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Biomedical subjects

I Ichikawa

Publications and source records attributed to I Ichikawa.

At least 145 records · Page 8Linked to original sources
PubMed1984

Comparative effects of propranolol and nadolol on renal blood flow in normal rats and rats with congestive heart failure.

Mean arterial blood pressure (MAP), heart rate (HR), renal blood flow (RBF), and renal vascular resistance (RVR) were determined before and during an infusion of propranolol (18 mg/kg/hr) or nadolol (30 mg/kg/hr) in anesthetized Munich-Wistar rats with normal cardiac function. Eight rats treated with propranolol had significant reductions in MAP (110 to 98 mm Hg; p less than 0.05) and HR (316 to 242 bpm; p less than 0.01), accompanied by a 24% decrease in RBF (5.9 to 4.5 ml/min; p less than 0.05) and a 22% increase in RVR (19.4 to 23.7 mm Hg/ml/min; p less than 0.05). Although nadolol also reduced MAP (104 to 93 mm Hg; p less than 0.01) and HR (315 to 268 bpm; p less than 0.05) in eight other rats, RBF and RVR remained unchanged from baseline levels. Thus, despite similar decrements in MAP and HR, propranolol decreased renal perfusion, whereas nadolol maintained it in animals with noninfarcted myocardium. These parameters were also evaluated in rats with congestive heart failure induced by myocardial infarction at least 3 weeks prior to their receiving either propranolol (18 mg/kg/hr; n = 6) or nadolol (30 mg/kg/hr; n = 6). In the basal state, rats with congestive heart failure had significantly (p less than 0.05) lower MAP, HR, and RBF and higher (p less than 0.01) RVR compared with control rats. Propranolol and nadolol induced comparable falls (p less than 0.05) in MAP and HR. Whereas RBF tended to fall with propranolol (3.3 to 2.4 ml/min), renal perfusion was well maintained with nadolol (3.4 to 3.8 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1984

Respiratory effects of intermittent exposure to ozone of rats.

Intermittent exposures of rats to ozone (O3) of 1 and 0.5 ppm were performed. Flow resistance of the lungs left in situ in the chest cavity opened after the sacrifice was measured at different levels of elastic pressure, and it was shown that daily 3-hr exposures to 1 ppm O3 for 30 consecutive days mainly produced increased resistance of more-central airways, while daily 6-hr exposures to 0.5 ppm O3 for 60 consecutive days mainly increased the resistance of peripheral airways. Morphological changes of the lungs caused by both exposures were in general similar in nature, but differences in secretion were noticed: it was more evident in larger to middle-sized bronchi in the animals intermittently exposed to 1 ppm O3, but more evident in the peripheral airway region in the animals intermittently exposed to 0.5 ppm O3. No change in the pulmonary static volume-pressure curve, indicative of the altered retractive forces of alveoli, was observed in both exposures, although a slight reduction in lung distensibility was suggested.

Airway Resistance↗
PubMed1984

Pulmonary functions of rats trained with mild exercise.

The purpose of the present study was to determine if lung function is modified by physical exercise in male and female rats. The animals were subjected to a running program for 5 weeks. At the termination of the program period, the running rats (R) had body weight smaller than the sedentary control rats (S). In male rats, the weights of lung, heart and adrenal glands, which were corrected with body weight, were larger in the R than in the S, and the absolute weight of adrenal glands also increased in the R. The rates of peak flow and maximum expiratory flow at 50% total lung capacity, which were corrected with either body weight, lung weight or total lung capacity, increased in the R. Because of no significant change in the flow resistance and compliance of the lungs, the increases in the rates of these expiratory flows might have been due to increased airway rigidity caused by some mechanisms relating to exercise stimuli. In female rats, on the other hand, the above changes in the R were little or less.

Animals↗
PubMed1984

Physiologic basis for the maintenance of glomerulotubular balance in young growing rats.

To examine the physiologic basis of preservation of glomerulotubular balance in young growing animals, we measured the various determinants for fluid transfer across the glomerular and postglomerular capillaries in young (approximately 40 days, N = 8) and adult (N = 8) male Munich-Wistar rats under mild volume expansion. The single nephron (SN) GFR increased by approximately 2.5-fold from young to adult animals. The increase in SNGFR was due to marked rises in both glomerular plasma flow rate (QA) and ultrafiltration coefficient (Kf). The increase in QA was associated with a nearly 60% reduction in afferent and efferent arteriolar resistances. As with SNGFR, the absolute proximal reabsorption rate (APR) increased by some 2.5-fold, indicating preservation of perfect glomerulotubular balance. Of the factors determining peritubular capillary uptake of APR, the mean oncotic pressure difference across the peritubular capillary was similar in young and adult animals. The mean hydraulic pressure difference was also comparable in the two groups. By contrast, the peritubular capillary reabsorption coefficient (Kr) rose markedly and accounted entirely for the increase in peritubular capillary uptake of APR during growth. These results obtained under mild volume expansion indicate that the maintenance of glomerulotubular balance in the growing rat requires harmonious growth of renal microcirculation, that is, glomerular capillary (Kf) and arteriolar (QA) maturation balances the development of peritubular capillary (Kr).

