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Biomedical subjects

H A Koomans

Publications and source records attributed to H A Koomans.

At least 55 records · Page 3Linked to original sources
PubMed1998

Divergent effects of ACE-inhibition and calcium channel blockade on NO-activity in systemic and renal circulation in essential hypertension.

OBJECTIVE: Nitric oxide is a vasodilating and blood pressure lowering substance. To investigate whether calcium antagonists or angiotensin-converting enzyme (ACE) inhibitors increase vascular nitric oxide activity, we assessed systemic and renal vascular sensitivity to nitric oxide synthase inhibition in hypertensives on and off medication. METHODS: Ten essential hypertensive patients, aged 22-51 years, were studied 3 times: > or = 4 weeks off medication, after 3 weeks treatment with enalapril 20 mg twice a day and after 3 weeks nifedipine 60 mg/day. Each time, 24-h blood pressure registration was performed, followed by a clearance study to obtain a 3-h dose-response curve for intravenously infused NG-monomethyl-L-arginine (L-NMMA, respectively 0.75, 1.5 and 3.0 mg/kg/h). RESULTS: L-NMMA dose-dependently increased mean arterial pressure with 5 +/- 2 mmHg and systemic vascular resistance with 24 +/- 5% at maximum dose, whereas cardiac output decreased (all P < 0.001). Enalapril and nifedipine treatment decreased blood pressure, while the L-NMMA-induced increase in systemic vascular resistance was potentiated (enalapril: 45 +/- 7% and nifedipine: 46 +/- 8%; both P < 0.01). L-NMMA also dose-dependently decreased renal blood flow by 58 +/- 8% at maximum dose (P < 0.001), but neither drug potentiated these effects. CONCLUSION: These results indicate that, in essential hypertensives, antihypertensive therapy with enalapril or nifedipine increases nitric oxide dependency of systemic vascular tone, which may play a role in the blood pressure lowering effect of these drugs. However, this phenomenon cannot be observed in the renal circulation, suggesting a different regulation of endothelium-dependent vasomotion in the hypertensive kidney.

Adult↗
PubMed1998

A comparison between PTFE and denatured homologous vein grafts for haemodialysis access: a prospective randomised multicentre trial. The SMASH Study Group. Study of Graft Materials in Access for Haemodialysis.

OBJECTIVES: To compare patency and complication rates of polytetrafluoroethylene (PTFE) grafts and denatured homologous vein (DHV) grafts for long-term haemodialysis. DESIGN: A prospective randomised multicentre trial. MATERIALS: One hundred and thirty-one patients were enrolled between September 1994 and April 1997. Sixty-three DHV grafts and 68 PTFE grafts were implanted in 60 meals and 71 females. Complications and interventions were monitored. Patency rates, complication rates, and intervention rates of PTFE and DHV were compared. RESULTS: The mean follow-up was 313 days for DHV (range 1-771) and 339 (3-909) days for PTFE. The total follow-up was 54.1 patient-years for DHV and 63.1 for PTFE. The 1-year primary patency rates were 30% and 40% for DHV and PTFE respectively. Secondary patency rate was 63% for both DHV and PTFE. Most frequent complication was thrombosis. A total of 75 thrombotic events (1.39 per patient-year) occurred in 35 (56%) DHV grafts and 78 (1.24 per py) in 36 (53%) PTFE grafts. A total of nine infections were seen in nine (14%) DHV grafts, whereas 21 infections in 20 (29%) PTFE grafts were seen (p = 0.08). All but one infected DHV graft could be salvaged with systemic antibiotics. In contrast, surgical intervention was necessary in nine PTFE grafts (p = 0.02). For aneurysms, eight DHV and two PTFE grafts needed revision (p = 0.03). CONCLUSION: Patency rates between DHV and PTFE were not different. More infections were seen in PTFE grafts, and significantly more PTFE grafts needed surgical revision or removal because of infection. Significantly more DHV grafts were surgically revised or removed because of aneurysms.

Aged↗
PubMed1998

Graft flow as a predictor of thrombosis in hemodialysis grafts.

