Renal hypertension prevents run training modification of cardiomyocyte diastolic Ca2+ regulation in male rats

2001 ◽  
Vol 90 (6) ◽  
pp. 2063-2069 ◽  
Author(s):  
Bradley M. Palmer ◽  
Joshua M. Lynch ◽  
Steven M. Snyder ◽  
Russell L. Moore
Keyword(s):  
Renal Hypertension ◽  
Left Ventricular ◽  
Male Rats ◽  
Left Renal Artery ◽  
Sham Operation ◽  
Fischer 344 Rats ◽  
Efflux Rate ◽  
Fischer 344 ◽  
Regulation Mechanisms ◽  
Electrical Pacing

The combined effects of endurance run training and renal hypertension on cytosolic Ca2+ concentration ([Ca2+]c) dynamics and Na+-dependent Ca2+ regulation in rat left ventricular cardiomyocytes were examined. Male Fischer 344 rats underwent stenosis of the left renal artery [hypertensive (Ht), n = 18] or a sham operation [normotensive (Nt), n = 20]. One-half of the rats from each group were treadmill trained for >16 wk. Cardiomyocyte fura 2 fluorescence ratio transients were recorded for 7 min during electrical pacing at 0.5 Hz, 2 mM extracellular Ca2+ concentration, and 29°C. The rate of [Ca2+]c decline was not changed by run training in the Nt group but was reduced in the Ht group. At 7 min, cardiomyocytes were exposed to 10 mM caffeine in the absence of Na+ and Ca2+, which triggered sarcoplasmic reticular Ca2+ release and suppressed Ca2+efflux via Na+/Ca2+ exchanger. External Na+ was then added, and Na+-dependent Ca2+ efflux rate was recorded. Treadmill training significantly enhanced Na+-dependent Ca2+efflux rate under these conditions in the Nt group but not in the Ht group. These data provide evidence that renal hypertension prevents the normal run training-induced modifications in diastolic [Ca2+]c regulation mechanisms, including Na+/Ca2+ exchanger.

Mild renal hypertension alters run training effects on the frequency response of rat cardiomyocyte mechanics

2003 ◽  
Vol 95 (5) ◽  
pp. 1799-1807 ◽  
Author(s):  
Bradley M. Palmer ◽  
Eric A. Mokelke ◽  
Anne M. Thayer ◽  
Russell L. Moore
Keyword(s):  
Frequency Response ◽  
Calcium Concentration ◽  
Renal Hypertension ◽  
Left Renal Artery ◽  
Sham Operation ◽  
Fischer 344 Rats ◽  
Shortening Velocity ◽  
Fischer 344 ◽  
Relaxation Parameters ◽  
Cardiomyocyte Mechanics

We examined the effects of run training on the frequency dependence of cardiomyocyte mechanics and intracellular calcium concentration ([Ca2+]i) dynamics in rats with mild renal hypertension. Male Fischer 344 rats aged 2–3 mo underwent a sham operation or stenosis of the left renal artery, which increased systolic blood pressure 20–30 mmHg. Half of the rats in each group underwent treadmill run training for >16 wk. Isolated cardiomyocytes were paced at 1.0 and 0.2 Hz in 2 mM external Ca2+ concentration at 29°C. Under these conditions, negative frequency responses, i.e., decreased value with increased frequency, were recorded for peak shortening, shortening velocity, and the integral of the [Ca2+]i transient in both groups. Run training amplified the negative frequency response for the integral of the [Ca2+]i transient in both groups, but it amplified the negative frequency response for the shortening dynamics only in the normotensive sham-operated and not in the hypertensive rats. These results, as well as others for relaxation parameters, suggest that renal hypertension altered the effects of run training on the frequency response for cardiomyocyte contractile apparatus and/or passive mechanical properties, which respond to [Ca2+]i.