Absorption↗
PubMed1984

Role of angiotensin II in the altered renal function of congestive heart failure.

Glomerular and tubule functions were assessed by micropuncture in rats with extensive myocardial infarction produced by ligation of the left coronary artery 4 weeks prior to study. When compared to sham-operated control rats, rats with myocardial infarction involving 40 +/- 4% of the left ventricular circumference had lower mean arterial pressure (96 +/- 5 vs. 122 +/- 4 mm Hg, P less than 0.005), and higher left ventricular end-diastolic pressure (24 +/- 3 vs. 5 +/- 0 mm Hg, P less than 0.001). Renal cortical microcirculatory dynamics of rats with myocardial infarction were characterized by reduced glomerular plasma flow rate (75 +/- 8 vs. 165 +/- 17 nl/min, P less than 0.005), but a proportionately lesser decline in single nephron glomerular filtration rate (28.0 +/- 2.8 vs. 41.7 +/- 3.1 nl/min, P less than 0.025), accounting for the observed rise in single nephron filtration fraction (0.38 +/- 0.02 vs. 0.25 +/- 0.02, P less than 0.005). These renal hemodynamic alterations in myocardial-infarcted rats were accompanied by a striking elevation in efferent arteriolar resistance (3.03 +/- 0.31 vs. 0.95 +/- 0.16 X 10(10) dyn X sec X cm-5, P less than 0.001). In addition, fractional proximal fluid reabsorption, assessed by end-proximal tubule fluid-to-plasma inulin concentration ratio, was elevated (2.21 +/- 0.12 vs. 1.64 +/- 0.09, P less than 0.025). The intravenous infusion of teprotide, an angiotensin I-converting enzyme inhibitor, led to the return of glomerular plasma flow rate, single nephron filtration fraction, single nephron glomerular filtration rate, efferent arteriolar resistance, and fractional proximal fluid reabsorption in myocardial-infarcted rats to, or toward, the levels found in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1983

Hormonal modulation of glomerular function.

Glomeruli contain receptors for many hormones. Binding of angiotensin II (ANG II) or antidiuretic hormone (ADH) to glomerular mesangial cells elicits a contractile response. Other hormones induce synthesis of cyclic nucleotides (cAMP, cGMP). Glomeruli also synthesize several prostaglandins, renin, and ANG II. Micropuncture studies in Munich-Wistar rats have examined the effects of vasoactive drugs and hormones on the filtration process. Several vasodilators increase renal plasma flow in the dog and rat, but GFR remains relatively unchanged due to an offsetting fall in the ultrafiltration coefficient (Kf). Vasoconstrictor substances such as ANG II and norepinephrine cause declines in renal plasma flow and Kf, but GFR remains constant due to an increase in the transcapillary hydraulic pressure gradient. Antidiuretic peptides and parathyroid hormone also reduce Kf. Glomerular mesangial cells may regulate Kf by contracting and reducing glomerular capillary surface area. ANG II and ADH directly stimulate mesangial cell contraction in vitro. Other hormones appear to cause contraction by inducing local ANG II synthesis. These hormonal pathways are implicated in the pathogenesis of altered glomerular function in diverse forms of renal injury.

Animals↗
PubMed1983

Effector loci for renal nerve control of cortical microcirculation.

