Reduced renal dopamine D1 receptor function in streptozotocin-induced diabetic rats

2004 ◽  
Vol 286 (3) ◽  
pp. F451-F457 ◽  
Author(s):  
Aditi Marwaha ◽  
Anees Ahmad Banday ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Atpase Activity ◽  
Sodium Excretion ◽  
Type I Diabetes ◽  
Receptor Activation ◽  
Diabetic Rats ◽  
D1 Receptor ◽  
Skf 38393 ◽  
Receptor Expression ◽  
Type I ◽  
Renal Dopamine

Dopamine, via activation of renal D1 receptors, inhibits the activities of Na-K-ATPase and Na/H exchanger and subsequently increases sodium excretion. Decreased renal dopamine production and sodium excretion are associated with type I diabetes. However, it is not known whether the response to D1 receptor activation is altered in type I diabetes. The present study was designed to examine the effect of streptozotocin-induced type I diabetes on renal D1 receptor expression and function. Streptozotocin treatment of Sprague-Dawley rats caused a fourfold increase in plasma levels of glucose along with a significant decrease in insulin levels compared with control rats. Intravenous administration of SKF-38393, a D1 receptor agonist, caused a threefold increase in sodium excretion in control rats. However, SKF-38393 failed to produce natriuresis in diabetic rats. SKF-38393 caused a concentration-dependent inhibition of Na-K-ATPase activity in renal proximal tubules of control rats. However, the ability of SKF-38393 to inhibit Na-K-ATPase activity was markedly diminished in diabetic rats. D1 receptor numbers and protein abundance as determined by [3H]SCH-23390 ligand binding and Western blot analysis were markedly reduced in diabetic rats compared with control rats. Moreover, SKF-38393 failed to stimulate GTPγS binding in proximal tubular membranes from diabetic rats compared with control rats. We conclude that the natriuretic response to D1 receptor activation is reduced in type I diabetes as a result of a decrease in D1 receptor expression and defective receptor G protein coupling. These abnormalities may contribute to the sodium retention associated with type I diabetes.

Abstract 341: Synergistic Effects of Renal Dopamine and Gastrin Receptors in Hypertension

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Yue Chen ◽  
Shuo Zhen ◽  
Laureano Asico ◽  
Pedro Jose ◽  
Chunyu Zeng
Keyword(s):  
Atpase Activity ◽  
Sodium Excretion ◽  
Synergistic Effects ◽  
Inhibitory Effect ◽  
Receptor Interaction ◽  
Gastrin Receptor ◽  
Wky Rats ◽  
Link Type ◽  
Renal Dopamine ◽  
Stimulation Of

Oral NaCl produces stronger natriuresis and diuresis as compared with venous infusion of same amount of NaCl, indicating the existence of renal-gastric axis. Although numerous hormones are secreted in gastrointestinal tract, gastrin is evident one due to its natriuretic effects and taken-up by the renal proximal tubule (RPT) cells. We hypothesize that there is an interaction between gastrin and dopamine receptor in kidney, which synergistically increases sodium excretion, the impaired interaction would be involved in the pathogenesis of hypertension. In WKY rats, infusion of gastrin, via renal artery, induced natriuresis and diuresis, which was blocked in the presence of CI988, a gastrin receptor blocker. Similarly, the natriuretic and diuretic effect of fenoldopam, a D1-like receptor agonist, was blocked by the D1-like receptor antagonist, SCH23390 , indicating that gastrin and fenoldopam, via individual receptor, play natriuretic and diuretic effects. Our further study found that lower dosages of gastrin or fenoldopam could not induce natriuresis and diuresis alone, while putting together induced natriuretic and diuretic effects. The above-mentioned effects were lost in SHRs. We also found, in the presence of SCH23390 , gastrin-mediated natriuresis and diuresis was partially blocked. Similarly, in the presence of CI988, the natriuretic and diuretic effects of fenoldopam were partially blocked, indicating the interaction between gastrin and D1-like receptor. The gastrin/D1-like receptor interaction was also confirmed in the RPT cells. Stimulation of one receptor increased the expression of the other. Stimulation of either D1-like receptor or gastrin receptor inhibited the Na + -K + -ATPase activity in RPT cells, while in the presence of SCH23390 , the inhibitory effect of gastrin on Na + -K + -ATPase activity was partially blocked. In the presence of CI988, D1-like receptor-mediated inhibitory effect of Na + -K + -ATPase activity in RPT cells was partially inhibited. It indicated the synergistic effect between gastrin and D1-like receptor would increase the sodium excretion in WKY rats; the impaired interaction might be involved in the pathogenesis of hypertension.