Toxic effects of inhaled DMMP on the kidneys of Fischer-344 rats

1987 ◽  
Vol 45 ◽  
pp. 880-881
Author(s):  
D.R. Mattie ◽  
C.J. Hixson
Keyword(s):  
Left Kidney ◽  
Inhalation Exposure ◽  
Electron Microscopic Examination ◽  
Exposure Period ◽  
Male Rats ◽  
Continuous Exposure ◽  
Fischer 344 Rats ◽  
Electron Microscopic ◽  
Thin Sections ◽  
Fischer 344

Dimethylmethylphosphonate (DMMP) is a simple organophosphate used industrially as a flame retardant and to lower viscosity in polyester and epoxy resins. The military considered the use of DMMP as a nerve gas simulant. Since military use of DMMP involved exposure by inhalation, there was a need for a subchronic inhalation exposure to DMMP to fully investigate its toxic potential.Male Fischer-344 rats were exposed to 25 ppm or 250 ppm DMMP vapor on a continuous basis for 90 days. An equal number of control rats were sham-exposed. Following the 90-day continuous exposure period, 15 male rats were sacrificed from each group. Two rats from each group had the left kidney perfused for electron microscopic examination. The kidneys were perfused from a height of 150 cm water with 1% glutaraldehyde in Sorensen's 0.1M phosphate buffer pH 7.2. An additional kidney was taken from a rat in each group and fixed by immersion in 2.5% glutaraldehyde and 2% paraformaldehyde in 0.1M cacodylate buffer pH 7.4. A portion of the 9 kidneys collected for electron microscopy were processed into Epon 812. Thin sections, stained with uranyl acetate and lead citrate, were examined with a JEOL 100B Transmission Electron Microscope. Microvilli height was measured on photographs of the cells of proximal tubules. This data, along with morphologic features of the cells, allows the proximal convoluted tubules (PCT) to be identified as being S1, S2, or S3 segment PCT.

Time course of hemodynamic changes in rats with healed severe myocardial infarction

1989 ◽  
Vol 257 (1) ◽  
pp. H289-H296 ◽  
Author(s):  
A. DeFelice ◽  
R. Frering ◽  
P. Horan
Keyword(s):  
Myocardial Infarction ◽  
Blood Flow ◽  
Cardiac Output ◽  
Diastolic Pressure ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Male Rats ◽  
Coronary Artery Ligation ◽  
Sham Operation ◽  
Functional Changes

Male rats were monitored for 8 mo after severe myocardial infarction (MI) to chronicle hemodynamic and left ventricular (LV) functional changes. Blood pressure (BP), heart rate (HR), cardiac output index (CO), regional blood flow, and systemic vascular resistance (SVR) were measured with catheters and radiolabeled microspheres at 4, 7, 10, 20, and 35 wk after coronary artery ligation (n = 10–16/group) or sham operation (control; n = 9–14/group). At 4 wk, 43 +/- 1% of the LV circumference was scarred, peak LV BP, LV dP/dtmax, mean BP, SVR, and HR were 11–38% less than control (P less than 0.05), and LV end-diastolic pressure (LVEDP) was increased by 313% (P less than 0.05). Mean BP, LVEDP, LVBP, and LV dP/dtmax did not further deviate after 4 wk. However, CO and SVR changed progressively and were 67 and 33%, respectively, of control by 35 wk (P less than 0.05) when blood flow to stomach, small intestine, and kidney was 55, 38, and 27% of control. Lung and heart weights were significantly increased by 148 and 22% at 4 wk, and remained elevated, and lung dry weight-to-wet weight ratio was reduced at 7 and 10 wk. Thus the trajectory of rats with healed severe MI reflects progressive cardiac decompensation, cardiac output redistribution, and terminal heart failure.

Central neurotoxicity induced by subchronic exposure to 2,4-pentanedione vapour

1995 ◽  
Vol 14 (8) ◽  
pp. 662-671 ◽  
Author(s):  
RH Garman ◽  
DE Dodd ◽  
B. Ballantyne
Keyword(s):  
Electron Microscopy ◽  
Vestibular Nuclei ◽  
Brain Lesions ◽  
Female Rats ◽  
Male Rats ◽  
Fischer 344 Rats ◽  
Male And Female ◽  
Fischer 344 ◽  
Peripheral Nerve Lesions ◽  
Microscopical Evidence

