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Biomedical subjects

L Raij

Publications and source records attributed to L Raij.

At least 91 records · Page 5Linked to original sources
PubMed1988

High potassium diet augments endothelium-dependent relaxations in the Dahl rat.

Endothelium-dependent relaxations are reduced in hypertensive rats. High dietary potassium supplementation reduces the incidence of strokes in Dahl rats independently of blood pressure, thereby suggesting a direct protective effect of the diet. Endothelium-dependent relaxations and aortic vascular architecture were studied in Dahl salt-sensitive rats fed 8% NaCl, 0.1% NaCl, or 8% NaCl plus 3.6% potassium citrate for 8 weeks. Rats fed 8% NaCl or 8% NaCl plus 3.6% potassium citrate became hypertensive, while those fed 0.1% NaCl did not. Aortic rings with and without endothelium were suspended in organ chambers filled with physiological salt solution (37 degrees C) and aerated with 95% O2, 5% CO2. In rings contracted with norepinephrine, acetylcholine and adenosine 5'-diphosphate caused endothelium-dependent relaxations that were significantly reduced in rats fed 8% NaCl as compared with those fed 0.1% NaCl. Potassium supplementation (8% NaCl/3.6% potassium citrate) significantly enhanced relaxations to acetylcholine in salt-sensitive rats, while those to adenosine 5'-diphosphate and thrombin were either minimally affected or unchanged. Relaxations to sodium nitroprusside were similar in rats with or without potassium supplementation. Hypertension significantly increased aortic medial and intimal thickness. Dietary potassium had no significant effect on the vascular architecture. These results suggest that high potassium diet enhances endothelium-dependent relaxations in Dahl rats at least in part independently of changes in blood pressure. Thus, potassium may be important for its protective effect against stroke and renal damage in this animal model of hypertension.

Acetylcholine↗
PubMed1988

Adverse effect of amphotericin B administration on renal hemodynamics in the rat. Neurohumoral mechanisms and influence of calcium channel blockade.

The effect of administration of amphotericin B (AMPHO) on renal hemodynamics was studied in the rat. Acute infusion (1.2 mg/kg) of AMPHO resulted in a significant fall in glomerular filtration rate (GFR) (0.82 vs. 1.33 ml/min, P less than .01) and renal plasma flow (3.38 vs. 6.24 ml/min; P less than .01) and a rise in renal vascular resistance (23.55 vs. 11.25 mm Hg.min/ml; P less than .05) compared with base-line values. Administration of AMPHO (5 mg/kg/day i.p.) for 21 days resulted in similar changes in GFR, renal plasma flow and renal vascular resistance. Pretreatment of rats with the angiotensin II receptor blocker, sar-gly angiotensin II, did not prevent the renal vasoconstriction or fall in GFR with AMPHO. Unilateral renal denervation did not prevent the decreased GFR or effective renal plasma flow after AMPHO when compared with the contralateral, innervated kidney. Pretreatment of rats with verapamil completely inhibited renal vasoconstriction during and after AMPHO. Verapamil markedly attenuated the fall in GFR observed during AMPHO (AMPHO + verapamil vs. AMPHO + vehicle; 0.73 vs. 0.26 ml/min; P less than .05); however, the GFR observed in the postinfusion period was significantly decreased (base line vs. final; 1.17 vs. 0.84 ml/min; P less than .01). The authors conclude that 1) the adverse renal hemodynamic effects of AMPHO are not directly mediated by the renin-angiotensin or renal sympathetic nervous systems and 2) pretreatment with verapamil completely prevents AMPHO-induced renal vasoconstriction.

Amphotericin B↗
PubMed1987

Differential effect of hemodialysis membranes on human lymphocyte natural killer function.

Lymphocytes exposed to cuprammonium cellulose membranes have been shown to exhibit depressed natural killer (NK) function. In the present study we investigated the extent to which three dialyzer membranes of different compositions suppressed human lymphocyte NK activity. Peripheral blood lymphocytes or T cells from normal donors were exposed in vitro to cuprammonium cellulose, cellulose acetate, or polycarbonate dialyzer membranes. After exposure to the membranes, NK activity of the cells was studied by using the NK-sensitive cell line K562 as targets. All three membranes adversely affected human lymphocyte NK function, with cuprammonium cellulose producing the most (70-80%) and polycarbonate producing the least (10-15%) suppression. Our results suggest that the composition of dialyzer membranes affects the extent to which the membranes impair human lymphocyte function. The use of more biocompatible membranes might lessen the potential clinical impact of abnormal NK function in hemodialysis patients.