BACKGROUND: The effort to reduce the incidence of graft thrombosis is mainly based on predicting venous stenosis by measuring venous drip chamber pressures. In this study we evaluated whether graft flow measurements, using an ultrasound dilution technique, would be of additional value to identify patients at risk for thrombosis. METHODS: In fifty consecutive patients with a bridge graft we measured graft flow and venous drip chamber pressure at a dialyzer blood flow of 200 ml/min. The results of these flow measurements were not used for selection of patients, nor for a diagnostic or therapeutic procedure. All thrombotic events and (radiological or surgical) interventions were registered. RESULTS: A total of 17 patient-years were analyzed. In 17 patients an intervention was done, and in 18 patients thrombosis occurred. The incidence rate of thrombosis was higher in patients with a flow < 600 ml/min (N = 13) compared to patients with a flow > 600 ml/min (N = 37; rate ratio 7. 2; 95% CI, range 2.84 to 18.24, P < 0.001). In 4 patients with a flow < 600 ml/min an intervention was done within the first two months after the flow measurement. In the remaining 9 patients, 6 grafts thrombosed within this period. Five interventions were done in patients with a flow > 600 ml/min. In the remaining 32 patients only two developed spontaneous thrombosis. Remarkably, venous drip chamber pressure measurements did not discriminate between patients with graft flow > or < 600 ml/min, and showed a wide range in patients who developed spontaneous thrombosis within two months. CONCLUSION: We suggest that graft flow measurements are helpful in selecting patients at risk for graft thrombosis.

Catheters, Indwelling↗
PubMed1998

Proportionate increase of fibrinogen and albumin synthesis in nephrotic patients: measurements with stable isotopes.

Hyperfibrinogenemia is a common feature of the nephrotic syndrome, and contributes to increased tendency for thrombosis and atherosclerosis. Its genesis is not certain, but the increase in liver fibrinogen mRNA in nephrotic rats indicates increased synthesis. Data in humans are scarce. We presently compared synthesis rates of fibrinogen and albumin in nephrotic adults (N = 7; plasma albumin 22.3 +/- 0.7 g/liter, proteinuria 12 g/day) and healthy control subjects (N = 8) using a primed/continuous infusion of the stable isotope L-[1-13C]valine for six hours. Absolute synthesis rate (ASR) of fibrinogen was 31 +/- 3 mg/kg/day in nephrotic subjects and 21 +/- 1 mg/kg/day in control subjects (P < 0.05), and positively correlated with plasma fibrinogen (P = 0.0317). The plasma fibrinogen pool was disproportionately increased in the nephrotic patients (271 +/- 30 mg/kg) compared to the controls (126 +/- 8 mg/kg), suggesting decreased fractional catabolic rate as well. The ASR of albumin was increased from 71 +/- 4 mg/kg/day in the controls to 160 +/- 19 mg/kg/day in the patients (P < 0.0001), and strongly correlated with the ASR of fibrinogen (P = 0.0046). Plasma alpha 2-macroglobulin was also elevated and correlated with the albumin synthesis rate, whereas plasma serum amyloid A and C-reactive protein were not elevated. These data suggest that in nephrotic patients the increased albumin synthesis is associated with an increase in synthesis of a specific and coordinated group of proteins, among which is fibrinogen.

Adult↗
PubMed1998

Effect of an increase in the plasma potassium concentration on renal magnesium handling in healthy volunteers.

BACKGROUND: Lower plasma magnesium concentrations are associated with clinical problems such as arrhythmias and hypertension. Plasma magnesium concentration is tightly controlled by the kidney. Modifying renal magnesium threshold may provide a means to increase the plasma magnesium concentration. Since evidence has been presented that potassium deficiency by itself may increase renal magnesium loss, the hypothesis that elevating plasma potassium would result in an increase in plasma magnesium concentration was tested in healthy volunteers. METHODS: Plasma potassium was raised in nine healthy volunteers by oral administration of 20 mg amiloride daily during 3 weeks. Magnesium metabolism was assessed before and after this period by plasma levels, urinary magnesium excretion and fractional magnesium excretion, and magnesium loading test (MLT). This MLT allows calculation of renal retention of a magnesium load. RESULTS: Basal plasma magnesium levels (0.84 +/- 0.07 vs 0.84 +/- 0.05 mmol/l) as well as urinary magnesium excretion (4.37 +/- 1.73 vs 3.67 +/- 1.37 mmol/day) and erythrocyte magnesium levels (1.72 +/- 0.16 vs 1.76 +/- 0.14 mmol Mg/l red blood cells) were similar before and on amiloride. Plasma potassium rose significantly on amiloride (3.64 +/- 0.24 vs 4.07 +/- 0.54 mmol/l, P < 0.05). No change was observed in magnesium retention with the MLT: 22.7 +/- 26.7 vs 29.2 +/- 20.6% (P = 0.5). CONCLUSIONS: Despite an increased plasma potassium concentration, no change was observed in plasma magnesium levels, urinary magnesium excretion or renal magnesium retention of an intravenously administered magnesium load. This indicates that increasing plasma potassium within the normal range does not modify the renal magnesium threshold.