1 Male and female Fischer 344 rats were exposed to 2,4- pentanedione (2,4-PD) vapour acutely (4 h) at 1265 or 1811 ppm, or for 6 h day-1 , 5 days a week for 14 weeks to 0, 101, 307 or 650 ppm. 2 Mortality occurred during or within a few hours of the acute exposures (10% at 1265 ppm; 70% at 1811 ppm). No animal had gross or microscopic brain lesions. 3 All female rats (20) and 10 of 30 male rats exposed to 650 ppm 2,4-PD vapour died by the 38th study day (29 exposures); there were no subsequent male deaths. Twenty-five of the 30 animals that died, and seven of the 15 males that survived, had light microscopical evidence of degenerative lesions, principally within the caudate/putamen nuclei, nuclei of the cerebellar medulla, and vestibular nuclei. Less frequently involved, in animals that died, were various regions of the cerebral cortex. The early histopathological lesions, seen from the 16th study day (12 exposures) to the 38th study day (28 exposures) were characterised by malacia. When present, lesions in male rats surviving the 14-weeks of 650 ppm 2, 4-PD expo sure were characterised by malacia and gliosis. No peripheral nerve lesions were seen by light or transmis sion electron microscopy. 4 Neither mortality nor neuropathology were seen in rats subchronically exposed to 101 or 307 ppm, 2,4-PD vapour.

Subchronic Studies of Thenyldiamine in Fischer 344 Rats

1990 ◽  
Vol 9 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Carlton D. Jackson ◽  
Gerald M. Cronin ◽  
Theodore W. Stone
Keyword(s):  
Weight Gain ◽  
Physiological Responses ◽  
Clinical Signs ◽  
Male Rats ◽  
Fischer 344 Rats ◽  
Fatty Change ◽  
Significant Treatment ◽  
Fischer 344 ◽  
Free Amine ◽  
Dose Levels

Thenyldiamine, an antihistamine used extensively as a sleep aid, has not been adequately studied for subchronic or chronic toxicity. This report presents the results of subchronic studies of thenyldiamine in the rat. Fischer 344 rats were administered thenyldiamine hydrochloride in their feed at dose levels of 0, 250, 500, 1000, 2000, and 4000 ppm (calculated as free amine) for 14 days or at dose levels of 0, 125, 250, 500, 1000, and 2000 ppm for 90 days. There were no mortalities in either study. Except for decreased weight gain, no significant treatment-related toxicity was observed in the 14-day study. In the 90-day study, 500 ppm and 1000 ppm were the lowest doses responsible for causing a significant decrease in weight gain in females and males, respectively. Clinical signs, gross observations at necropsy, and organ weights in the 90-day study were not remarkable. Histologically, a treatment-related mild fatty change was found in the livers of male rats, but the effect was so mild as to make the significance questionable. Treatment-related changes were also observed in the parotid salivary glands, but the significance of these changes was also questionable in view of the variability of this gland and its recognized physiological responses to antihistamines.

Subchronic Inhalation Toxicity and Neurotoxicity Assessment of Cumene in Fischer 344 Rats

1995 ◽  
Vol 14 (2) ◽  
pp. 129-147 ◽  
Author(s):  
Janette R. Cushman ◽  
James C. Norris ◽  
Darol E. Dodd ◽  
Kenneth I. Darmer ◽  
Carl R. Morris
Keyword(s):  
Body Weight Gain ◽  
Clinical Chemistry ◽  
Recovery Period ◽  
Male Rats ◽  
Inhalation Toxicity ◽  
Fischer 344 Rats ◽  
Auditory Brain Stem Response ◽  
Fischer 344 ◽  
Renal Proximal Tubular ◽  
Functional Observational Battery

Male and female Fischer 344 rats were exposed to cumene vapor at 0, 100, 500, and 1,200 ppm for 6 h per day, 5 days per week, for 13 weeks; a satellite group received a single 6-h exposure. A subsequent 13-week study with a 4-week recovery period was conducted at 0, 50, 100, 500, and 1,200 ppm. Following the single exposure, the functional observational battery was altered at 500 and 1,200 ppm through 6 h postexposure. In the subchronic studies, there were no exposure-related changes in the functional observational battery, auditory brain stem response, brain measurements, or nervous system histopathology. Motor activity decreases seen only in male rats exposed to 500 or 1,200 ppm in the first study were not replicated in the second study. The 500-and/or 1,200-ppm groups showed transient decreases in body weight gain and food consumption, an increase in water consumption, and changes in several hematologic and clinical chemistry parameters. There were no exposure-related ophthalmologic findings or effects on spermatogenesis. Weights of liver, kidneys, and adrenal glands were increased in the 500- and 1,200-ppm groups. Renal proximal tubular cell hypertrophy, hyperplasia, and hyaline drop formation were observed in the male rats at 500 and 1,200 ppm. In conclusion, exposure to cumene vapor resulted in mild toxicity at 1,200 ppm, minimal effects at 500 ppm, and no observable effects at 50 and 100 ppm. Cumene vapor exposure was neither neurotoxic nor ototoxic in these studies.

