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Biomedical subjects

I Ichikawa

Publications and source records attributed to I Ichikawa.

At least 127 records · Page 7Linked to original sources
PubMed1988

"Intact nephrons" as the primary origin of proteinuria in chronic renal disease. Study in the rat model of subtotal nephrectomy.

Single nephron filtration rate of albumin (SNGFRAlb) was measured in remnant nephrons of Munich-Wistar rats 4-6 wk after subtotal nephrectomy (NPX). Serial thin-section histological analysis was then conducted on the same glomeruli by light microscopy. SNGFRAlb ranged from 1 to 15 times normal. However, a direct relationship between abnormalities of structure and function was not seen, e.g. the glomeruli with the fewest structural abnormalities and marked hyperfiltration often had the highest SNGFRAlb. Moreover, the majority of glomeruli had minimal structural abnormalities. Normalization of the markedly elevated glomerular capillary pressure (PGC) in these glomeruli was accomplished by acute intravenous infusion of verapamil, which decreased SNGFRAlb by 9-83% without affecting the single nephron filtration rate of water (SNGFRH2O). 1-2 wk after subtotal NPX, all glomeruli were hyperfiltering and had elevated PGC. The fractional clearance of larger (greater than 36 A) dextrans was selectively increased in these glomeruli that lacked discernible damage by light microscopy. Verapamil normalized PGC, reduced proteinuria to 48 +/- 4% of baseline, and improved glomerular size selectivity without altering SNGFRH2O. Proteinuria after subtotal NPX thus originates largely from glomeruli with minimal structural abnormalities. The defect in size selectivity is largely attributed to the prevailing high PGC, producing large, nonselective channels on the glomerular capillary wall. The observations raise the possibility that in chronic renal diseases, the reduction in proteinuria often seen after therapeutic measures, including antihypertensive medication, may reflect their functional effect on the relatively intact glomeruli rather than their structure-sparing effect on severely damaged glomeruli, which contribute little to the proteinuria.

Animals↗
PubMed1987

Pulmonary response to exposure to ozone of emphysematous rats.

Rats were treated with a single intratracheal instillation of 6.5 units elastase or normal saline. Seven weeks after treatment, the animals were exposed for 24 hr to filtered air or 1 ppm O3, and their lung functions were measured. The exposure to O3 resulted in functional changes depending mainly on peripheral airway obstruction, and the direction and degree of those functional changes were in general similar between the saline- and elastase-treated animals. Another group of saline- or elastase-treated rats were exposed to 3 ppm O3 for 3 hr and the edematous response of their lungs was again similar. These results indicate that elastase-treated lungs responded to the exposure to O3 in a fashion similar to normal lungs in rats, but lung damage caused by the exposure to O3 superimposed over preexisting emphysematous damage, resulted in an additional lessening of the margin of pulmonary reserve capacity.

Animals↗
PubMed1987

Effects of leukotriene D4 on glomerular dynamics in the rat.

Glomerular micropuncture studies were performed in euvolemic, anesthetized, adult, male Munich-Wistar rats to evaluate the glomerular microcirculatory actions of leukotriene D4 (LTD4). In preliminary experiments, intrarenal arterial administration of LTD4 (1 microgram X kg-1 X min-1) was found to cause a rise in mean systemic arterial pressure, a loss of plasma volume, and a fall in renal blood flow, effects identical to those previously reported for LTC4. To assess the local glomerular actions of LTD4 independently of these systemic effects, glomerular microcirculatory dynamics were assessed during LTD4 infusion while constancy of renal perfusion pressure and plasma volume were maintained by partial aortic constriction and isoncotic plasma infusion, respectively. To ascertain the LTD4 actions that are independent of angiotensin II, saralasin (5 micrograms X kg-1 X min-1 iv) was also given throughout the study. LTD4 caused a significant increase in efferent arteriolar resistance in association with a fall in glomerular plasma flow rate (QA) and a rise in glomerular capillary hydraulic pressure. Despite the latter, single-nephron filtration rate fell due to combined reductions in QA and the glomerular ultrafiltration coefficient. These local glomerular constrictor actions of LTD4 support the possibility that this eicosanoid might play an important intermediary role in the functional impairment accompanying some forms of inflammatory injury.

Animals↗
PubMed1987

Role of abnormally high transmural pressure in the permselectivity defect of glomerular capillary wall: a study in early passive Heymann nephritis.