Adult↗
PubMed1998

Daily home haemodialysis in The Netherlands: effects on metabolic control, haemodynamics, and quality of life.

BACKGROUND: More frequent dialysis has been claimed to improve clinical outcome and quality of life. METHODS: Clinical status was optimized in 13 haemodialysis patients during a run-in period of 2 months with three dialysis sessions a week. Thereafter, daily home haemodialysis (DHHD, 6 sessions per week) was initiated. The total weekly dialysis dose (Kt/V) was kept constant. RESULTS: Weekly Kt/V was 3.2+/-0.13 (M+/-SEM) before, and 3.2+/-0.15 after 6 months of DHHD (NS), time-averaged concentration of urea (TACu) was 21.2+/-1.6 mmol/l and 20.1+/-0.9 mmol/l (NS). Urea reduction was 0.56+/-0.05 before DHHD, and 0.41+/-0.06 during DHHD (P<0.0001). Serum K remained unchanged, but significantly less exchange resins were used (P<0.02). Also, the dose of phosphate-binding agents could be decreased. Values for Na, K, Cl, bicarbonate, Ca, PTH, albumin, and Hb remained unchanged. Iron deficiency developed in some patients. Twenty-four-hour blood pressure monitoring showed a decrease of systolic blood pressure (141.1+/-17.2 mmHg before, and 130.9+/-19.2 mmHg during DHHD, P<0.001). Diastolic blood pressure remained constant (82.8+/-7.2 and 76.9+/-10.1 mmHg, NS). Mean arterial pressure decreased from 102.2+/-9.5 to 94.9+/-1.4 mmHg (P<0.02). Blood pressure decreased mainly in previously hypertensive patients. Mean target weight increased 0.8 kg. The amount of antihypertensive drugs used decreased from 1.88+/-0.35 to 0.75+/-0.17 (P<0.005, n=7). Dialysis sessions were much more stable, also in patients with cardiac insufficiency. Quality of life questionnaires (Rand 36, Nottingham Health Profile, Uraemic Symptoms Profile) showed a significant improvement of physical condition and fewer uraemic symptoms. CONCLUSION: DHHD compared to conventional thrice-weekly haemodialysis with similar weekly Kt/V results in an improved haemodynamic control and quality of life, but has lesser impact on metabolic regulation.

Adult↗
PubMed1998

Effects of a nitric oxide synthesis inhibitor on renal sodium handling and diluting capacity in humans.

BACKGROUND: Inhibition of nitric oxide (NO) synthesis has antinatriuretic and antidiuretic effects. Limited information is available on the role of NO in tubular sodium transport in the human kidney. METHODS: We studied nine healthy, sodium-replete males with clearance techniques during maximal diuresis. NG-monomethyl-L-arginine (L-NMMA, 3 mg/kg priming dose plus 3 mg/kg/h) was infused for 3 h, to achieve steady-state inhibition of NO synthesis. Data were compared with a time control study. RESULTS: The effects of L-NMMA were quickly established and persisted through the entire infusion period. Mean arterial pressure increased slightly from 85+/-3 to 91+/-3 mmHg (P<0.05). Renal plasma flow decreased substantially, and glomerular filtration rate slightly. Large decreases in absolute sodium excretion, from 79+/-10 to 34+/-5 micromol/min (P<0.01), and fractional sodium excretion, from 0.5+/-0.0 to 0.3+/-0.0% (P<0.01), were associated with significant reductions in fractional lithium excretion (P<0.05) and maximum urine flow (P<0.01). Minimal urine sodium concentration decreased from 5.8+/-0.04 to 3.9+/-0.4 mmol/l (P<0.01) whereas minimal urine osmolality increased (P<0.05). Plasma renin activity, aldosterone and atrial natriuretic peptide levels did not change, whereas urinary excretions of guanosine 3'5'-cyclic monophosphate and of nitrite plus nitrate decreased slightly. CONCLUSIONS: Inhibition of endogenous NO synthesis in humans to an extent that raises blood pressure only mildly causes antinatriuresis, that can be attributed to increases in sodium reabsorption both at proximal and distal nephron sites. In addition, renal diluting capacity decreases. The effects in the diluting segment have not been reported before, and may be due to medullary vasoconstriction, similar to that described for angiotensin II.