Cellulose↗
PubMed1987

Multiple effects of calcium entry blockers on renal function in hypertension.

Characterization of the renal effects of calcium entry blockers has not been easy because the inhibition of Ca2+ cellular influx alters several regulatory functions. The ability of calcium blockers to dilate renal vasculature and to increase glomerular filtration rate is largely determined by the preexisting vascular tone. However, the increments in sodium excretion could occur without alterations in renal hemodynamics. Calcium blockers could increase sodium excretion by inducing a redistribution of renal blood flow toward juxtamedullary nephrons, by inhibiting tubuloglomerular feedback responses, or by a direct action on the tubular transport of sodium. These effects are poorly understood at present. In vitro studies show that the blockade of calcium entry enhances renin secretion and decreases prostaglandin synthesis. This dissociation has not been found during long-term administration, which has been proved to be effective for the treatment of essential hypertension with normal maintenance of renal function. In this respect, there are reports indicating that calcium blockers are particularly effective in a subgroup of patients with essential hypertension who exhibit subtle but detectable alterations in calcium metabolism. Further studies are needed to determine whether this significant response to calcium blockers is due to correction of an early defect of calcium cellular kinetics that initiated the increase in blood pressure.

Calcium Channel Blockers↗
PubMed1987

Endothelium-dependent vascular responses in normotensive and hypertensive Dahl rats.

Experiments were designed to study endothelium-dependent responses in salt-sensitive (DS) and salt-resistant Dahl rats (DR). The rats were fed a low sodium (0.1% NaCl) or high sodium (8% NaCl) diet for 8 weeks. Blood pressure in DS fed a high sodium diet was higher than that in the remaining animals. Aortic rings with and without endothelium were suspended for isometric tension recording. Acetylcholine, adenosine 5'-diphosphate, and thrombin induced endothelium-dependent relaxations that were significantly depressed in the aorta of DS fed a high sodium diet. The relaxations in response to sodium nitroprusside were only slightly, but significantly, depressed in DS fed a high sodium diet. Removal of the endothelium greatly enhanced the response to serotonin and norepinephrine. In rings with, but not without, endothelium taken from rats fed a high sodium diet, the tension developed in response to serotonin and norepinephrine was significantly greater than that in animals fed a low sodium diet. These experiments indicate that endothelium-dependent relaxations to acetylcholine, adenosine 5'-diphosphate, and thrombin are depressed in hypertensive Dahl rats; this effect probably reflects a decreased release of endothelium-derived relaxing factor(s), although structural changes might contribute; and the responsiveness to vasoconstrictor agents is increased in DS and DR fed a high sodium diet. These findings may indicate differential effects of blood pressure and dietary salt on endothelial function.

Acetylcholine↗
PubMed1987

Antihypertensive treatment normalizes decreased endothelium-dependent relaxations in rats with salt-induced hypertension.

Endothelium-dependent responses are impaired in various models of hypertension. The effects of antihypertensive treatment on endothelium-dependent relaxations were studied in Dahl salt-sensitive (DS) and Dahl salt-resistant rats (DR) on a high or low sodium diet. The rats were given either a diet containing 8% NaCl or 0.1% NaCl for 8 weeks or a diet containing 8% NaCl and a combination of reserpine, hydrochlorothiazide, and hydralazine for 8 or 2 weeks. DS on the 8% NaCl diet developed hypertension, while the other rats did not. Antihypertensive therapy for 8 or 2 weeks prevented or reversed hypertension in DS and lowered blood pressure in DR on the 8% NaCl diet. Aortic rings with and without endothelium were suspended in organ chambers for isometric tension recording. In all groups, acetylcholine, adenosine 5'-diphosphate, and thrombin caused endothelium-dependent relaxations. The relaxations in response to all agonists were significantly decreased in DS on 8% NaCl compared to relaxations in the other rats. Antihypertensive treatment for 8 or 2 weeks prevented or reversed the decreased endothelium-dependent relaxations in response to all agonists tested, but not those to the endothelium-independent agonist, sodium nitroprusside. These results suggest that antihypertensive treatment normalizes endothelium-dependent relaxations. This effect of antihypertensive treatment might be important for the prevention of cardiovascular complications in patients with hypertension.