scholarly journals Mechanical work and energetic analysis of eccentric cardiac remodeling in a volume overload heart failure in rats

2009 ◽  
Vol 296 (4) ◽  
pp. H1117-H1124 ◽  
Author(s):  
Yoshiaki Takewa ◽  
Elie R. Chemaly ◽  
Miyako Takaki ◽  
Li Fan Liang ◽  
Hongwei Jin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Remodeling ◽  
Sham Group ◽  
Group Versus ◽  
Volume Overload ◽  
Left Ventricular ◽  
Mechanical Work ◽  
Energy Utilization ◽  
Male Rats ◽  
Sham Operation

Eccentric cardiac remodeling seen in dilated cardiomyopathy or regurgitant valvular disease is a well-known process of heart failure progression, but its mechanoenergetic profile has not been yet established. We made a volume overload (VO) heart failure model in rats and for the first time investigated left ventricular (LV) mechanical work and energetics in cross-circulated whole heart preparations. Laparotomy was performed in 14 Wistar male rats, and abdominal aortic-inferior vena caval shunt was created in seven rats (VO group). Another seven rats underwent a sham operation without functional shunt (Sham group). LV dimensions changes were followed with weekly transthoracic echocardiography. Three months after surgery, we measured LV pressure and volume and myocardial O2 consumption in isolated heart cross circulation. LV internal dimensions in both systolic and diastolic phases were significantly increased in the VO group versus the Sham group ( P < 0.05). LV pressure was markedly decreased in the VO group versus in the Sham group ( P < 0.05). LV end-systolic pressure-volume relation shifted downward, and myocardial O2 consumption related to Ca2+ handling significantly decreased. The contractile response to Ca2+ infusion was attenuated. Nevertheless, the increase in Ca2+ handling-related O2 consumption per unit change in LV contractility in the VO group was significantly higher than that in the Sham group ( P < 0.05). The levels of sarco(endo)plasmic reticulum Ca2+-ATPase 2a protein were reduced in the VO group ( P < 0.01). In conclusion, VO failing rat hearts had a character of marked contractile dysfunction accompanied with less efficient energy utilization in the Ca2+ handling processes. These results suggest that restoring Ca2+ handling in excitation-contraction coupling would improve the contractility of the myocardium after eccentric cardiac remodeling.

Age-related changes in cardiac structure and function in Fischer 344 × Brown Norway hybrid rats

2006 ◽  
Vol 290 (1) ◽  
pp. H304-H311 ◽  
Author(s):  
Timothy A. Hacker ◽  
Susan H. McKiernan ◽  
Pamela S. Douglas ◽  
Jonathan Wanagat ◽  
Judd M. Aiken
Keyword(s):  
Heart Function ◽  
Weight Ratio ◽  
Volume Density ◽  
Left Ventricular ◽  
Male Rats ◽  
Brown Norway ◽  
Cardiac Structure ◽  
F1 Hybrid ◽  
Fischer 344 ◽  
Lv Mass

The effects of aging on cardiovascular function and cardiac structure were determined in a rat model recommended for gerontological studies. A cross-sectional analysis assessed cardiac changes in male Fischer 344 × Brown Norway F1 hybrid rats (FBN) from adulthood to the very aged ( n = 6 per 12-, 18-, 21-, 24-, 27-, 30-, 33-, 36-, and 39-mo-old group). Rats underwent echocardiographic and hemodynamic analyses to determine standard values for left ventricular (LV) mass, LV wall thickness, LV chamber diameter, heart rate, LV fractional shortening, mitral inflow velocity, LV relaxation time, and aortic/LV pressures. Histological analyses were used to assess LV fibrotic infiltration and cardiomyocyte volume density over time. Aged rats had an increased LV mass-to-body weight ratio and deteriorated systolic function. LV systolic pressure declined with age. Histological analysis demonstrated a gradual increase in fibrosis and a decrease in cardiomyocyte volume density with age. We conclude that, although significant physiological and morphological changes occurred in heart function and structure between 12 and 39 mo of age, these changes did not likely contribute to mortality. We report reference values for cardiac function and structure in adult FBN male rats through very old age at 3-mo intervals.