Adult↗
PubMed1998

Tubuloglomerular feedback and prolonged ACE-inhibitor treatment in the hypertensive fawn-hooded rat.

BACKGROUND: The spontaneously hypertensive fawn-hooded (FHH) rat develops severe glomerulosclerosis with ageing. The afferent arteriolar resistance is low, resulting in a strongly elevated glomerular capillary pressure (P(GC)). METHODS: Afferent arteriolar resistance is under the control of the tubuloglomerular feedback (TGF) system, and we studied whether young FHH rats, i.e. at a stage when only mild glomerulosclerosis was present, have diminished TGF responsiveness. RESULTS: Maximum TGF-mediated decreases in stop-flow pressure in response to late proximal perfusion with artificial tubular fluid were 9.0 +/- 1.0 mmHg, a value not different or even slightly lower than observed in normal rats. P(GC) was 59.9 +/- 1.2 mmHg and the estimated P(GC) at half-maximal activation of the TGF system (operating P(GC)) was 54.5 +/- 0.8 mmHg at 11 weeks of age (n = 11), a value higher than observed in normal rats. The second question of the present study concerns the effect of chronic angiotensin-I-converting enzyme inhibitor (ACE-i) administration on P(GC). ACE-i, by reducing angiotensin II (Ang II) availability, diminishes TGF responsiveness, which would offset the beneficial effect on P(GC) under normal flow conditions to the macula densa. Maximum TGF responses were 8.9 +/- 1.0 and 17.5 +/- 1.5 mmHg in 11- and 26-week-old rats that had been treated with the ACE-i lisinopril in the drinking water started when the animals were 7 weeks of age. P(GC) was 44.3 +/- 1.2 (n = 9) and operating P(GC) was 40.1 +/- 1.6 mmHg (n = 9) at 11, values significantly lower than in untreated rats. Values remained lower in the 26-week-old treated animals and were 40.9 +/- 0.8 and 32.6 +/- 1.1 mmHg. CONCLUSIONS: (1) the TGF system in this model of spontaneous hypertension and glomerulosclerosis is intact, despite the fact that the FHH rat has a characteristically low afferent arteriolar resistance as compared to other hypertensive rats; (2) the rat displays a normal or even enhanced function of the TGF system following prolonged administration of the ACE-i lisinopril. The latter finding indicates that the reduction of P(GC) achieved by the ACE-i is not offset by a concomitant attenuation of TGF function.

Angiotensin II↗
PubMed1998

Presyncope during progressive hypovolaemia simulated by lower body negative pressure is not prevented by high-dose naloxone.

BACKGROUND: The haemodynamic response to progressive hypovolaemia, whether simulated by lower body negative pressure (LBNP) or head-up tilt, or induced by haemorrhage or haemodialysis, has a typical biphasic pattern: a first, sympathoexcitatory, phase of vasoconstriction, tachycardia, and stable blood pressure, and a second, sympathoinhibitory, phase of vasodilatation, bradycardia, and hypotension. The opioid system is involved in this response, since animal studies showed that opioid antagonism by naloxone can attenuate hypovolaemic hypotension. In humans, this finding could not be confirmed. We hypothesized that this could result from inadequate dosing. METHODS: Six healthy subjects underwent LBNP at -45 mmHg until presyncope before and after administration of naloxone 2 mg/kg. During the study, blood pressure, heart rate, vascular resistance, cardiac output, and plasma beta-endorphin were measured. RESULTS: LBNP caused an immediate increase in vasoconstriction and heart rate, resulting in stable blood pressure. After 12 +/- 3.5 min, vasodilatory hypotension followed, accompanied by a modest increase in plasma beta-endorphin. Naloxone did not alter the first or the second phase of the circulatory response, and tolerance to LBNP even tended to decrease (hypotension after 7.5 +/- 2.0 min, NS). Pre-LBNP plasma beta-endorphin as well as hypotensive levels were increased after naloxone. CONCLUSIONS: Our results suggest that naloxone, in a sufficient dose to interfere with the opioid system, does not influence the circulatory response to simulated hypovolaemia in humans is not influenced by naloxone. Given the mechanistic resemblance of LBNP hypotension to dialysis-induced hypotension, we propose that high-dose naloxone is not useful to treat the latter form of hypotension.

