatment, despite renal predilatation, ET-1 reduced renal blood flow (from 1119+/-132 to 701+/-75 mL/min, P<.05) and increased renal vascular resistance (from 111+/-16 to 187+/-28 mm Hg x min/L, P<.05) to the same levels as during ET-1 infusion alone. Nifedipine pretreatment attenuated the ET-1-induced fall in renal blood flow (from 1088+/-93 to 907+/-68 mL/min) and increase in renal vascular resistance (from 105+/-9 to 133+/-10 mm Hg x min/L). Although neither drug modulated the antinatriuretic effect of ET-1, nifedipine increased basal sodium excretion (P<.05), which compensated for the decrease during ET-1 infusion. In conclusion, essential hypertensive subjects are sensitive to the vasoconstrictor effects of ET-1. Both enalapril and nifedipine can prevent the systemic effects of ET-1, but nifedipine seems more effective in attenuating the renal constrictor effects of ET-1.

Adult↗
PubMed1997

Estrogen replacement during hypoalbuminemia may enhance atherosclerotic risk.

Estrogen replacement therapy is considered antiatherosclerotic because it reduces LDL cholesterol and fibrinogen and increases HDL cholesterol concentrations. However, exogenous estrogen is also known to increase hepatic triglyceride production. Hyperlipidemia in the nephrotic syndrome is probably due to increased lipoprotein secretion into plasma and decreased clearance of lipoprotein cholesterol and triglycerides. Previously, lipid-lowering effects of ovariectomy in analbuminemic rats were observed, suggesting that in the presence of hypoalbuminemia, estrogen replacement may have adverse effects on the lipid profile. To test this hypothesis, ovariectomized control rats and rats with Adriamycin-induced nephrotic syndrome were treated with estradiol. In ovariectomized controls, estradiol reduced plasma LDL cholesterol, apolipoprotein B, and fibrinogen and increased apolipoprotein A-I and triglycerides. Nephrotic rats were characterized by a marked decrease in plasma colloid osmotic pressure, hyperfibrinogenemia, hyperlipidemia, and stimulated hepatic fatty acid synthesis. The beneficial effects of estradiol on LDL cholesterol, apolipoprotein B, and fibrinogen found in ovariectomized controls were not present in estradiol-treated nephrotic rats. This suggests that in hypoalbuminemia, downregulation of the LDL receptor overrides putative estradiol-induced increases in LDL receptor activity. Moreover, estrogen replacement in the nephrotic syndrome doubled fatty acid synthesis and triglyceride secretion, and markedly exacerbated hypertriglyceridemia, suggesting saturation of triglyceride clearance. Thus, severe hypoalbuminemia in rats induces an atherosclerotic metabolic response that is aggravated by estrogen replacement. These findings suggest that estrogen replacement in hypoalbuminemic subjects could be contra-indicated.

Animals↗
PubMed1997

Role of endothelin receptor subtypes in the systemic and renal responses to endothelin-1 in humans.

The authors recently reported that infusion of endothelin-1 in humans to obtain pathophysiological plasma levels causes profound renal vasoconstriction and sodium retention. The relative roles of the ETA- and ETB-receptor subtypes in these effects in humans is unknown. Such information is essential in view of the recent introduction of endothelin-receptor blockers in clinical medicine. The study presented here was designed to define the role of the ETA- and ETB-receptor subtypes in the renal actions of endothelin-1 in humans. Systemic infusion of endothelin-1, a nonselective receptor agonist, was compared with infusion of equimolar dosages of the ETB-selective agonist endothelin-3 in healthy volunteers. Endothelin-1 infusion was associated with an approximate 2.5-fold increase in plasma levels of endothelin-1. This was accompanied by an increase in blood pressure by approximately 6 mm Hg (P < 0.05). During endothelin-1 infusion, RPF decreased from 642 +/- 42 to 480 +/- 36 mL/min (P < 0.05) and GFR from 121 +/- 4 to 109 +/- 7 mL/min (P < 0.05). Sodium excretion rate decreased during endothelin-1 infusion, from a baseline value of 182 +/- 33 to 84 +/- 28 mumol/min at the end of the endothelin-1 infusion. Endothelin-3 infusion also resulted in a approximate 2.5-fold increase of plasma levels of endothelin-3. However, in contrast to the endothelin-1 infusion, endothelin-3 had no effect on blood pressure, renal hemodynamics, and electrolyte excretion. These results suggest that the systemic and renal vasoconstrictor effects of endothelin-1 in humans are predominantly mediated by the ETA receptors.

Adult↗
PubMed1997

Angiotensin-converting enzyme inhibition in the prevention and treatment of chronic renal damage in the hypertensive fawn-hooded rat.

The spontaneously hypertensive fawn-hooded rat (FHH) develops accelerated albuminuria and focal glomerular sclerosis (FGS), leading to ESRD and shortening of lifespan. The FHH is characterized by moderate systemic hypertension, a relatively low afferent to efferent arteriolar resistance ratio, and glomerular hypertension. The FHH study presented here was designed to examine the efficacy of early-onset, late-onset, or early-temporary angiotensin I-converting enzyme inhibition (ACE-i) in ameliorating long-term hypertension and FGS, and improving survival, as well as to relate its protective efficacy to preexistent FGS and to reduction of glomerular pressure (PGC) Untreated rats developed hypertension and high PGC, and all (N = 22) except one died of ESRD within the 72-wk follow-up period. Early-onset (at 7 wk of age) ACE-i prevented development of systemic and glomerular hypertension, and it largely prevented proteinuria and FGS; all rats survived throughout the follow-up period. Rats treated with late-onset (22 wk) ACE-i were hypertensive and proteinuric at the start of ACE-i, and they showed beginning FGS. ACE-i corrected the hypertension, albuminuria, and PGC but could not fully prevent some hypertension, albuminuria, and FGS at the later stage. Early-temporary (7 to 22 wk) ACE-i adequately controlled blood pressure and development of FGS during therapy, but after withdrawal of ACE-i, systemic and glomerular hypertension developed as in untreated animals. This regimen postponed but did not control FGS development and early mortality. The results of this study indicate that: (1) early-onset ACE-i very effectively protects against development of renal damage in the FHH; (2) this protection is associated with normalization of the elevated glomerular capillary pressure; (3) ACE-i cannot completely prevent further development of previously established FGS, despite lowering glomerular capillary pressure; (4) early-temporary ACE-i has no long-term controlling effect on arterial and glomerular pressure, and it cannot control development of FGS.

Age Factors↗
PubMed1997

Pulmonary embolism after thrombolysis of hemodialysis grafts.

The aim of this study was to determine the incidence of pulmonary embolization occurring after mechanical or pharmacomechanical percutaneous intravascular thrombolysis in 23 patients with occluded hemodialysis grafts. In all patients, pulmonary perfusion scintigraphy was performed before and immediately after thrombolysis. In eight (35%) of the patients, there was evidence of pulmonary embolism resulting from the interventional procedure; however, in only one was there clinical symptoms. It is concluded that there is substantial risk of pulmonary embolism in patients undergoing percutaneous intravascular thrombolysis for an occluded hemodialysis graft.

Catheters, Indwelling↗