Alterations in alpha1-adrenoceptor stimulation of isolated atria from experimental diabetic rats

1986 ◽  
Vol 64 (2) ◽  
pp. 145-151 ◽  
Author(s):  
Charles V. Jackson ◽  
Gail M. McGrath ◽  
John H. McNeill
Keyword(s):  
Experimental Diabetes ◽  
Receptor Activation ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Beta Adrenoceptor ◽  
Chemically Induced ◽  
Isolated Atria ◽  
And Control ◽  
Right Atria ◽  
Stimulation Of

This purpose of this investigation was to determine the influence of experimental diabetes (3 months) on the responsiveness of rat isolated atria to alpha1-adrenoceptor stimulation by phenylephrine. Diabetes was chemically induced with streptozotocin (65 mg/kg i.v.) in 42- to 43-day-old, nonfasted male Sprague–Dawley derived rats. Chronotropic (right atria) and inotropic (left atria) indices were recorded in response to alpha1-adrenoceptor stimulation by phenylephrine. These experiments were performed in the presence of beta-adrenoceptor antagonism (timolol). Isolated right atria from diabetic rats demonstrated a greater increase in heart rate in response to phenylephrine than did corresponding control atria. Left atria were supersensitive (decrease in EC50 values) and hyperresponsive to alpha1-adrenoceptor stimulation by phenylephrine when compared with stimulation of control left atria. Diabetic left atria in response to phenylephrine were observed to exchange more radioactive calcium (45Ca2+) than control left atria, whereas both diabetic and control left atria exchanged the same amount of 45Ca2+ during basal contractile conditions. Phenylephrine had no effect on 45Ca2+ efflux from either diabetic or control atria. These results indicate that 3 months of uncontrolled experimental diabetes in the rat produces an enhancement of alpha1-adrenoceptor activation of isolated atria, and that there is an alteration in Ca2+ mobilization which may contribute to the enhanced receptor activation.

Nitric oxide and penile erection in streptozotocin-diabetic rats

1999 ◽  
Vol 96 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Gil ARI ◽  
Yoram VARDI ◽  
John P. M. FINBERG
Keyword(s):  
Methyl Ester ◽  
Time Course ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
No Synthase ◽  
Sprague Dawley ◽  
Nerve Roots ◽  
Sprague Dawley Rats ◽  
Pithed Rats ◽  
Stimulation Of

The purpose of this investigation was to study the time course, response to insulin and characteristics of erectile dysfunction in streptozotocin (STZ)-diabetic Sprague–Dawley rats, and the function of the NO-generating system in these animals. Copulation-induced and reflex erection were quantified in conscious Sprague–Dawley rats at different times after injection of STZ. The corporal vasodilatation response to nerve stimulation was studied by measuring the rise in corporal pressure in pithed rats following electrical stimulation of sacral spinal nerve roots. The activity of NO synthase was determined in corporal tissue by measuring the generation of [3H]citrulline from [3H]arginine. Copulation-induced erection was inhibited at 1 and 2 months after STZ treatment, but this could be prevented by a short (2-week) pretreatment with insulin. Reflex erection was inhibited at 1, 4, 6 and 9 months after STZ; at 6 months, this inhibition was also reversible by insulin pretreatment. Following pithing, the basal corporal pressure was elevated in diabetic rats. At 4 months after STZ, this increase was normalized by a 2-week, but not by a 1-week, pretreatment with insulin; however, at 9 months after STZ, insulin pretreatment did not normalize corporal pressure. The increase in corporal pressure caused by stimulation of sacral nerve roots in pithed rats was enhanced in diabetic animals. This enhancement was also normalized at 4 months, but not at 9 months, by 2 weeks of insulin treatment. The inhibition of the stimulation-induced increase in corporal pressure by NG-nitro-L-arginine methyl ester (5 mg/kg) was less following 9 months of diabetes, although NO synthase activity was normal in cavernosal tissue following 6–8 months of diabetes. In conclusion, STZ-induced diabetes caused changes in the erectile system that were initially reversible by a short insulin treatment, but which with time (more than 6 months) became irreversible. NO synthase activity in cavernosal tissue was normal, but the response to NG-nitro-L-arginine methyl ester was inhibited in long-term diabetes (9 months).