Dichlorvosand Mononuclear Cell Leukemia in Fischer 344 Rats: Lack of Effect of Chronic Administration on Progression of the Disease

1997 ◽  
Vol 16 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Ann Manley ◽  
W. Ray Brown ◽  
John Mennear
Keyword(s):  
Mononuclear Cell ◽  
Technology Policy ◽  
Corn Oil ◽  
Chronic Administration ◽  
Male Rats ◽  
Fischer 344 Rats ◽  
Cell Leukemia ◽  
Carcinogenic Effect ◽  
Fischer 344 ◽  
National Toxicology Program

The National Toxicology Program reported that the daily administration of dichlorvos, in the form of a corn oil gay age, was associated with an increased incidence of mononuclear cell leukemia (MCL) in male but not female Fischer 344 rats. Because of the high degree of variability with which this neoplasm appears in groups of control laboratory rats, supportive evidence is frequently sought to facilitate interpretation of increased incidences of the disease in chronic toxicity and carcinogenesis studies. In the National Toxicology Program study MCL was increased in only one sex of rats (m ales), did not occur earlier in DDVP-dosed than in control animals, and there was no evidence of a dose-response relationship. The U.S. Office of Science Technology Policy has recommended that the presence or absence of treatment-associated changes in tumor progression be employed as an adjunct in the interpretation of common tumors in rodents. The present study employed evaluative criteria described by the National Toxicology Program to determine the effects of DDVP on the progression of MCL in affected male rats. The results revealed that DDVP had no effect on either the severity or progression of MCL in male rats. Since there is no corroborative evidence supporting the interpretation of the increased incidence of MCL in male rats, this isolated DDVP-associated finding in a single sex of rats should not be considered to be evidence of a carcinogenic effect.

scholarly journals Allicin Reversed the Process of Frailty in Aging Male Fischer 344 Rats With Osteoporosis

2019 ◽  
Vol 75 (5) ◽  
pp. 821-825 ◽  
Author(s):  
Yang Liu ◽  
Meigui You ◽  
Jianwei Shen ◽  
Yaping Xu ◽  
Lin Li ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Frailty Index ◽  
Male Rats ◽  
Bending Test ◽  
Fischer 344 Rats ◽  
Aging Male ◽  
Mineral Density ◽  
Fischer 344

Abstract The research and development of pharmaceutical intervention is insufficient for the frail older adults, especially in preclinical stage for the frail individuals with osteoporosis. Garlic exerts an antiosteoporotic effect and its vital component allicin could protect organisms against aging. The present study aimed to investigate the effect of long-term intragastric administration of allicin (low dose of 4 mg·kg−1·d−1; middle dose of 8 mg·kg−1·d−1; high dose of 16 mg·kg−1·d−1) on frailty with osteoporosis in aging male Fischer 344 rats. Frailty was assessed with a 27-item frailty index based on quantifying health-related deficits in adult male rats varied from 13 to 21 months and in control rats from 6 to 9 months. Osteoporosis was appraised by bone mineral density detected by dual-energy X-ray absorptiometry, biomechanical properties measured by a three-point bending test, and bone metabolic analysis using ELISA. Allicin could attenuate frailty index scores by reducing the accumulation of health deficits in aging male Fischer 344 rats. Meanwhile, allicin could protect against senile osteoporosis, and the underlying mechanism may involve in increasing low bone turnover through elevation of both bone formation and bone resorption, and subsequently lead to increase of bone mineral density, contributing to reversing deleterious bone biomechanical features associated with aging. The present study reveals firstly that long-term oral administration with allicin attenuated frailty with osteoporosis during the process of aging, which provides a preclinical evidence for intervention of frailty.

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