Animals↗
PubMed1986

Opiates and the anorexia of uremia.

Uremia results in a decrease in food intake. In the present study we investigated whether opiates known to stimulate feeding would alter food intake in rats made uremic by 1 and 5/6 nephrectomy. Morphine increased food intake in sham nephrectomized rats, but failed to alter food intake in uremic animals and depressed the ingestion of rat chow in a group of weight restricted rats. Butorphanol tartrate increased feeding in sham and uremic animals but did not alter intake in the weight restricted group. Higher doses of butorphanol were needed to stimulate feeding in the uremic rats compared to the sham group, suggesting a relative resistance to opioid-induced feeding in the uremic rats. The opiate antagonist, naloxone, suppressed food intake in the uremic and sham groups more effectively than in the weight restricted rats. These data suggest that the opioid feeding system functions in a reduced fashion in uremic rats, but probably is not the sole factor involved in producing the anorexia associated with uremia.

Animals↗
PubMed1985

Glomerular mesangium: its function and relationship to angiotensin II.

The glomerular mesangium is composed of mesangial cells and an intercellular material, the mesangial matrix. Partly because of its unique anatomic location, the mesangium appears to be susceptible to immune- and non-immune-mediated injury. Mesangial cells have characteristics similar to smooth muscle cells, and their surface is covered with receptors that bind a variety of vasoactive substances. The glomerular mesangium seems to play an important role in the physiologic regulation of the glomerular microcirculation. There is evidence that a plasmic flow carrying macromolecules circulates through the mesangium. Changes in glomerular hemodynamic determinants and in the release and/or production of vasoactive substances, particularly angiotensin II, can greatly influence the mesangial movement of macromolecules. Quantitative and/or qualitative alterations in the mesangial movement of macromolecules may lead to mesangial injury.

Angiotensin II↗
PubMed1985

Therapeutic implications of hypertension-induced glomerular injury. Comparison of enalapril and a combination of hydralazine, reserpine, and hydrochlorothiazide in an experimental model.

Systemic hypertension does not always reflect concomitant glomerular hypertension. At similar levels of systemic hypertension, glomerular injury occurs only in kidneys that lack protective preglomerular vasoconstriction, which results in glomerular hypertension. indeed, glomerular hypertension and glomerular injury do not develop in rats with spontaneous hypertension that have effective preglomerular vasoconstriction. In the experiments reported herein, the normal adaptive response (afferent arteriolar dilation) to a reduction of one and five-sixths of the renal mass in rats with spontaneous hypertension was examined to ascertain whether that response would expose the remaining nephrons to the injurious effects of high perfusion pressure. In addition, the efficacies of two different antihypertensive regimens were compared. Rats with spontaneous hypertension received either no therapy, or a combination of hydralazine, reserpine, and hydrochlorothiazide, or the angiotensin converting enzyme inhibitor enalapril. Three weeks after ablation of one and five-sixths of the renal mass, blood pressure, glomerular filtration rate, urinary protein excretion, and histologic injury scores for mesangial expansion and glomerulosclerosis were determined. Untreated rats with hypertension had severe glomerulosclerosis and mesangial expansion. Both antihypertensive regimens normalized systemic blood pressure and reduced glomerulosclerosis. However, enalapril was more effective than the combination of hydralazine, reserpine, and hydrochlorothiazide in reducing the exaggerated glomerular filtration rate (0.52 +/- 0.40 versus 0.82 +/- 0.10 ml per minute; p less than 0.05), the injury score for mesangial expansion (79 versus 103; p less than 0.05), and the degree of proteinuria (32 +/- 4 versus 42 +/- 3 mg per 24 hours; p less than 0.05). Persistence of hyperfiltration accompanied by increased mesangial expansion, may lead to progression of glomerular damage despite "adequate" control of systemic hypertension, as observed in rats treated with a combination of hydralazine, reserpine, and hydrochlorothiazide.