To explore the mechanism of glomerular permselectivity defect in passive Heymann nephritis, an experimental model of human membranous glomerulopathy, Munich-Wistar rats were subjected to both micropuncture assessment of glomerular hemodynamics and whole kidney clearance measurements of graded size dextrans 10 days after injection of sheep anti-rat tubular antigen (anti-Fx1A). Compared with normal control rats, anti-Fx1A-treated animals were characterized by marked proteinuria (65 +/- 8 micrograms/min versus 6 +/- 1, p less than 0.001), markedly and significantly higher glomerular transcapillary hydraulic pressure difference (40 +/- 1 mm Hg versus 33 +/- 1, p less than 0.001), depressed ultrafiltration coefficient and impaired glomerular size-selective function as determined by fractional clearance of dextrans. Calculation of membrane parameters based on a recently defined heteroporous membrane model revealed abnormally high availability of non-size selective, large pore pathways in the glomerular capillary wall of the rats with passive Heymann nephritis. To ascertain the role of the altered hemodynamic pattern in the observed defect in the size-selective function of the glomerular capillary wall, glomerular transcapillary hydraulic pressure difference was manipulated experimentally in these proteinuric rats by intra-aortic infusion of acetylcholine or angiotensin II. These agents respectively suppressed and augmented glomerular transcapillary hydraulic pressure difference and brought about a decline of and a further rise in fractional clearance of larger dextrans along with parallel changes in both urine protein excretion rate and availability of nonselective channels. These results indicate that the permselectivity defect in passive Heymann nephritis is attributable, at least in part, to impaired size selectivity of the glomerular capillary wall caused by a prevailing abnormally high transcapillary hydraulic pressure difference.

Animals↗
PubMed1986

Role for angiotensin II in an overt functional proteinuria.

A partial renal vein constriction (RVC) was induced acutely in Munich-Wistar rats. RVC caused a marked reduction in glomerular plasma flow rate, and rises in glomerular transcapillary hydraulic pressure difference and efferent arteriolar resistance. These changes were associated with a marked increase in urinary protein excretion, on average from a baseline level of 8 to approximately 120 mg/24 hrs per kidney. Infusion of saralasin, an angiotensin II (AII) antagonist, largely normalized these indices, including urinary protein excretion (to approximately 35 mg/24 hrs per kidney), despite continued RVC. In separate rats, fractional clearances of neutral [125I]dextrans (molecular radii = 18-60 A) (CDEX/CIN) were measured. RVC caused a significant increase in CDEX/CIN for large dextrans (greater than or equal to 44A), but not small dextrans (less than or equal to 42A). Saralasin infusion led to a partial return toward baseline values of CDEX/CIN for the large dextrans. On the basis of the heteroporous membrane theory for glomerular filtration, the glomerular sieving defect during RVC was attributed to an increase in the relative fluid flux through a group of large non-selective pores. A marked alteration in glomerular microcirculatory pattern induced by enhanced action of endogenous AII in turn seemed to account largely, although not entirely, for the impairment of glomerular size-selectivity during RVC.

Angiotensin II↗
PubMed1986

Role of peritubular capillary forces in the renal action of carbonic anhydrase inhibitor.

Micropuncture study was performed in Munich-Wistar rats to assess peritubular capillary Starling forces in renal superficial cortex during suppression of proximal fluid reabsorption by carbonic anhydrase inhibitor. Administration of benzolamide (2 mg/kg/hr, i.v., Group 1, N = 7 rats) caused not only reduction in absolute rate of proximal fluid reabsorption (APR, from 26.7 +/- 4.0 nl/min to 17.7 +/- 3.6, P less than 0.001), but also an increase in peritubular transcapillary hydraulic-pressure difference (from 10.0 +/- 0.5 mm Hg to 15.2 +/- 0.5, P less than 0.001). In a separate group of seven rats (Group 2), these parameters did not change significantly without benzolamide treatment. In Group 1 rats, an attempt was made to nullify the benzolamide-induced reduction in the peritubular capillary net reabsorptive forces by infusing hyperoncotic high-hematocrit blood. Following this treatment, while benzolamide administration was continued, values for APR returned to levels (25.6 +/- 4.8 nl/min) nearly identical to those measured prior to benzolamide administration, in association with a rise in peritubular transcapillary oncotic pressure difference. A separate group of six rats treated in a fashion identical to that of Group 1 showed continued suppression of carbonic anhydrase activity following blood infusion as indicated by low levels of whole kidney bicarbonate reabsorption rate. Peritubular capillary reabsorption coefficient was calculated based on the measured values for Starling forces in Group 1 and were unaffected throughout the study. Continued benzolamide administration alone without the treatment of hyperoncotic blood did not change APR significantly (Group 3, N = 7 rats).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Interglomerular heterogeneity of filtration fraction among superficial nephrons: fact or artifact.