Sympathetic and parasympathetic component of bradycardia triggered by stimulation of NTS P2X receptors

2006 ◽  
Vol 290 (2) ◽  
pp. H807-H812 ◽  
Author(s):  
Amy M. Kitchen ◽  
Donal S. O'Leary ◽  
Tadeusz J. Scislo
Keyword(s):  
Low Dose ◽  
Nucleus Tractus Solitarius ◽  
Receptor Activation ◽  
P2x Receptors ◽  
P2x Receptor ◽  
High Dose ◽  
Adrenergic Blockade ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Stimulation Of

We have previously shown that activation of P2X purinoceptors in the subpostremal nucleus tractus solitarius (NTS) produces a rapid bradycardia and hypotension. This bradycardia could occur via sympathetic withdrawal, parasympathetic activation, or a combination of both mechanisms. Thus we investigated the relative roles of parasympathetic activation and sympathetic withdrawal in mediating this bradycardia in chloralose-urethane anesthetized male Sprague-Dawley rats. Microinjections of the selective P2X purinoceptor agonist α,β-methylene ATP (25 pmol/50 nl and 100 pmol/50 nl) were made into the subpostremal NTS in control animals, after atenolol (2 mg/kg iv), a β1-selective antagonist, and after atropine methyl bromide (2 mg/kg iv), a muscarinic receptor antagonist. The bradycardia observed with activation of P2X receptors at the low dose of the agonist is mediated almost entirely by sympathetic withdrawal. After β1-adrenergic blockade, the bradycardia was reduced to just −5.1 ± 0.5 versus −28.8 ± 5.1 beats/min in intact animals. Muscarinic blockade did not produce any significant change in the bradycardic response at the low dose. At the high dose, both β1-adrenergic blockade and muscarinic blockade attenuated the bradycardia similarly, −37.4 ± 6.4 and −40.6 ± 3.7 beats/min, respectively, compared with −88.0 ± 11 beats/min in control animals. Double blockade of both β1-adrenergic and muscarinic receptors virtually abolished the response (−2.5 ± 0.8 beats/min). We conclude that the relative contributions of parasympathetic activation and sympathetic withdrawal are dependent on the extent of P2X receptor activation.

Dopamine DA1 receptor agonist, fenoldopam, reverses glycine-induced hyperfiltration in rats

1992 ◽  
Vol 262 (6) ◽  
pp. F1055-F1060 ◽  
Author(s):  
Y. X. Wang ◽  
M. Gellai ◽  
D. P. Brooks
Keyword(s):  
Glomerular Filtration Rate ◽  
Receptor Agonist ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Sch 23390 ◽  
Receptor Activation ◽  
Diabetic Rats ◽  
Glomerular Hyperfiltration ◽  
Filtration Fraction ◽  
Stimulation Of

Stimulation of dopamine DA1 receptors can prevent glomerular hyperfiltration in streptozotocin-induced diabetic rats. In the present study we have therefore investigated whether the DA1 agonist, fenoldopam, can prevent glycine-induced hyperfiltration. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and p-aminohippurate clearances in conscious chronically instrumented rats. Glycine (3.7 mg/min iv; n = 8) significantly increased GFR by 37% (from 1.09 +/- 0.53 to 1.49 +/- 0.11 ml.100 g-1.min-1, P less than 0.01), ERPF by 23% (from 2.96 +/- 0.30 to 3.64 +/- 0.43 ml.100 g-1.min-1, P less than 0.05), and filtration fraction (FF) by 13% (from 0.39 +/- 0.04 to 0.44 +/- 0.05, P less than 0.05). Fenoldopam, at a dose (1 microgram.kg-1.min-1 iv; n = 8) that increased ERPF by 26%, decreased FF by 13%, but did not change GFR, significantly attenuated the glycine-induced hyperfiltration. In the presence of fenoldopam, glycine resulted in only an 8% increase in GFR (from 1.08 +/- 0.07 to 1.17 +/- 0.09 ml.100 g-1.min-1; n = 8). ERPF increased by 20% (from 3.34 +/- 0.24 to 4.00 +/- 0.21 ml.100 g-1.min-1, P less than 0.05), and FF decreased by 13% (from 0.34 +/- 0.03 to 0.29 +/- 0.02, P less than 0.05). Infusion of the DA1-selective antagonist, Sch 23390, abolished the effects of fenoldopam. Thus DA1 receptor activation can prevent glomerular hyperfiltration induced by glycine.