scholarly journals Glycaemic control with insulin prevents the reduced renal dopamine D1 receptor expression and function in streptozotocin-induced diabetes

2010 ◽  
Vol 25 (9) ◽  
pp. 2945-2953 ◽  
Author(s):  
M. Moreira-Rodrigues ◽  
J. Quelhas-Santos ◽  
P. Serrao ◽  
C. Fernandes-Cerqueira ◽  
B. Sampaio-Maia ◽  
...  
Keyword(s):  
Glycaemic Control ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Receptor Expression ◽  
Streptozotocin Induced Diabetes ◽  
Renal Dopamine ◽  
And Function

scholarly journals In Utero Exposure to Fine Particulate Matter Causes Hypertension Due to Impaired Renal Dopamine D1 Receptor in Offspring

2018 ◽  
Vol 46 (1) ◽  
pp. 148-159 ◽  
Author(s):  
Zhengmeng Ye ◽  
Xi Lu ◽  
Yi Deng ◽  
Xinquan Wang ◽  
Shuo Zheng ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Particulate Matter ◽  
Sodium Excretion ◽  
Fine Particulate Matter ◽  
In Utero ◽  
D1 Receptor ◽  
In Utero Exposure ◽  
Fine Particulate ◽  
Pm2.5 Exposure ◽  
Renal Dopamine

Background/Aims: Adverse environment in utero can modulate adult phenotypes including blood pressure. Fine particulate matter (PM2.5) exposure in utero causes hypertension in the offspring, but the exact mechanisms are not clear. Renal dopamine D1 receptor (D1R), regulated by G protein-coupled receptor kinase type 4 (GRK4), plays an important role in the regulation of renal sodium transport and blood pressure. In this present study, we determined if renal D1R dysfunction is involved in PM2.5–induced hypertension in the offspring. Methods: Pregnant Sprague–Dawley rats were given an oropharyngeal drip of PM2.5 (1.0 mg/kg) at gestation day 8, 10, and 12. The blood pressure, 24-hour sodium excretion, and urine volume were measured in the offspring. The expression levels of GRK4 and D1R were determined by immunoblotting. The phosphorylation of D1R was investigated using immunoprecipitation. Plasma malondialdehyde and superoxide dismutase levels were also measured in the offspring. Results: As compared with saline-treated dams, offspring of PM2.5-treated dams had increased blood pressure, impaired sodium excretion, and reduced D1R-mediated natriuresis and diuresis, accompanied by decreased renal D1R expression and GRK4 expression. The impaired renal D1R function and increased GRK4 expression could be caused by increased reactive oxidative stress (ROS) induced by PM2.5 exposure. Administration of tempol, a redox-cycling nitroxide, for 4 weeks in the offspring of PM2.5-treated dam normalized the decreased renal D1R expression and increased renal D1R phosphorylation and GRK4 expression. Furthermore, tempol normalized the increased renal expression of c-Myc, a transcription factor that regulates GRK4 expression. Conclusions: In utero exposure to PM2.5 increases ROS and GRK4 expression, impairs D1R-mediated sodium excretion, and increases blood pressure in the offspring. These studies suggest that normalization of D1R function may be a target for the prevention and treatment of the hypertension in offspring of mothers exposed to PM2.5 during pregnancy.

