β-Adrenergic responsiveness of rats treated chronically with isoproterenol

1980 ◽  
Vol 58 (10) ◽  
pp. 1170-1173 ◽  
Author(s):  
C. C. Barney ◽  
M. J. Katovich ◽  
M. J. Fregly ◽  
P. E. Tyler

The effect of chronic administration of isoproterenol on isoproterenol-induced thirst and isoproterenol-induced changes in heart rate and selected organ weights of male rats was studied. Administration of 25 μg isoproterenol/kg, s.c., in saline daily for 10 days was accompanied by a significant attenuation of the characteristic increase in water intake following a challenging dose of isoproterenol (25 μg/kg, s.c.) on the 11th day. Administration of 25 μg isoproterenol/kg, s.c., every 2nd, 3rd, or 4th day for 10 days was without significant effect on water intake following isoproterenol (25 μg/kg, s.c.) on the 11th day. Administration of 25 μg isoproterenol/kg, s.c., every day for 10 days led to a slight increase in cardiac responsiveness to a challenging dose of isoproterenol (25 μg/kg) on the 11th day. Chronic treatment with this low dose of isoproterenol for 10 days was also accompanied by a significant increase in the ratio of heart weight to body weight but no significant changes in the ratio of kidney, adrenal, thyroid, spleen, or interscapular brown fat to body weight. Thus, daily administration of the β-adrenergic agonist isoproterenol for 10 days can alter β-adrenergic responsiveness in the rat with β1 (heart rate) and β2 (thirst) mediated responses showing opposite effects. In addition, the results suggest that tests of β-adrenergic responsiveness must be assessed in terms of the frequency of administration of the agonist.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Thomas Dieterle ◽  
Silvia Meili-Butz ◽  
Katrin Buehler ◽  
Christian Morandi ◽  
Dietlinde John ◽  
...  

Background: Recently, novel corticotropin-releasing factor (CRF)-related peptides, named urocortin I (UcnI), UcnII, and UcnIII were described. Available data suggest that the Ucns are part of a peripheral CRF system modulating cardiovascular function and mediating cardiovascular responses to stress. Blood pressure (BP) lowering effects have been described after administration of UcnI. However, no data are available on effects of UcnII on BP in an animal model of systemic arterial hypertension. Methods: Experiments were performed in Dahl salt-sensitive (DSS) and salt-resistant rats (DSR, control). Animals were fed a diet containing 4% NaCl (high salt) to induce arterial hypertension in DSS rats. At the end of week 2 of high salt diet, both DSS and DSR rats were randomly assigned to i.p. injections of either UcnII (2.5 μg/kg body weight) or vehicle b.i.d. for five weeks. Animals underwent repetitive tail cuff BP measurements at baseline (prior to first injection), at 5 and 15 minutes after the first injection and at week 1, 2, and 5 of b.i.d. treatment. At week 5 animals were sacrificed to determine heart weight /body weight ratio. Results: Systolic BP (SBP, mmHg) and heart rate (HR, min −1 ) are given in the following table as mean ± SD (n=10 per group). Conclusions: In hypertensive DSS rats, acute CRF-receptor stimulation by UcnII immediately lowered BP to the range observed in DSR rats. Compared to vehicle-treated DSS rats, sustained BP reduction was observed with further chronic administration of UcnII. No severe reflex tachycardia was observed after administration of UcnII. Thus, CRF-receptor stimulation might represent a novel approach to the treatment of arterial hypertension.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Soheb Anwar Mohammed ◽  
Bugga Paramesha ◽  
Yashwant Kumar ◽  
Ubaid Tariq ◽  
Sudheer Kumar Arava ◽  
...  