The variance (S2inter-G) in protein concentration (CE) of plasma samples collected by micropuncture from randomly chosen surface efferent arterioles was compared to the variance (S2intra-G) of samples collected and re-collected from the same efferent arterioles in 23 Munich-Wistar rats. During efferent arteriolar blood collection, an oil droplet was maintained with gentle suction downstream to the collection pipette to avoid disturbance of natural glomerular blood outflow. S2inter-G averaged 0.067 +/- 0.014 (SE), a value comparable to mean S2intra-G (0.075 +/- 0.016, P greater than 0.50), indicating that the degree of interglomerular heterogeneity in the value of filtration fraction is too small to detect with this micropuncture technique. When ten additional samples were collected using uncontrolled suction pressure, S2inter-G averaged 1.15 +/- 1.30, a value markedly greater than that obtained with controlled pressure. In six nephrons which possessed both glomeruli and efferent arterioles on the surface of the kidney, glomerular capillary pressure (PGC) was monitored during efferent arteriolar blood collection. Applying widely varied suction pressure, PGC changed as much as 42 mmHg, suggesting that improper suction pressure can alter glomerular pressures and flows, hence filtration fraction and CE. Thus, unlike renal proximal tubules, some of the rat renal efferent arterioles do not function as Starling resistors, which may, in turn, account for the wide variability in CE values reported recently by some investigators.

Animals↗
PubMed1986

Renal and systemic hemodynamic effects of synthetic atrial natriuretic peptide in the anesthetized rat.

To characterize the hemodynamic events responsible for alterations in renal function during administration of atrial natriuretic peptide, we studied the systemic, renal, and glomerular circulatory effects of intravenous rANP[126-149], administered as a 4 micrograms/kg prime and 0.5 microgram/kg per minute continuous infusion in anesthetized, euvolemic rats. With this protocol, a small decline in mean systemic arterial blood pressure occurred in the context of markedly enhanced urinary sodium excretion, hemoconcentration, and reduced left ventricular end-diastolic pressure and +dP/dt. However, despite a significant decrement in renal vascular resistance, total peripheral resistance remained constant, thereby denoting a preferential renal vasodilatory effect of this peptide in vivo. Whole kidney and single nephron GFR increased by approximately 20%, while effective renal and glomerular plasma flow rates remained stable, resulting in a substantial rise in filtration fraction. Of all the parameters potentially capable of augmenting single nephron GFR, only glomerular capillary hydraulic pressure increased significantly and therefore accounted entirely for the hyperfiltration observed during ANP infusion. This rise in glomerular capillary pressure, in turn, resulted from afferent arteriolar vasodilatation and concurrent efferent arteriolar vasoconstriction, findings that proved independent of both endogenous angiotensin II activity and ANP-induced reductions in renal perfusion pressure. These renal hemodynamic effects are unique when compared with actions of previously studied renal vasodilatory agents.

Anesthesia, General↗
PubMed1985

Hormonal regulation of glomerular filtration.

Technological advances within the last decade now permit examination of the effects of various vasoactive substances on glomerular hemodynamics and the filtration process. By modulating the vasomotor tone of the preglomerular and postglomerular arterioles, these substances influence the rate of plasma entering the glomerulus and the pressure within the glomerular capillaries. In addition, hormones appear to influence the permeability of glomerular capillaries by altering the surface area available for filtration.

Angiotensin II↗
PubMed1985

Dietary protein intake conditions the degree of renal vasoconstriction in acute renal failure caused by ureteral obstruction.