An Evaluation of Different Methods of Peripheral Nerve Repair In Normal and Diabetic Rats

1997 ◽  
Vol 22 (4) ◽  
pp. 486-491 ◽  
Author(s):  
A. C. FULLARTON ◽  
M. A. GLASBY
Keyword(s):  
Nerve Regeneration ◽  
Nerve Injury ◽  
Type I Diabetes ◽  
Nerve Repair ◽  
Fibre Diameter ◽  
Diabetic Rats ◽  
Type I ◽  
Nerve Crush ◽  
Nerve Autograft ◽  
Type Of Injury

Successful nerve regeneration depends on the type of injury, the method of repair and the metabolic status of the animal. A state similar to poorly controlled Type I diabetes mellitus in man was induced and maintained in rats using streptozotocin. This provided a model for the study of nerve regeneration in diabetes over a period of 150 days. Two methods of nerve injury (crush and transection) and three methods of repair (epineurial suture, nerve autograft and freeze-thawed skeletal muscle autograft) were compared using electrophysiological and histological methods. The diabetic state did not affect the degree of recovery of nerve conduction velocity after nerve injury. By 150 days, recovery to control values of axon and nerve fibre diameters was not attained. Recovery of axon and fibre diameter was significantly poorer in the diabetic nerve crush group compared with the non-diabetic nerve crush group. It is concluded that this was because of poorer regeneration in diabetic nerve.

Defective renal dopamine function and sodium-sensitive hypertension in adult ovariectomized Wistar rats: role of the cytochromeP-450 pathway

2015 ◽  
Vol 308 (12) ◽  
pp. F1358-F1368 ◽  
Author(s):  
Luis A. Di Ciano ◽  
Pablo J. Azurmendi ◽  
Cecilia Colombero ◽  
Gloria Levin ◽  
Elisabet M. Oddo ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Wistar Rats ◽  
Sch 23390 ◽  
D1 Receptor ◽  
Phosphorylation State ◽  
High Sodium ◽  
Ovx Rats ◽  
Sodium Load ◽  
Renal Dopamine ◽  
Salt Sensitive Hypertension

We have previously shown that ovariectomy in adult Wistar rats under normal sodium (NS) intake results in an overexpression of the total Na+-K+-ATPase (NKA) α1-subunit (Di Ciano LA, Azurmendi PJ, Toledo JE, Oddo EM, Zotta E, Ochoa F, Arrizurieta EE, Ibarra FR. Clin Exp Hypertens 35: 475–483, 2013). Upon high sodium (HS) intake, ovariectomized (oVx) rats developed defective NKA phosphorylation, a decrease in sodium excretion, and an increment in mean blood pressure (MBP). Since NKA phosphorylation is modulated by dopamine (DA), the aim of this study was to compare the intracellular response of the renal DA system leading to NKA phosphorylation upon sodium challenge in intact female (IF) and oVx rats. In IF rats, HS caused an increase in urinary DA and sodium, in NKA phosphorylation state, in cytochrome P-4504A (CYP4A) expression, and in 20-HETE production, while MBP kept normal. Blockade of the D1 receptor (D1R) with the D1-like receptor antagonist SCH 23390 in IFHS rats shifted NKA into a more dephosphorylated state, decreased sodium excretion by 50%, and increased MBP. In oVxNS rats, D1R expression was reduced and D3R expression was increased, and under HS intake sodium excretion was lower and MBP higher than in IFHS rats (both P < 0.05), NKA was more dephosphorylated than in IFHS, and CYP4A expression or 20-HETE production did not change. Blockade of D1R in oVxHS rats changed neither NKA phosphorylation state nor sodium excretion or MBP. D2R and PKCα expression did not vary among groups. The alteration of the renal DA system produced by ovariectomy could account for the defective NKA phosphorylation, the inefficient excretion of sodium load, and the development of salt-sensitive hypertension.