Adult↗
PubMed1998

Progressive vascular damage in hypertension is associated with increased levels of circulating P-selectin.

OBJECTIVE: To assess whether increased shedding of adhesion molecules in plasma provides an index for endothelial damage in hypertension. DESIGN AND METHODS: Three groups of hypertensive patients with increasing severity of vascular damage were studied: 20 essential hypertensives, 21 atherosclerotic, renovascular hypertensives and four malignant hypertensives. Twenty healthy subjects were included as a control group. Levels of P-selectin, E-selectin, intracellular adhesion molecule 1, vascular cell adhesion molecule and von Willebrand factor in venous blood were measured, using sandwich-type enzyme-linked immunosorbent assay. RESULTS: For essential hypertensives a trend for increased P-selectin and E-selectin values compared with those in controls was observed (159+/-44 versus 132+/-40 ng/ml, P = 0.062 and 40+/-13 versus 34+/-17 ng/ml, P = 0.055, respectively). P-selectin (210+/-84 ng/ml, P = 0.0021) and E-selectin (42+/-12 ng/ml, P = 0.012) levels in renovascular hypertensives were significantly higher than those in healthy controls. There were no significant increases in circulating levels of intracellular adhesion molecule 1, vascular cell adhesion molecule and von Willebrand factor either in essential hypertensives or in renovascular hypertensives. Marked increases in circulating levels of adhesion molecules and von Willebrand factor relative to those in controls were observed in malignant hypertensives (P-selectin 634+/-332 versus 132+/-40 ng/ml, P = 0.0004; vascular cell adhesion molecule 968+/-187 versus 493+/-139 ng/ml, P = 0.0004; and von Willebrand factor 259+/-75 versus 130+/-72 U/dl, P = 0.016). CONCLUSIONS: Progression of vascular damage in essential, renovascular and malignant hypertension is associated with a rise in circulating levels of P-selectins and, to a lesser extent, E-selectins, whereas levels of intracellular adhesion molecule 1, vascular cell adhesion molecule and von Willebrand factor are elevated only in diseases associated with acute severe vascular damage, including malignant hypertension. Our data suggest that selectins may be useful as indicators of vascular damage in hypertension.

Adult↗
PubMed1998

Losartan attenuates modest but not strong renal vasoconstriction induced by nitric oxide inhibition.

Previous studies showed variable success of angiotensin II (ANG II) antagonists to oppose systemic and renal vasoconstriction during long-term nitric oxide synthase (NOS) inhibition. We explored in short-term experiments whether the systemic and renal vasodilatory response to angiotensin II type 1 (AT1)-receptor blockade depends on the extent of NOS blockade. In the first series of experiments, anesthetized rats underwent clearance studies during continuous monitoring of mean arterial pressure (MAP), renal blood flow (RBF, flow probe), and renal vascular resistance (RVR). Compared with control animals, low-dose infusion of the NOS-inhibitor nitro-L-arginine (NLA) increased MAP and RVR, decreased glomerular filtration rate, RBF, and sodium excretion, and had no effect on plasma and kidney ANG II content. High-dose NLA induced stronger effects, did not affect plasma ANG II, and reduced kidney ANG II to approximately 60%. In the second series of experiments, we studied the effect of low- and high-dose NLA on autoregulation of RBF. NLA induced a dose-dependent increase in MAP and decrease in RBF but left autoregulation intact. The AT1-receptor antagonist losartan restored MAP and RBF during low-dose NLA but had no depressor or renal vasodilating effect during high-dose NLA. In summary, short-term NOS blockade causes a dose-dependent pressor and renal vasoconstrictor response, without affecting renal autoregulation, and AT1-receptor blockade restores systemic pressor and renal vasoconstrictive effects of mild NOS inhibition but fails to exert vasorelaxation during strong NOS blockade. Both levels of NOS inhibition did not importantly alter intrarenal ANG II levels. Apparently the functional role of endogenous ANG II as determinant of vascular tone is diminished during strong NOS inhibition.