Effect of caloric restriction on cardiac reactivity and beta-adrenoceptor concentration

1983 ◽  
Vol 244 (3) ◽  
pp. H444-H448 ◽  
Author(s):  
D. L. Crandall ◽  
F. M. Lai ◽  
F. J. Huggins ◽  
T. K. Tanikella ◽  
P. Cervoni
Keyword(s):  
Body Weight ◽  
Caloric Restriction ◽  
Body Fat ◽  
Heart Weight ◽  
Sprague Dawley ◽  
Fat Pad ◽  
Dietary Regimen ◽  
Beta Adrenoceptor ◽  
Cardiac Reactivity ◽  
Isolated Atria

The effect of a 21-day program of caloric restriction on cardiac reactivity and beta-adrenoceptor number was investigated in male Sprague-Dawley rats. Rats on the restricted diet (Restricted) exhibited significant decreases in body weight, epididymal fat pad, and retroperitoneal fat pad weight as well as the percent of body fat represented by these adipose tissue depots when compared with rats fed ad libitum (Fed). Fed rats exhibited significantly increased total heart weight and total heart protein, but the percent cardiac protein and ratio of heart weight to body weight were similar in Fed and Restricted rats. Isolated atria from Fed and Restricted rats developed similar chronotropic and inotropic responses over a range of isoproterenol concentrations. Although total beta-adrenoceptor number (fmol/heart) was greater in Fed rats, the concentration of beta-adrenoceptors (fmol/mg protein) was remarkably similar regardless of the dietary regimen. Therefore, despite significant decreases in body weight, body fat, and heart weight, the myocardium of Restricted rats maintained the capability of responding to isoproterenol as that of Fed rats, the mechanism of which is at least partially mediated through maintenance of beta-adrenoceptor concentration.

scholarly journals Diabetes with and without ketoacidosis on right atrial pacemaker rate and autonomic responsiveness

1997 ◽  
Vol 273 (4) ◽  
pp. H1888-H1893 ◽  
Author(s):  
Kristine K. Hicks ◽  
Ernst Seifen ◽  
Joseph R. Stimers ◽  
Richard H. Kennedy
Keyword(s):  
Insulin Dependent Diabetes Mellitus ◽  
Cholinergic Receptor ◽  
Receptor Activation ◽  
Diabetic Rats ◽  
Right Atrial ◽  
Dependent Diabetes Mellitus ◽  
Half Maximal Effective Concentration ◽  
Insulin Dependent ◽  
Chronotropic Action ◽  
Right Atria

Experiments were designed to determine whether insulin-dependent diabetes mellitus (IDDM) alters direct chronotropic effects of adrenergic and cholinergic agonists and whether the observed changes are associated with hyperglycemia or combined hyperglycemia and ketoacidosis. Diabetes was induced by intravenous administration of 45, 50, or 65 mg/kg streptozotocin (STZ). Rats treated with 65 mg/kg STZ had higher levels of blood glucose and ketones compared with the levels of the other groups. Right atria were isolated 12 wk after administration of STZ and bathed in Krebs-Henseleit solution. Basal spontaneous pacemaker rate was diminished in preparations isolated from diabetic rats. The maximum pacemaker rate observed during exposure to isoproterenol or norepinephrine was also depressed in preparations from diabetic animals; however, the increase in rate and half-maximal effective concentration values for each agent were not affected. The sensitivity to the negative chronotropic action of acetylcholine was enhanced by IDDM, whereas the response to carbachol (a cholinergic agonist not readily metabolized by acetylcholinesterase) was not changed. No significant differences were observed when we compared preparations isolated from diabetic animals with and without ketoacidosis. In summary, these data suggest 1) that IDDM is associated with a diminished basal spontaneous pacemaker without changes in the responsiveness to adrenergic and cholinergic receptor activation and 2) that ketoacidosis does not play a role in the observed alterations.