To determine the effector loci for renal neural vasomotor control, we performed micropuncture measurements before or after renal nerve stimulation and during low- (0.5-1.5 Hz) (LFS) or high- (3-5 Hz) (HFS) frequency nerve stimulation in Munich-Wistar rats. In response to HFS, single nephron glomerular filtration rate decreased on average from 24.1 +/- 4.1 to 10.4 +/- 2.3 nl/min. Although mean glomerular transcapillary hydraulic pressure difference remained essentially constant, HFS led to a marked fall in glomerular plasma flow rate (71.3 +/- 0.9 to 44.1 +/- 10.4 nl/min). The latter was associated with significant increase in both afferent (RA) and efferent (RE) arteriolar resistance, on average by more than twofold. Because of this profound arteriolar constriction, early peritubular capillary hydraulic pressure (PEA) fell markedly during HFS (mean: 19.1 +/- 1.4 vs. 13.2 +/- 1.4 mmHg). The ultrafiltration coefficient (Kf) also decreased significantly, on average from 0.055 +/- 0.014 to 0.015 +/- 0.002 nl/(s . mmHg) with HFS. By contrast, LFS affected these indices to a much lesser and more variable degree although the marked decline in PEA was again demonstrated. Despite this decrease in postglomerular capillary hydraulic pressure, absolute proximal tubule fluid reabsorption (APR) failed to change in some animals and decreased slightly in others. Analysis of the Starling forces acting across the peritubular capillaries showed that due largely to a uniform decrease in mean peritubular capillary hydraulic pressure, mean net reabsorption pressure (Pr) rose substantially and significantly, on average by more than 5 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Relative contribution of vasopressin and angiotensin II to the altered renal microcirculatory dynamics in two-kidney Goldblatt hypertension.

The renal microcirculation was assessed in non-clipped kidneys of 23 Munich-Wistar rats with two-kidney one-clip Goldblatt hypertension. Four weeks after placement of a renal arterial clip, mean systemic arterial pressure averaged 163 +/- 5 mm Hg in hypertensive rats as compared to 108 +/- 2 in sham-operated controls (n = 6 rats). Non-clipped kidneys in hypertensive rats were characterized by higher glomerular capillary hydraulic pressures, single nephron glomerular filtration rate, and afferent arteriolar resistance. The glomerular capillary ultrafiltration coefficient was significantly reduced in hypertensive rats. In 10 of these rats, intravenous infusion of the angiotensin antagonist, saralasin, or the converting enzyme inhibitor, SQ20881, led to significant reductions in systemic arterial pressure and in afferent and efferent arteriolar resistance, on average by 8 +/- 3%, 15 +/- 4%, 28 +/- 5%, respectively. These changes were associated with significant increase in glomerular plasma flow, while ultrafiltration coefficient remained unaffected. In the presence of saralasin or SQ20881, infusion of a specific antagonist of the vascular action of arginine vasopressin led to significant systemic but not renal vasodilation. Thus, whereas systemic arterial pressure fell further, on average by 23 +/- 2%, renal arteriolar resistance remained constant, resulting in marked reduction in glomerular capillary hydraulic pressures (by 18 +/- 2%) and glomerular plasma flow rate (by 28 +/- 10%). Because of these pronounced reductions in glomerular pressures and flows induced by vasopressin antagonist, single nephron glomerular filtration rate fell markedly in hypertensive rats (by 34 +/- 6%) despite normalization of ultrafiltration coefficient. When hypertensive rats (n = 7) were treated with vasopressin antagonist alone, a modest fall in systemic arterial pressure was again observed in the absence of changes in renal arteriolar resistance. Due to this selective extrarenal vasodilatory action of vasopressin antagonist, glomerular capillary hydraulic pressure, plasma flow rate, and single nephron glomerular filtration rate again fell markedly. When these vasopressin antagonist pre-treated hypertensive rats were given saralasin or SQ20881, marked reductions in renal arteriolar resistance were observed in association with a significant increase in glomerular plasma flow rate. These observations made during acute inhibition of angiotensin II and vasopressin indicate that both of these vasopressin hormones may play important roles in maintaining systemic hypertension in hypertensive rat. By virtue of its preferential constrictor effects on extrarenal rather than renal vasculature vasopressin serves to maintain high glomerular pressures and flows in the non-clipped kidney of Goldblatt hypertensive rats.

Angiotensin II↗
PubMed1983

Role for intrarenal mechanisms in the impaired salt excretion of experimental nephrotic syndrome.