Angiotensin II↗
PubMed1998

Estrogen induces glomerulosclerosis in analbuminemic rats.

Progression of chronic renal disease is usually more rapid in males, both in humans and in experimental animals. Estrogen-replacement studies indicate that this may be related to the beneficial effects of estrogen on the lipoprotein profile. However, in hyperlipidemic analbuminemic rats (NAR), females are more prone to develop renal injury than males, and ovariectomy tends to decrease triglyceride levels and prevent renal disease. Therefore, we studied the effects of estrogen administration on lipoproteins, and the induction of renal injury in uninephrectomized female and male NAR. Ovariectomized and orchidectomized uninephrectomized NAR were treated with estradiol implants for 24 weeks. In an additional group of ovariectomized rats, the implant was removed after 12 weeks. Both in ovariectomized and orchidectomized NAR, estradiol caused severe hypercholesterolemia (9 to 12 mmol/liter) and hypertriglyceridemia (6 to 8 mmol/liter) after six weeks. Subsequently, these rats developed severe proteinuria, reaching 209 +/- 25 and 95 +/- 43 mg/day, respectively, after 24 weeks. At this point there was severe glomerular sclerosis, with a respective score of 107 +/- 21 and 61 +/- 33. In terminal blood samples the most pronounced increase in lipid levels were observed in very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and low density lipoproteins (LDL). In contrast, ovariectomized NAR and orchidectomized NAR without exogenous estrogen had much lower lipid levels (cholesterol 5 to 7 mmol/liter and triglycerides 1 to 2 mmol/liter) after six weeks. These rats, or ovariectomized NAR where the estrogen treatment had been withdrawn, had practically no proteinuria (4 +/- 1, 19 +/- 11, and 13 +/- 4 mg/day, respectively) or renal damage (glomerulosclerosis score 1 +/- 0.4, 5 +/- 3 and 3 +/- 1, respectively) after 24 weeks. Thus, in hypertriglyceridemic analbuminemic rats, estrogen-treatment causes further increases in both triglycerides and cholesterol. Most probably these changes contribute to the development of renal injury by estrogen in this model. This effect of estrogen, which has also been observed in the Zucker rat, is unique for the hypertriglyceridemic state and deserves further study.

Albumins↗
PubMed1998

Angiotensin converting enzyme inhibitor-induced renal dysfunction in atherosclerotic renovascular disease.

Ischemic nephropathy due to bilateral renovascular disease (RVD) is increasingly recognized as cause of end-stage renal failure in the elderly, but a reliable non-invasive method of detection is nor available. Angiotensin converting enzyme inhibition (ACEi) may impair renal function in such patients, but a prospective study of its diagnostic validity has not been undertaken. We studied the effects of controlled exposure to ACEi on plasma creatinine in 108 patients at risk for severe bilateral atherosclerotic RVD, and compared the findings with subsequent angiography. ACEi was given for two weeks, or, to avoid acute renal failure, for four days if plasma creatinine had increased by 20% or more. If after two weeks of ACEi plasma creatinine had not increased by > or = 20%, while blood pressure was still elevated, plasma creatinine was remeasured after blood pressure control by addition of diuretics. The severity of RVD was scored by the stenosis grade of the best perfused kidney. Fifty-two patients had severe bilateral RVD, defined as > or = 50% stenosis to both kidneys (N = 23) or a solitary functioning kidney (N = 29). Of the others, 21 had less severe bilateral RVD, 20 unilateral RVD, and 15 no apparent RVD. Basal plasma creatinine was higher in severe bilateral RVD (median 170 mumol/liter, range 85 to 654 mumol/liter) than in the others (122 mumol/liter, 62 to 675 mumol/liter; P < 0.01), but not discriminative due to a large variability. The increase during ACEi was correlated with the degree of RVD (r = 0.53, P < 0.001). In 69 patients ACEi caused at least a 20% increase in plasma creatinine, in 26 cases by four days, in 31 after two weeks, and in 12 only after blood pressure control by diuretics. Among these were all 52 patients with severe bilateral RVD, 15 of the 41 patients with lesser forms of RVD, and two with normal renal arteries. Thus, in this selected population the criterion of > or = 20% rise in plasma creatinine upon ACEi was 100% sensitive to detect severe bilateral RVD, while its specificity was 70%. No case of acute renal failure was encountered, and plasma creatinine always recovered after stopping ACEi. In conclusion, controlled exposure to ACEi in these patients is safe, and ACEi-induced increase in plasma creatinine is a very sensitive detector of severe bilateral RVD in a high risk population.