Mitochondrial dysfunction accompanies diastolic dysfunction in diabetic rat heart

1996 ◽  
Vol 271 (1) ◽  
pp. H192-H202 ◽  
Author(s):  
C. E. Flarsheim ◽  
I. L. Grupp ◽  
M. A. Matlib
Keyword(s):  
Atp Synthesis ◽  
Insulin Dependent Diabetes Mellitus ◽  
Work Load ◽  
Diabetic Rats ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Rat ◽  
Synthesis Rate ◽  
Insulin Dependent ◽  
And Control ◽  
Stimulation Of

The objective of this study was to determine whether a defect in mitochondrial respiratory function accompanies the development of diabetic cardiomyopathy. The hypothesis tested in this study is that a decrease in Ca2+ uptake into mitochondria may prevent the stimulation of Ca(2+)-sensitive matrix dehydrogenases and the rate of ATP synthesis. Streptozotocin (55 mg/kg)-induced diabetic rats were used as a model of insulin-dependent diabetes mellitus. Hearts from 4-wk diabetic rats had basal heart rates and rates of contraction and relaxation similar to control. Isoproterenol caused a similar increase in the rate of contraction in diabetic and control hearts, whereas the peak rate of relaxation was reduced in diabetic hearts. Mitochondrial Ca2+ uptake was reduced in mitochondria from diabetic hearts after 2 wk of diabetes. Na(+)-induced Ca2+ release was unchanged. State 3 respiration rate was depressed in mitochondria from diabetic rats only when the respiration was supported by the substrate of a Ca(2+)-regulated matrix enzyme. The pyruvate dehydrogenase activity was reduced in diabetic mitochondria compared with that of control. It was concluded that mitochondria from diabetic hearts had a decreased capacity to upregulate ATP synthesis via stimulation of Ca(2+)-sensitive matrix dehydrogenases. The impairment in the augmentation of ATP synthesis rate accompanies a decreased rate of relaxation during increased work load.

scholarly journals Expression of autophagy and apoptosis-related factors in the periodontal tissue of experimental diabetic rats: a histomorphometric, microtomographic and immunohistochemical study

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11577
Author(s):  
Youmin Mei ◽  
Xiang Shen ◽  
Xiaoqian Wang ◽  
Min Zhang ◽  
Qiao Li ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
B Cell Lymphoma ◽  
Diabetic Rats ◽  
Control Group ◽  
Periodontal Tissue ◽  
Sprague Dawley ◽  
Related Factors ◽  
Diabetes Group ◽  
Citrate Buffer ◽  
And Control

Objective This study aimed to investigate the expression of autophagy-related factors microtubule-associated protein l light chain 3 (LC3) and the apoptosis-related factors BCL2-associated X protein (Bax) and B cell lymphoma-2 (Bcl-2) in the periodontal tissue of experimental diabetic rats. These data were used to explore the potential mechanism in diabetes-induced periodontal tissue lesions. Methods A total of 32 Sprague Dawley (SD) rats were randomly assigned into diabetes (group D, n = 16) and control groups (group N, n = 16). The diabetic group was induced by intraperitoneal injection of 1% streptozotocin (STZ, 60 mg/kg) and the control group was injected with citrate buffer (0.1mol/L). Rats were sacrificed after 4 and 8 weeks of feeding and collected as D1, N1 groups and D2, N2 groups, and the maxilla were retained for analysis. The changes in periodontal tissue structure were observed by hematoxylin-eosin (HE) staining. The expression and distribution of LC3, Bax and Bcl-2 in the periodontium of the rats was detected by immunohistochemical (SP) staining. Results Diabetic rats showed several changes compared to control animals including sparse alveolar bone trabecular structure, loss of the lamina dura and absorption of the local alveolar bone. The positive expression level of LC3 in the gingival epithelial, periodontal ligament and alveolar bone of group D1 was significantly higher than in the N1, N2 and D2 groups (P < 0.05). The level of Bax expression in the group D2 rats was significantly higher than those in the N1, N2 and D1 groups (P < 0.05), while the positive degree of Bcl-2 was significantly lower than those of other groups (P < 0.001). LC3 was negatively correlated with Bax and was irrelevant with Bcl-2; Bcl-2 was not correlated with Bax. Conclusions The expression of LC3, Bax and Bcl-2 changes in the periodontal tissue of diabetic rats may indicate that autophagy and apoptotic are involved in the process of periodontal tissue damage in diabetic rats. These changes may be one of the mechanisms of periodontal tissue lesions.