A unilateral model of puromycin aminonucleoside (PAN)-induced albuminuria was produced in Munich-Wistar rats to examine the mechanisms responsible for renal salt retention. 2 wk after selective perfusion of left kidneys with PAN (n = 8 rats) or isotonic saline (control, n = 7 rats), increases in albumin excretion and decreases in sodium excretion were demonstrated in PAN-perfused but not in nonperfused kidneys of PAN-treated rats although systemic plasma protein concentration remained at control level. Total kidney glomerular filtration rate (GFR) and superficial single nephron (SN) GFR were also reduced selectively in PAN-perfused kidneys, on average by approximately 30%, due primarily to a marked decline in the glomerular capillary ultrafiltration coefficient (Kf), which was also confined to PAN-perfused kidneys. Values for absolute proximal reabsorption (APR) were also selectively depressed in PAN-perfused kidneys, in keeping with a similarly selective decline in peritubular capillary oncotic pressure measured in these kidneys, the latter also a consequence of the fall in Kf. In a separate group of seven PAN-treated rats, however, no differences were detected between PAN-perfused and nonperfused kidneys in the absolute amount of sodium reaching the early (0.77 +/- 0.09 neq/min vs. 0.74 +/- 0.08, P greater than 0.40) and late portions of superficial distal tubules (0.31 +/- 0.02) neq/min vs. 0.32 +/- 0.05, P greater than 0.50), despite the lesser filtered load of sodium in PAN-perfused kidneys. Suppressed sodium reabsorption in both proximal convoluted tubules and short loops of Henle of PAN-perfused kidneys contributed to this equalization of sodium delivery rates to the late distal tubule, as did comparable reabsorption along distal convolutions. In two additional groups of PAN-treated rats, infusion of saralasin (0.3 mg/kg per h, i.v.) led to substantial increases in total kidney GFR and SNGFR in PAN-perfused but not in nonperfused kidneys. Despite these increases in total and SNGFR, urinary sodium excretion by PAN-perfused kidneys remained at a level far below that for nonperfused kidneys, again indicating that the antinatriuresis characterizing the PAN-perfused kidney is due to alterations in sodium handling by the tubules rather than changes in GFR. These results therefore indicate (a) that reductions in Kf and depressed sodium reabsorption by proximal tubules and Henle's loop segments in this model are brought about by intrarenal rather than circulating or systemic factors, and (b) assuming that superficial nephrons are representative of the entire nephron population, renal salt retention in this model is due primarily to intrarenal factor(s) acting beyond the distal convolution.

Animals↗
PubMed1983

Blood flow dependence of postglomerular fluid transfer and glomerulotubular balance.

The rate of blood flow entering a capillary network can, in some vascular systems, regulate capillary surface area and the rate of fluid and solute transfer. To determine whether such a mechanism exists in the renal peritubular capillary, we performed micropuncture studies in 28 rats during relatively low and high efferent arteriolar blood flow (EABF). High EABF was achieved by intravenous infusion of isoncotic plasma (group 1: from 120 +/- 11 to 301 +/- 49 nl/min [+/- SE]); whole blood with high hematocrit (approximately 75 vol %) (group 2: from 141 +/- 14 to 252 +/- 31 nl/min); or acetylcholine (group 3: from 193 +/- 20 to 266 +/- 26 nl/min). In group 1 rats, plasma infusion caused an increase in single nephron glomerular filtration rate (SNGFR), on average, from 23.2 +/- 2.4 to 45.2 +/- 3.9 nl/min, owing primarily to increased glomerular plasma flow rate (from 63 +/- 5 to 210 +/- 21 nl/min). The rate of fluid uptake by the peritubular capillary, assessed by the absolute rate of proximal fluid reabsorption (APR), also rose significantly, on average from 10.5 +/- 1.2 to 17.5 +/- 2.4 nl/min. This rise in APR was associated with near constancy in mean transcapillary hydraulic (delta Pc) and oncotic (delta IIc) pressure differences, and was therefore attributed to a significant increase in peritubular capillary reabsorption coefficient (Kr), with the mean from 0.017 +/- 0.003 to 0.030 +/- 0.005 nl/(s . mmHg). In group 2 rats, high hematocrit blood infusion led to a significant rise in APR; on average, from 10.7 +/- 0.7 to 15.0 +/- 1.2 nl/min, without changing SNGFR. This rise in APR occurred despite unfavorable changes in the physical forces, namely a significant increase in delta Pc and constancy in delta IIc. Instead, an increase in EABF was again associated with a significant rise in Kr (on average, from 0.016 +/- 0.002 to 0.030 +/- 0.06 nl/[s . mmHg]), which accounted entirely for the rise in APR, independently of SNGFR. In group 3 rats, in which an increase of EABF was induced pharmacologically with acetylcholine, a rise in EABF was also accompanied by a significant increase in Kr, on average, from 0.019 +/- 0.002 to 0.026 +/- 0.004 nl/(s . mmHg). The results indicate that: (a) Kr is modulated by EABF. (b) In view of plasma flow dependence of GFR, blood flow dependence of Kr and APR provides an important basis for glomerulotubular balance.

Absorption↗
PubMed1983

Glomerular mesangium as an effector locus for the tubuloglomerular feedback system and renal sympathetic innervation.