Allylmethylsulfide (AMS) is a novel sulfur metabolite found in the garlic-fed serum of humans and animals. In the present study, we have observed that AMS is safe on chronic administration and has a potential antihypertrophic effect. Chronic administration of AMS for 30 days did not cause any significant differences in the body weight, electrocardiogram, food intake, serum biochemical parameters, and histopathology of vital organs. Single-dose pharmacokinetics of AMS suggests that AMS is rapidly metabolized into Allylmethylsulfoxide (AMSO) and Allylmethylsulfone (AMSO2). To evaluate the efficacy of AMS, cardiac hypertrophy was induced by subcutaneous implantation of ALZET® osmotic minipump containing isoproterenol (~5 mg/kg/day), cotreated with AMS (25 and 50 mg/kg/day) and enalapril (10 mg/kg/day) for 2 weeks. AMS and enalapril significantly reduced cardiac hypertrophy as studied by the heart weight to body weight ratio and mRNA expression of fetal genes (ANP and β-MHC). We have observed that TBARS, a parameter of lipid peroxidation, was reduced and the antioxidant enzymes (glutathione, catalase, and superoxide dismutase) were improved in the AMS and enalapril-cotreated hypertrophic hearts. The extracellular matrix (ECM) components such as matrix metalloproteinases (MMP2 and MMP9) were significantly upregulated in the diseased hearts; however, with the AMS and enalapril, it was preserved. Similarly, caspases 3, 7, and 9 were upregulated in hypertrophic hearts, and with the AMS and enalapril treatment, they were reduced. Further to corroborate this finding with in vitro data, we have checked the nuclear expression of caspase 3/7 in the H9c2 cells treated with isoproterenol and observed that AMS cotreatment reduced it significantly. Histopathological investigation of myocardium suggests AMS and enalapril treatment reduced fibrosis in hypertrophied hearts. Based on our experimental results, we conclude that AMS, an active metabolite of garlic, could reduce isoproterenol-induced cardiac hypertrophy by reducing oxidative stress, apoptosis, and stabilizing ECM components.


1987 ◽  
Vol 252 (4) ◽  
pp. H788-H795 ◽  
Author(s):  
K. H. McDonough ◽  
V. Chen ◽  
J. J. Spitzer

Effect of a chronic excess or deficit of thyroid hormone on intrinsic myocardial performance in rats was assessed. Animals were thyroidectomized or treated with thyroid hormone or vehicle 6-7 wk before the study. Body weight and heart weight were decreased in the hypothyroid group, and heart weight was elevated in the hyperthyroid group. Hearts were removed from thyroidectomized, euthyroid or thyroid-treated animals and studied as isolated, perfused working heart preparations. Ventricular function curves were generated by increasing left atrial filling pressure, whereas outflow resistance was not varied. Coronary flow, aortic outflow (and thus cardiac output), heart rate, and peak aortic systolic pressure were measured as a function of preload. These studies showed that performance of hearts from hyperthyroid animals was similar to that of euthyroid controls. Hearts from hypothyroid rats had decreased rate, pressure, and cardiac output but normal stroke volume. Since heart weight was 55% lower than control, normalization of volume work to dry heart weight reversed the difference in cardiac output. Comparison of hearts from hypothyroid animals to control rats of similar weight showed minimal differences in pump function. Thus hyperthyroidism did not result in altered in vitro cardiac output or peak systolic pressure as a function of changing preload when compared with age-matched euthyroid controls, hypothyroidism resulted in a decreased in vitro heart rate but greater cardiac output normalized to heart weight when compared with age-matched controls and hyperthyroid animals; external pacing of hypothyroid hearts yielded myocardial work parameters that were comparable to euthyroid control rats of similar body weight; and cardiac efficiency was significantly greater in hypothyroid hearts than in hyperthyroid hearts.(ABSTRACT TRUNCATED AT 250 WORDS)


1959 ◽  
Vol 196 (3) ◽  
pp. 520-524 ◽  
Author(s):  
Henry B. Hale ◽  
Roy B. Mefferd ◽  
Gordon Vawter ◽  
G. Elizabeth Foerster ◽  
Dominic Criscuolo

A comparison was made of the morphological effects of cold, heat and simulated altitude on adult male rats given exposures of 24 weeks' duration. By the use of covariance analysis it was possible to determine the extent to which organ weights were dependent upon body weight and to adjust the values in order to remove body weight influences. For liver, heart and kidney, adjusted weights indicated temperature-dependency, while pressure-dependency was established for liver and kidney only. Histologically, temperature-dependency was indicated for liver, kidney, thyroid, adrenal and pituitary. Fur weight was reduced in heat but not altered in cold. Fasting in cold induced changes in adrenal and thymus weight and unusually high body weight loss; in heat, fasting caused a significant thymus weight loss without adrenal weight increase. The thymus-adrenal ratio was elevated during a 24-hour fast in all environments except cold, where it was decreased.