Aged↗
PubMed1998

Proteinuria precedes cerebral edema in stroke-prone rats: a magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Stroke-prone spontaneously hypertensive rats (SHRSP) subjected to high sodium intake develop severe hypertension, cerebral edema, and proteinuria, culminating in organ damage and early death. MRI, which can be applied serially, provides the unique opportunity to study temporal and quantitative relations between these changes and whether diminution of sodium intake can attenuate established cerebral edema. METHODS: SHRSP were subjected to 1% NaCl in drinking water. Cerebral MRI, proteinuria and systolic blood pressure (SBP) were measured serially. After detection of cerebral edema (T2-weighted MRI), 6 rats were killed for histology, to confirm the diagnosis of cerebral edema. The others were followed up for 7 more days while salt loading was continued (n = 10, group 1) or after sodium intake was normalized (n = 7, group 2). RESULTS: SHRSP invariably developed cerebral edema in 30 days (range, 8 to 54 days). At this point neurological signs were absent in 16 of 23 rats. SBP rose until 1 week before detection of cerebral edema, and then stabilized at approximately 265 mm Hg. Proteinuria invariably preceded cerebral edema, with a concentration exceeding 40 mg/d predicting development of cerebral edema in 9 days (range, 3 to 15 days). There was linear correlation (R=.62, P<.0001) between proteinuria and cerebral edema (pixels with an intensity above a defined threshold). Rats in group 1 showed an increase in cerebral edema (from 5.8+/-1.1% to 12.5+/-2.8%; P<.05), and proteinuria remained high (from 305+/-44 to 338+/-29 mg/d); and 2 died spontaneously. Rats in group 2 showed no significant change in edema (from 4.9+/-0.5% to 6.9+/-1.3%) but a marked fall in proteinuria (from 294+/-24 to 119+/-10 mg/d; P<.05), both significantly different from group 1 (P<.05); all survived. SBP remained unaltered in both groups. CONCLUSIONS: Our data establish MRI as a sensitive method for detection of cerebral edema, often prior to neurological signs, in SHRSP. Proteinuria predicts cerebral edema, and these two variables, both obtained noninvasively, are quantitatively related. Moreover, in SHRSP normalizing sodium intake after salt loading attenuates development of cerebral edema and reduces proteinuria.

Animals↗
PubMed1998

Enalapril prevents imminent and reduces manifest cerebral edema in stroke-prone hypertensive rats.

BACKGROUND AND PURPOSE: Stroke-prone spontaneously hypertensive rats (SHRSP), subjected to high NaCl intake, show severe hypertension, organ damage, and early death. Preventive treatment with an angiotensin-converting enzyme (ACE) inhibitor is known to reduce mortality. Previously we found that proteinuria always precedes cerebral edema in SHRSP. Hence, in this study ACE inhibition was started later, ie, directly after manifestation of either proteinuria or cerebral edema. METHODS: SHRSP were subjected to 1% NaCl intake. Group 1 served as a control. In group 2 early-onset treatment with the ACE inhibitor enalapril was initiated after proteinuria was >40 mg/d. In group 3 late-onset ACE inhibition was started after the first observation of cerebral edema with T2-weighted MRI. Cerebral edema was expressed as the percentage of pixels with an intensity above a defined threshold. RESULTS: In controls median survival was 54 days (range, 32 to 80 days) after start of salt loading. The terminal level of cerebral edema was 19.0+/-3.0%. Under early-onset enalapril, median survival increased to 320 days (range, 134 to 368 days; P<0.01 versus group 1). Cerebral edema was prevented in all but 1 rat. Systolic blood pressure was slightly and transiently reduced at day 14. Proteinuria was markedly reduced (52+/-7 versus 190+/-46 mg/d in group 1 at day 7; P<0.05). Under late-onset enalapril, median survival was 264 days (range, 154 to 319 days; P<0.01 versus group 1). Cerebral edema decreased to baseline levels (9.6+/-2.9 at day 0 to 3.4+/-0.5% at day 3; (P<0.05). Ultimately cerebral edema reoccurred in 6 of the 8 rats. SBP decreased slightly at day 7 only. Proteinuria decreased from 283+/-27 at day 0 to 116+/-22 mg/d at day 7 (P<0.05). Complete remission of the original locus of cerebral edema was confirmed histologically. CONCLUSIONS: In SHRSP with proteinuria, treatment with an ACE inhibitor both prevented the development of cerebral edema and reduced manifest cerebral edema and proteinuria. Survival was markedly prolonged. These findings support the use of ACE inhibition for treatment in hypertensive encephalopathy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Hemodynamic response during lower body negative pressure: role of volume status.