Whole kidney inulin (CIn) and PAH (CPAH) clearances were measured after unilateral release of bilateral ureteral obstruction (BUO) of 24-h duration in rats fed for 4 wk isocaloric diets containing either 40% casein (high protein diet) or 6% casein (low protein diet). Values for CIn and CPAH were markedly depressed in both groups but to a greater extent in high protein-fed rats, averaging less than 60% of values measured in low protein-fed animals. Captopril, an inhibitor of the angiotensin I converting enzyme, increased CIn and CPAH markedly but comparably in high or low protein fed rats. Micropuncture studies performed after unilateral release of BUO in another group of rats fed a high or a low protein diet revealed lower levels of glomerular plasma flow rate (QA) and single nephron glomerular filtration rate (SNGFR) in rats fed a high protein diet. Values for renal arteriolar resistances were nearly twofold in high as compared with low protein-fed animals. Infusion of OKY-1581, an inhibitor of thromboxane A2 synthetase, increased both QA and SNGFR, decreased arteriolar resistances, and increased glomerular capillary ultrafiltration coefficient in high but not in low protein-fed rats. Urinary thromboxane B2 excretion per milliliter of GFR was greater in rats fed a high protein diet than in those fed a low protein diet after release of BUO but not in normal rats. In normal rats infusion of OKY-1581 did not increase CIn or CPAH.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1985

Mechanism of preservation of glomerular perfusion and filtration during acute extracellular fluid volume depletion. Importance of intrarenal vasopressin-prostaglandin interaction for protecting kidneys from constrictor action of vasopressin.

Glomerular circulatory dynamics were assessed in 60 adult anesthetized rats, which were either deprived or not deprived of water for 24-48 h. Water-deprived rats (n = 21) were characterized by a depressed level of single nephron glomerular filtration rate (SNGFR) when compared with nonwater-deprived controls (n = 8) (23.2 +/- 1.3 vs. 44.8 +/- 4.1 nl/min). This was primarily due to decreased glomerular plasma flow rate (71 +/- 5 vs. 169 +/- 23 nl/min) and glomerular capillary ultrafiltration coefficient (0.028 +/- 0.003 vs. 0.087 +/- 0.011 nl/[s . mmHg]). Infusion of saralasin to these water-deprived rats resulted in significant increases in plasma flow rate and ultrafiltration coefficient, and decline in arteriolar resistances. Consequently, SNGFR increased by approximately 50% from pre-saralasin levels. When water-deprived saralasin-treated rats were given a specific antagonist to the vascular action of arginine vasopressin (AVP), d(CH2)5Tyr(Me)AVP, a fall in systemic blood pressure occurred, on average from 102 +/- 5 to 80 +/- 5 mmHg, unaccompanied by dilation of renal arterioles, so that both plasma flow rate (129 +/- 8 vs. 85 +/- 13 nl/min) and SNGFR (31.0 +/- 2.9 vs. 18.2 +/- 4.4 nl/min) decreased. This more selective extrarenal constrictor action of AVP was further documented in additional studies in which cardiac output and whole kidney blood flow rate were simultaneously measured. In water-diuretic rats, administration of a moderately pressor dose of AVP (4 mU/kg per min) resulted in a significant rise in kidney blood flow rate (from 8.8 +/- 1.2 to 9.6 +/- 1.3 ml/min). The higher kidney blood flow rate occurred despite a fall in cardiac output (from 111 +/- 7 to 98 +/- 9 ml/min), and was associated with a significant increase in the ratio of systemic vascular to renal vascular resistance (on average from 0.083 +/- 0.014 to 0.106 +/- 0.019). Furthermore, infusion of d(CH2)5Tyr(Me)AVP to water-deprived animals (n = 6) to antagonize endogenous AVP resulted in systemic but not renal vasodilation, so that kidney blood flow rate fell (by approximately 30%), as did systemic-to-renal resistance ratio (by approximately 30%). When the above two experiments were repeated in indomethacin-treated animals, exogenous AVP administration in water-diuretic rats (n = 6) and antagonism of endogenous AVP in water-deprived rats (n = 7) caused, respectively, parallel constriction and dilation in systemic and renal vasculatures. The net effect was unaltered systemic to renal vascular resistance ratio in both cases. These results indicate that (1) unlike angiotensin II, AVP maintains glomerular perfusion and filtration in acute extracellular fluid volume depletion by a more selective constriction of the extrarenal vasculature. (2) The relative renal insensitivity to the vasoconstrictor action of AVP appears to be due to an AVP-induced release of a potent renal vasodilator, sensitive to indomethacin, presumably prostaglandins.