Animals↗
PubMed1985

Adriamycin-induced chronic proteinuria: a structural and functional study.

Focal, segmental glomerulosclerosis is frequently associated with chronic proteinuria and progressively declining renal function in humans as well as in experimental models of glomerular disease. Although little is known regarding the pathogenesis of this lesion, persistent, massive proteinuria has been associated with a poor prognosis. The administration of adriamycin to rats results in proteinuria of glomerular origin. We used this model to study the glomerular functional and structural alterations associated with proteinuria of 4 to 5 weeks duration. Studies of single nephron function revealed a 34% reduction in nephron plasma flow and a 50% decline in the glomerular ultrafiltration coefficient in rats given adriamycin. Single nephron glomerular filtration rate, however, was only modestly reduced (27%), because of an 8.0 mm Hg elevation of mean transcapillary hydraulic pressure difference (P less than 0.05). Morphologically, glomeruli of adriamycin-treated rats demonstrated significantly increased mesangial matrix and cellularity. In addition, glomerular capillaries frequently appeared enlarged, and epithelial cell bleb formation was evident. Focal glomerulosclerosis, however, was only rarely seen. The functional and morphologic characteristics of chronic adriamycin nephrosis are different from those associated with chronic proteinuria induced by repetitive administration of aminonucleoside of puromycin. Comparison of the two models suggests that the development of focal glomerulosclerosis can be dissociated from proteinuria and elevations of intraglomerular hydraulic pressures.

Animals↗
PubMed1985

Relationship among altered glomerular barrier permselectivity, angiotensin II, and mesangial uptake of macromolecules.

Clinical and experimental studies suggest that accumulation of phlogogenic macromolecules in the glomerular mesangium may lead to mesangial expansion and eventual glomerulosclerosis. In focal glomerulosclerosis and nephrotic syndrome entrapment of macromolecules is observed in areas of glomerulosclerosis. To determine whether mesangial uptake of radiolabeled, heat-aggregated IgG (AG125I), a biologically active macromolecular protein, is influenced by increased glomerular filtration barrier permeability, we evaluated the glomerular uptake of AG125I in three models of proteinuria: aminonucleoside of puromycin nephropathy (PAN), adriamycin nephropathy, and Heyman's nephropathy. Rats were studied approximately 1 week after onset of proteinuria. AG125I was measured in preparations of isolated glomeruli and compared to simultaneous blood, liver, and spleen levels. Only rats with PAN had a marked increase in glomerular AG125I compared to control rats, 7.8 versus 2.6 micrograms/mg of glomeruli, respectively. We then evaluated whether a continuous infusion of a competitive inhibitor of angiotensin II, saralasin (300 micrograms/kg of body weight/minute), influenced mesangial uptake of AG125I in PAN rats. Strikingly, glomerular AG125I in rats with PAN was reduced to levels comparable to that observed in control rats infused with only saralasin, 2.8 versus 3.0 micrograms/mg of glomeruli, respectively. This effect on glomerular AG125I content was independent of any significant effect of saralasin on blood, hepatic, or splenic levels of AG125I. Moreover, these changes in glomerular AG125I in saralasin-infused rats with PAN did not appear to directly correlate with changes in whole kidney function. These studies also demonstrated that proteinuria per se did not influence mesangial uptake of macromolecules. Thus, these data indicated that angiotensin II had an important effect on intraglomerular factors that modulate mesangial localization of phlogogenic macromolecules.

Angiotensin II↗
PubMed1985

Age is a determinant of the glomerular morphologic and functional responses to chronic nephron loss.

Loss of renal mass results in a compensatory increase in growth and function of remaining nephrons. Renal ablation also accelerates the expansion of mesangial matrix and the development of focal glomerulosclerosis (FGS) associated with aging. To determine whether age at the time of nephron loss influences the compensatory changes in function and the severity of subsequent glomerular lesions, immature rats (group I) and adult rats (group II) underwent right unilateral nephrectomy (Nx). Four weeks after Nx, compensatory renal growth and single nephron function showed a similar pattern in both groups. Five months after Nx, however, group I displayed significantly greater compensatory growth than group II, although both groups exhibited similar single nephron function. Moreover, group II demonstrated a significant increase in mean transcapillary hydraulic pressure difference (delta P) of approximately 5 mm Hg. Although both groups experienced accelerated expansion of mesangial matrix, significant FGS was detectable only in group I. Thus glomerular injury after Nx may result from factors other than alterations in glomerular hemodynamics.