Enalapril (E) Attenuates Oxidative Stress (OXS) in Diabetic Rats.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 726-726
Author(s):  
Elena MV de Cavanagh ◽  
Cesar G Fraga ◽  
Jorge E Toblli ◽  
Felipe Inserra ◽  
Leon F Ferder
Keyword(s):  
Oxidative Stress ◽  
Drinking Water ◽  
Cardiac Tissue ◽  
Tissue Injury ◽  
Tap Water ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Total Glutathione ◽  
Tubulointerstitial Lesions ◽  
And Control

P183 Oxidative stress has been involved as a possible mechanism of tissue injury. The effect of E on OxS and tissue injury was studied in kidney and heart from streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley, were divided into: STZ (65 mg/kg, single i.p. dose); STZ+E (STZ and E, 20 mg E /L drinking water), and Control (C) (saline i.p. and tap water). At 6 mo. organs were studied by light microscopy. Glomerular (GML) and tubulointerstitial lesions (TIL) were graded by a semiquantitative score (0-4). Glycemia, creatinine clearance (CrCl) and proteinuria were determined. OxS was evaluated by determining total glutathione content (GSH), protein-associated sulfhydryls (SH) and 2-thiobarbituric reactive substances (TBARS, an indicator of lipid oxidation) in kidney and heart homogenates. In STZ rats E decreased proteinuria, GML and TIL,and increased CrCl. In kidney and heart, E attenuated OxS associated to STZ. Results suggest that, in addition to previously described mechanisms, E might protect renal and cardiac tissue by attenuating OxS in STZ-induced diabetic rats.

Soluble and particulate phenylethanolamine N-methyltransferase in hypothalamus of diabetic rats

1992 ◽  
Vol 263 (2) ◽  
pp. E335-E339
Author(s):  
J. E. Chappell ◽  
J. K. Stewart
Keyword(s):  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Particulate Fraction ◽  
Sprague Dawley ◽  
Rat Hypothalamus ◽  
Tissue Extracts ◽  
Sprague Dawley Rats ◽  
In Vitro Response

Experimental diabetes increases total phenylethanolamine N-methyltransferase (PNMT) activity in the medulla-pons but not in the hypothalamus. In this study diabetes was induced with streptozotocin (65 mg/kg) in male Sprague-Dawley rats. Twenty-eight days after treatment there were no differences in soluble PNMT activity in the hypothalamus of diabetics and controls, but PNMT activity in a membrane-associated (particulate) fraction of hypothalamus was evaluated approximately twofold in tissues of diabetic animals compared with controls. A specific PNMT inhibitor, incubated with tissue extracts of control rats, abolished greater than 90% of particulate PNMT activity in the hypothalamus but reduced soluble PNMT activity in the hypothalamus by only 47%. These findings indicate that membrane-associated PNMT activity in rat hypothalamus differs from soluble hypothalamic PNMT in the in vitro response to an inhibitor and the in vivo response to diabetes and suggest the importance of separating subcellular hypothalamic fractions prior to assay of PNMT.

Platelet Abnormalities in Experimental Diabetes

1979 ◽  
Author(s):  
M. Johnson ◽  
H.E. Harrison ◽  
R. Hawker ◽  
L. Hawker
Keyword(s):  
Platelet Function ◽  
Experimental Diabetes ◽  
Platelet Reactivity ◽  
Vascular Complications ◽  
Diabetic Rats ◽  
Thromboxane Synthetase ◽  
Patients With Diabetes ◽  
Streptozotocin Diabetic Rats ◽  
And Control

Many abnormalities of platelet function occur in patients with diabetes mellitus, partioularly those with angiopathy. We have previously demonstrated that prostacyclin (PGI2) is decreased in streptozotocin-diabetic rats, and have now investigated platelet reactivity in these animals. Responsiveness to ADP and arachidonlc acid was increased, and platelet cyclo-oxygenase and thromboxane synthetase activities were significantly elevated (p<0.05) in diabetic animals (5.5±0.7 and 5.9±0.9 arbitrary units/109 platelets) when compared with control animals (J.0±0.4 and 3.9±0.3 arbitrary units/109 platelets). Malondialdehyde synthesis was 1,5 and 0.9 n moles per 108 platelets in diabetic and control rats respectively. Diabetic platelets were also less sensitive to the anti-aggregating effects of PGI2 (IC50: diabetic, 2.3 ng/ml; control, 1.3 ng/ml. Survival of illindium-labelled autologous platelets was significantly reduced, indicating that platelet function is abnormal in vivo, in diabetic animals. Platelet hyper-reactivity, possibly associated with depressed PGI2, could be related to the vascular complications of diabetes.

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