Animals↗
PubMed1985

Role of renal sympathetic nerves in mediating hypoperfusion of renal cortical microcirculation in experimental congestive heart failure and acute extracellular fluid volume depletion.

To evaluate the pathophysiologic importance of renal nerves in regulating the renal vasomotor tone, we measured several parameters of renal cortical microcirculation before and after acute renal denervation (DNx) in the following three groups of anesthetized Munich-Wistar rats: (group 1) congestive heart failure after surgically induced myocardial infarction (n = 10), (group 2) acute extracellular fluid volume depletion after deprivation of drinking water for 48 h (n = 8), and (group 3) sham or nontreated controls (n = 6). In the myocardial-infarcted rats, DNx led to a uniform increase in glomerular plasma flow rate of, on average, 36%. Single nephron glomerular filtration rate of myocardial-infarcted rats also increased despite a reduction in glomerular capillary hydraulic pressure. These changes were associated with a fall in arteriolar resistances, particularly in the efferent arteriole. The glomerular capillary ultrafiltration coefficient rose in all but one myocardial-infarcted animal. A similar hemodynamic pattern was seen after DNx in water-deprived animals. In every water-deprived animal, glomerular plasma flow rate and single nephron GFR increased on average by 28 and 14%, respectively. Again, afferent and efferent arteriolar resistances decreased significantly. Furthermore, the ultrafiltration coefficient increased uniformly and substantially with DNx. To ascertain the potential importance of the interaction between the renal nerves and angiotensin II in these circumstances, we compared the renal cortical hemodynamics in additional groups of water-deprived rats (group 4) after DNx (n = 15), (group 5) during inhibition of angiotensin II with saralasin (n = 15), and (group 6) during treatment with both saralasin and DNx (n = 15). No appreciable difference was detected between group 4 vs. 6. In contrast, substantial differences were noted between group 5 vs. 6: on average, the glomerular plasma flow rate was 26% higher and the afferent and efferent arteriolar resistances 25% and 27% lower, respectively, in group 6. These observations provide direct evidence to indicate pathophysiologic importance of renal nerves in the profound intrarenal circulatory adjustments in prerenal circulatory impairment. The vasoconstrictive effects of renal nerves appear to be mediated in part by their stimulatory influence on angiotensin II release and their direct constrictor actions on pre- and post-glomerular vessels as well.

Adrenergic Fibers↗
PubMed1985

Alteration in phospholipid content of lung of adult rats treated with methylprednisolone of high doses.

The effect of methylprednisolone (MP) of high dosage on not only surfactant lipids but also other phospholipid components of adult rat lungs was studied. In spite of the decrease in body weight after one and two intraperitoneal injections of MP of 50 and 100 mg/kg, the increase in content of phospholipids of post-lavaged lung tissue, alveolar white layer, and alveolar macrophages occurred. Although the phospholipid content in the lung tissue and white layer started to decrease by following MP treatment of higher doses, its amount in the white layer and macrophages continued to increase by 25 mg/kg of MP. These changes in the phospholipid content with MP treatment was mainly a consequence of the changes in the content of phosphatidylcholine, especially disaturated phosphatidylcholine, as a main component of lung surfactant. The changes in percentages of other phospholipid components, except for phosphatidylglycerol among total phospholipid in the white layer were not significant. Changes in the content and composition of phospholipid of the isolated epithelial type II cells from adult rat lung after one and two injections of MP (50 mg/kg) were similar to those shown in the lung tissue. Our results indicate that, in the adult rat lung, not only the biosynthesis of phospholipid including surfactant lipids but also its secretion into alveolar space are greatly stimulated by administration of MP of high doses.

Animals↗
PubMed1984

Glomerular actions of angiotensin II.

An abundance of evidence suggests that glomerular ultrafiltration is significantly influenced by alterations in circulating or local concentrations of a variety of vasoactive substances. Angiotensin II regulates whole kidney glomerular filtration rate by influencing one or more of the determinants of single nephron glomerular filtration rate, particularly the ultrafiltration coefficient and glomerular plasma flow rate. The glomerular mesangial cell may be an important target for angiotensin II by virtue of its ability to contract and thereby reduce glomerular capillary surface area and ultrafiltration coefficient. These control mechanisms are not only important under physiologic conditions but they may also be activated by a variety of insults and thereby contribute to the decrease in glomerular filtration rate observed in a broad spectrum of renal disease.

Angiotensin II↗