Sudden dialysis-related hypotension is characterized by paradoxical vasodilation, suggestive of sympathoinhibition. A similar hypotensive reaction can be evoked by lower body negative pressure (LBNP), which thus allows the study of the numerous factors involved in dialysis hypotension separately. This article examines the influence of changes in volume status on the hemodynamic response to LBNP (45 mmHg up to the iliac crest, maximum 60 min) in 12 healthy subjects. LBNP caused a decrease in cardiac index and pulse pressure, and an increase in heart rate and total peripheral resistance, most of which developed within the first 3 min of LBNP. Six subjects developed sudden hypotension characterized by vasodilation after 9 +/- 4 min of LBNP. After saline expansion (25 ml/kg), which increased blood volume by approximately 8%, five subjects endured LBNP for the full 60 min. However, after 60 min of LBNP, the circulatory parameters suggested a similar critical situation as that observed before presyncope in their first experiment. The other six subjects endured the full 60 min of LBNP. After furosemide-induced volume reduction associated with 1.6 +/- 0.2 kg weight loss and approximately 7% blood volume reduction, five of them developed vasodilatory presyncope after 17 +/- 5 min of LBNP. Comparison of presyncopal and nonpresyncopal experiments within subjects, as well as between subjects, showed that the early (3 min) response to LBNP was different: Despite similar decreases in cardiac index, the values for systolic pressure, pulse pressure, peripheral resistance, and stroke volume were lower, and the heart rate was higher in the experiments ending in presyncope. It is concluded that the volume status is a determinant of the tolerance to LBNP, probably by affecting the vasoconstrictive response. By inference, this study suggests that the vasoconstrictive response to the hemodynamic stress of hemodialysis is also influenced by the volume status.

Adult↗
PubMed1998

Endothelin A receptor blockade alleviates hypertension and renal lesions associated with chronic nitric oxide synthase inhibition.

Unopposed actions of vasoconstrictors, such as angiotensin, play an important role in the effects of chronic nitric oxide synthase (NOS) inhibition. In this study, it is hypothesized that endothelin (ET), another important vasoconstrictor, may also play a role in the development of hypertension and renal lesions during chronic NOS inhibition. The ET(A) receptor was blocked with A-127722 during chronic NOS inhibition with Nomega-nitro-L-arginine (L-NNA), a potent NOS inhibitor without antimuscarinic action. Male Sprague Dawley rats were treated for 3 wk with L-NNA (40 mg/kg per d), L-NNA (40 mg/kg per d) + A-127722 (30 mg/kg per d), or remained untreated (control). In preliminary experiments, L-NNA (40 mg/kg per d) had been found to cause the maximum increase of systolic BP and a 35% decrease in renal NOS activity. Three weeks of L-NNA treatment resulted in a marked rise in systolic BP (240+/-4 versus control 151+/-7 mmHg; P < 0.01), proteinuria (209+/-46 versus control 27+/-3 mg/d; P < 0.01), and a fall in GFR (1.41+/-0.16 versus control 2.23+/-0.19 ml/min; P < 0.05). Renal morphology showed severe vascular injury, characterized by focal adhesion and infiltration of mononuclear cells into the intima and media of preglomerular arteries and arterioles. This was sometimes associated with necrosis of the media and partial or total obstruction of the lumen with thrombotic material. Ischemic glomeruli were also present. Tubulointerstitial damage was moderate and accompanied by an influx of monocytes and macrophages. A-127722 administered simultaneously with L-NNA completely prevented the increase in proteinuria (39+/-8 mg/d) and glomerular ischemia. Vascular injury, tubulointerstitial damage, and the increase in systolic BP (191+/-6 mmHg) were partially prevented. The protective effects of ET(A) receptor blockade suggest that ET has hemodynamic as well as nonhemodynamic effects in the cascade of events following chronic NOS inhibition.

Animals↗