To define the effector loci for the tubuloglomerular feedback system, the determinants of the single-nephron glomerular filtration rate (SNGFR) were assessed in Munich-Wistar rats by direct glomerular puncture during perfusion of Henle's loop with isotonic Ringer's solution at rates of 0 and 40 nl/min. At the higher flow rate, SNGFR averaged only approximately 65% that measured during the lower flow rate. Whereas mean glomerular capillary hydraulic pressure was unaffected, both glomerular plasma flow rate and ultrafiltration coefficient Kf were found to decrease significantly in response to increase in loop perfusion rate, thereby accounting for the measured reduction in SNGFR. These changes were associated with increased afferent (RA) and efferent (RE) arteriolar resistances. Based on the close anatomic contact between mesangial cells and these arterioles, a single effector mechanism channeled through mesangial contractility is suggested to account for the observed reduction in Kf and increase in RA and RE. Mesangial contractility appears to be under sympathetic nerve control. In our recent micropuncture study with Munich-Wistar rats, a marked reduction in SNGFR was observed during high-frequency stimulation (5 Hz) of the renal nerve. This reduction in SNGFR was accompanied by a marked fall in Kf and increase in RA and RE. When kidneys were perfusion-fixed during high-frequency stimulation, a marked reduction in the number of open channels was demonstrated together with marked narrowing of afferent and efferent arterioles. These observations are consistent with the view that sympathetic innervation of mesangium may modulate GFR through its ability to regulate mesangial contractility.

Animals↗
PubMed1982

Effect of short-term exposure to ozone on the lecithin metabolism of rat lung.

The effect of short-term inhalation of ozone (O3) on the content and metabolism of phospholipids, particularly lecithin (PC), in rat lung was studied. The PC level increased slightly, but significantly, in the lung of rats exposed to 2 ppm O3 for 3 h. However, the PC level remained within the control level following the exposure to 2.5 and 5 ppm of O3 for 3 h, while the lysolecithin (LysoPC) content greatly increased. The incorporation of [32P]orthophosphate (32Pi) and [14C]palmitic acid into PC in the lung slices obtained from the animals tended to increase following the exposure to 2 ppm for 3 h, but decreased following the exposure to O3 above 2.5 ppm for 3 h. On the other hand, the radioactivity of 32Pi in LysoPC of lung from the rats exposed to O3 above 2.5 ppm was significantly greater than that from the control. Such changes in the content of PC or LysoPC and in the incorporation of labeled precursors into them may be explained, at least in part, by the combination of the presently and previously observed changes in the activities of enzymes participating in PC metabolism pathway as follows: (1) the significant stimulation in the activity of LysoPC acyltransferase (LysoPC ATF), which can transfer fatty acids onto LysoPC, for palmitic acid at an earlier stage of the exposure to O3 at 2 and 2.5 ppm; (2) the depression in the activities of this enzyme and another ATF-LysoPC-LysoPC ATF, which can synthesize one molecule of disaturated PC from two moles of saturated-LysoPC-by increasing the O3 exposure time; and (3) the stimulation in the phospholipase A2 activity in the lung of rats exposed to 2 ppm of O3 for 6 h.

Acyltransferases↗
PubMed1982

Evidence for altered glomerular hemodynamics during acute nephron obstruction.

The stop-flow technique has been used to estimate mean glomerular capillary hydraulic pressure (PGC). This technique involves complete obstruction of fluid flow in single proximal tubules, thereby altering the formation of glomerular filtrate as well as the delivery of fluid to more distal segments of the same nephron. To determine whether tubule obstruction affects PGC, pressures were measured in capillaries of accessible glomeruli before and during proximal tubule obstruction in hydropenic Munich-Wistar rats. The results were compared with estimates of PGC obtained for these same glomeruli by the stop-flow technique. When glomerular filtration was unhindered, blockade of fluid flow into the loop of Henle did not alter directly measured PGC values. When glomerular filtration was stopped by proximal tubule obstruction, directly measured PGC values increased by approximately 7 mmHg. Stopping glomerular filtration also increased postglomerular capillary hydraulic pressure, suggesting that acute single nephron obstruction and cessation of filtration substantially affects these pressures by diverting fluid to the postglomerular capillary bed. Indirect stop-flow estimates of PGC did not differ from direct measurements of PGC in the same glomeruli during stopped flow. Thus, in the normal hydropenic condition, stop-flow estimates of PGC accurately measure PGC. However, the PGC value prevailing under the stop-flow condition is substantially elevated over the PGC existing when filtration is proceeding normally.

Animals↗