Aging↗
PubMed1984

Mesangial immune injury, hypertension, and progressive glomerular damage in Dahl rats.

Hypertension frequently accompanies chronic glomerulonephritis. Mesangial injury and glomerulosclerosis are common in glomerulonephritis and are often harbingers of progressive glomerular destruction. Thus, in a model of mesangial immune injury we studied the relationship between hypertension, mesangial injury, and glomerulosclerosis. We induced mesangial ferritin-antiferritin immune complex disease (FIC) in Dahl salt-sensitive (S) and salt-resistant (R) rats. S and R rats with FIC were fed chow containing 0.3% NaCl until 14 weeks of age and then switched to 8.0% NaCl chow until 28 weeks of age. Groups of control S and R rats (no FIC) were either fed 0.3% NaCl for 28 weeks or switched to 8.0% NaCl chow at 14 weeks of age. Blood pressure, serum creatinine, urinary protein, and glomerular injury (assessed by semiquantitative morphometric analysis) were determined at 14 and 28 weeks of age. R rats with or without FIC did not develop hypertension; mesangial injury was minimal. At 14 weeks of age, only S FIC rats developed hypertension, proteinuria, significant mesangial expansion and early glomerulosclerosis. At 28 weeks of age, proteinuria, mesangial expansion, and glomerulosclerosis were significantly more severe in hypertensive S rats with FIC than in those without FIC. These studies show that despite a normal salt intake, mesangial injury hastened the onset of hypertension, but only in rats genetically predisposed to hypertension (S FIC at 14 weeks). High dietary salt further aggravated hypertension, which, in turn, magnified both mesangial injury and glomerulosclerosis. Clinically, the different rates of progression of human glomerulonephritis associated with hypertension may be in part dependent on similar mechanisms.

Animals↗
PubMed1981

Mononuclear phagocytic system stimulation. Protective role from glomerular immune complex deposition.

Experimentally, glomerular deposition of circulating IC is increased when the MPS is saturated. Clinically, an association between glomerulonephritis and dysfunction of MPS-Fc receptor-mediated clearance of IC has recently been described in patients with certain forms of autoimmune diseases. Thus we hypothesized that stimulation of the MPS may be beneficial, by decreasing circulating IC and hence, reduce glomerular deposition of IC. To test this experimentally, we studied glomerular uptake and disappearance of AHIgG . 125I (macromolecular proteins biologically akin to IC) in normal control rats and in rats with ZY-stimulated MPS. ZY-treated and control rats were given 30 mg/100 gm body weight AHIgG . 125I and sacrificed at 30 min and 1, 2, 4, 8, 16, and 24 hr after AHIgG . 125I injection. Glomerular AHIgG . 125I was measured in preparations of isolated glomeruli and compared to simultaneous liver, spleen, lung, and blood greater than 7S AHIgG . 125I. The blood t 1/2 of greater 7S AHIgG . 125I in ZY rats was 40% shorter than that in control rats. Blood greater than 7S AHIgG . 125I in ZY rats was 63% lower than in control rats at 4 hr and 73% lower at 8 hr after injection. At all time intervals, glomerular AHIgG . 125I was reduced in ZY rats proportionately to the decreased blood levels. By immunofluorescence microscopy, the intensity of staining for human IgG correlated with the quantitative determination of AHIgG . 125I in preparations of isolated glomeruli in control and ZY rats. The reduction in blood and glomerular AHIgG . 125I in ZY rats was a result of a marked increased in hepatic and splenic uptake of AHIgG . 125I. Serum complement depletion of ZY rats with CVF prior to AHIgG . 125I injection did not significantly alter the kinetics of AHIgG. 125I. This suggests that the increased MPS uptake of AHIgG . 125I in ZY rats was predominantly Fc-receptor-mediated. Thus ZY stimulation of the MPS increased the clearance of AHIgG . 125I and protected glomeruli from AHIgG . 125I deposition. Clinically, agents that would specifically stimulate the MPS may be useful in reducing IC-mediated glomerular injury.

Animals↗