Biologia ◽  
2006 ◽  
Vol 61 (3) ◽  
Author(s):  
Monika Kassayová ◽  
Martina Marková ◽  
Bianka Bojková ◽  
Eva Adámeková ◽  
Peter Kubatka ◽  
...  

AbstractThe question of effects of long-term melatonin (MEL) administration have not yet been explained sufficiently, especially its metabolic consequences in young persons and animals. The aim of the present study was to analyze the effects of MEL given during prolonged time (for 3 months) and chronically (for 6 months) at the dose of 4 µg/mL of tap water, on the selected metabolic and hormonal parameters in young female and male Wistar:Han (WH) rats. The weights of selected organs, tissues, body weight gains and food and water intake were registered. Six weeks aged rats were adapted to standard housing conditions and light regimen L:D=12:12 h, fed standard laboratory diet and drank tap water (controls) or MEL solution ad libitum; finally they were sacrificed after overnight fasting. Prolonged MEL administration decreased serum glucose concentration and increased triacylglycerol and malondialdehyde concentration/content in the liver in females. In males MEL increased concentrations of serum phospholipids, corticosterone and liver malondialdehyde. MEL treatment reduced the body weight in both sexes and weight of epididymal fat in males, without any alterations of food and water intake. Chronic MEL administration reduced serum glucose concentration and increased concentration/content of glycogen, triacylglycerol and cholesterol in the liver and glycogen concentration/content in heart muscle in males. In females, the significant rise of serum corticosterone concentration and liver malondialdehyde content was recorded. MEL significantly increased liver weight and decreased thymus weight in males. MEL administration increased temporarily water intake in males, body and epididymal fat weights were similar to that in controls. Body weight of MEL drinking females was reduced in the 1st half of experiment only; the food and water intake did not differ from control group. The response in WH rats on MEL was more prominent as in the Sprague-Dawley strain (our previous studies). Male rats were generally more affected, probably due to higher daily and total consumption of melatonin.


2019 ◽  
Vol 3 (s1) ◽  
pp. 21-21
Author(s):  
Jonathas Fernandes Queiroz Almeida ◽  
Aline Souza ◽  
Hong Ji ◽  
Kathryn Sandberg

OBJECTIVES/SPECIFIC AIMS: The goal of this study was to determine if there are any sex differences in the pathophysiological effects of sFR. METHODS/STUDY POPULATION: Male Fischer rats (4-month-old) were maintained on a control (CT) (ad libitum regular chow; n=8) or sFR (60% reduction of daily food intake, n=8) diet for 2 weeks. On days 1, 2, 3 and 14, the rats were placed in metabolic cages for food and water intake and 24-hour urine collection. Body weight (BW) is measured daily. After 2 weeks, the animals are given free access to normal chow for 3 months. Short-term and long-term effects of sFR on blood pressure and heart rate will be measured. RESULTS/ANTICIPATED RESULTS: After 2 weeks, the male CT group gained 7% BW (p <0.05), while BW in the sFR males was reduced by 12% (p<0.05 vs. CT). In contrast, female controls did not gain BW while the sFR females lost 18% of their BW. Water intake was reduced by 35%, which was similar to the reduction in females (p=0.18). The hematocrit of sFR male rats was higher (51.1%) than the CT group (45.2%, p<0.05), which was most likely due to the 6% reduction in plasma volume. A similar effect on hematocrit was observed in sRF females. Similarly, also to female rats, sFR had no effect on Na+ and K+ plasma or urine concentrations by day 14 in the male rats. DISCUSSION/SIGNIFICANCE OF IMPACT: sFR has similar effects on electrolyte balance in males and females. Ongoing studies will determine if there is any sex difference in the effects of sFR on blood pressure, heart rate and susceptibility to hypertension and cardiac injury.


1976 ◽  
Vol 54 (3) ◽  
pp. 200-208 ◽  
Author(s):  
M. J. Fregly ◽  
G. E. Resch ◽  
E. L. Nelson Jr. ◽  
F. P. Field ◽  
P. E. Tyler

Chronic administration of aminotriazole (0.5 g/kg food) to rats was accompanied by a reduced responsiveness to acute administration of the β-adrenergic agonist, l-isoproterenol (50–100 μg/kg, sc). The responses tested included water intake, change in heart rate in the anesthetized and unanesthetized rat, change in mean blood pressure, and change in blood glucose concentration. In addition, the increase in tail skin temperature accompanying administration of epinephrine (1 mg/kg, sc) was significantly reduced in the hypothyroid group. Administration of l-thyroxine (25 μg/kg per day, ip) to aminotriazole-treated rats prevented the reduction in responsiveness to β-adrenergic stimulation. Thus, an interaction appears to exist between the level of thyroid activity and responsiveness to β-adrenergic agonists in rats.


1984 ◽  
Vol 105 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Masatomo Mori ◽  
Kihachi Ohshima ◽  
Hitoshi Fukuda ◽  
Isao Kobayashi ◽  
Katsumi Wakabayashi

Abstract. Heterogeneity of pituitary TSH was investigated in rats following thyroidectomy. Adult male rats were sacrificed at varying periods (2–28 days) after thyroidectomy. In another experiment, thyroidectomized rats were injected daily with various doses of l-T4 (0.3–7.5 μg/100 g body weight, ip) and sacrificed 2 weeks later. The homogenate of the pituitaries was applied on an isoelectric focusing column or a Sephacryl S-200 column. The normal rat pituitary contained 5 major components of immunoreactive (IR) TSH in isoelectric focusing, in which the isoelectric point (pi) ranged from 6.6 to 8.8. The multiple components of IR-TSGβ were observed almost in the same areas as those of IR-TSH. Following thyroidectomy IR-TSH components with more acidic pI, associated with IR-TSHβ, were evident. A large amount of IR-TSHβ in the pituitaries of thyroidectomized rats appeared near the void volume in gel filtration, suggesting the presence of big TSHβ Supplement of l-T4 minimized these thyroidectomy-induced changes in isoelectric focusing and gel filtration. Furthermore, big IR-TSHβ was little affected by ultracentrifugation and was relatively stable after treatment with 6 m guanidine hydrochloride. We demonstrated that the rat pituitary gland contained multiple components of IR-TSH and IR-TSHβ, both of which became variegated after thyroidectomy. It is suggested that a discernible degree of heterogeneity of TSH, particularly of TSHβ, is dependent upon the increased rate of TSH biosynthesis at the pituitary level.


2018 ◽  
Vol 69 (5) ◽  
pp. 1229-1232
Author(s):  
Eugeniu Mihalas ◽  
Adriana Balan ◽  
Ana Petcu (Sirghe) ◽  
Laura Gavrila ◽  
Carmen Savin

Amoxicillin it is the most commonly prescribed antibiotic agent and the first intention in the short-term treatment of infections in children. The aim of this study was to assess the effects of amoxicillin/clavulanic acid (AMC) chronic administration on the laboratory mice�s body weight (BW), water intake and values of non-fasting blood glucose levels (n-FBG). Thus, twenty-eight C57BL/6 male mice, of similar age, randomly divided into a control and 3 treatment groups (n = 7) received subcutaneous injection, once per day, for 60 days. During the experiment the n-FBG, daily water intake, and BW changes were recorded every 10 days. The results of our study revealed that the chronic administration of AMC, at a concentration of 100 and 150 mg/kg BW/day, increased capillary n-FGB, and can be associated with a significant increase in the BW and daily water intake in mice.


1965 ◽  
Vol 209 (6) ◽  
pp. 1089-1094 ◽  
Author(s):  
Charles M. Tipton

Bradycardia produced by training was investigated in 228 mature male rats belonging to normal, vagotomized, diencephalon-lesioned, immunological sympathectomized, and hypophysectomized groups. During a 70-day experimental period, resting heart rates of trained unanesthetized rats were significantly lower than those of non-trained rats at approximately 40 days after the training program had been initiated. Resting heart rates were correlated with body weight, wet and dry heart weight, percentage of solids, and the heart weight/body weight ratio (heart ratio). Several coefficients were statistically significant but the majority of the coefficients were below ±0.60 and exhibited a low relationship between the various parameters. Heart ratios for the trained vagotomized, diencephalon-lesioned, and immunological sympathectomized were significantly lower than the ratios from normal trained animals. Similar trends were observed with the nontrained subgroups when these ratios were compared with normal nontrained animals. The only exercising group that exhibited statistical evidence for cardiac hypertrophy was the normal trained group. It was concluded that other aspects beside the weight of the heart must be considered in any satisfactory explanation for this form of bradycardia.


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