The Protective Effects of Lupine (Lupinus albus) Fruit Extract Against to Destructive Effects of Hyperglycemia in Type I Diabetic Rats

2020 ◽  
Vol 20 ◽  
Author(s):  
Sevinç Aydın ◽  
Tubay Kaya ◽  
Orhan Erman ◽  
Ökkeş Yılmaz
Keyword(s):  
Lipid Peroxidation ◽  
Total Protein ◽  
Type I Diabetes ◽  
Lupinus Albus ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Type I ◽  
Protective Effects ◽  
Fruit Extract

Backround: Lupinus albus is a member of Fabaceae family. As a natural or cultivated plant, Lupinus albus is distributed in Europe, Balkans and Turkey, especially in Marmara and Aegean regions. The lupine is a nutritious and protective plant against diabetes. Objective: In the present study, the effects of Lupinus albus fruits on malondialdehyde (MDA), reduced glutathione (GSH), total protein, ADEK vitamins, and cholesterol values, which are the indicators of oxidative damage and antioxidant defense. In this regard, muscle, liver, renal, and brain tissues of STZ-induced type I diabetes rats were studied. Methods: The analyzes of ADEK vitamins and cholesterol levels in tissues were performed via Shimadzu HPLC device. The lipid peroxidation levels were measured at 532 nm in spectrophotometer. Determination of GSH was read at 412 nm against blank, and for the total protein levels Lowry method was applied. Results: According to the results obtained, it was determined that, among the rats with induced type I diabetes, the group applied lupine fruit extract was found to have increased GSH level and decreased MDA levels in all the tissues. The protein values were increased in liver tissues but decreased in the other tissues. The level of vitamins were significantly increased in almost all the tissues in diabetic group. Conclusion: In the present study, it was shown that the lupine reduced the devastating effects of type I diabetes by decreasing the fasting blood glucose and lipid peroxidation values and increasing the glutathione level in comparison to the diabetic group.

Abstract 281: Long-term Exposure of PM2.5 Causes Hypertension by Impaired Renal D1 Receptor Mediated Sodium Excretion via Up-regulation of GRK4 Expression in SD rats

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Xi Lu ◽  
Ken Chen ◽  
Jing Zeng ◽  
Hongmei Ren ◽  
Chunyu Zeng
Keyword(s):  
Sodium Excretion ◽  
D1 Receptor ◽  
Receptor Expression ◽  
Sd Rats ◽  
Induced Hypertension ◽  
Pm2.5 Exposure ◽  
And Function

Introduction: Epidemiological evidence supports an important association between PM2.5 exposure and hypertension. There are reports that PM2.5 induced hypertension with impaired sodium excretion, however, the mechanisms are not clear. Hypothesis: We hypothesize that PM2.5, via increased ROS levels, increased GRK4 expression, consequently impaired renal D1 receptor function, and lead to hypertension. Methods: We used Sprague-Dawley (SD) rats with in-vivo PM2.5 exposure, and immortalized renal proximal tubule (RPT) cells from Wistar-Kyoto (WKY) rats in-vitro, which behave similarly to freshly obtained RPT cells. Results: Our present study found that long-term exposure of PM2.5 caused hypertension and impaired renal sodium excretion, which might be ascribed to lower D1 receptor expression and higher D1 receptor phosphorylation, accompanied with higher GRK4 expression. The in-vivo results were confirmed in in-vitro study, i.e. PM2.5 increased basal Na+-K+ ATPase activity, decreased D1 receptor mediated inhibitory effect on Na+-K+ ATPase activity, decreased D1 receptor expression and increased D1 receptor phosphorylation in RPT cells. The downregulation of D1 receptor expression and function might be due to higher GRK4 expression, because down-regulation of GRK4 by siRNA reversed the D1 receptor expression and function. Due to the role of ROS on D1 receptor dysfunction, we checked ROS levels, and found plasma ROS levels were higher in PM2.5 treated SD rats. Inhibition of ROS by tempol reduced blood pressure and increased sodium excretion in PM2.5 treated SD rats, accompanied by increased the lower D1 receptor expression, and decreased the hyperphosphorylated D1 receptor and GRK4 expression. Conclusions: Long-term exposure of PM2.5 increases blood pressure by decreased D1 receptor expression and function; ROS, via regulation of GRK4 expression, is taken part in the pathogenesis of PM2.5-induced hypertension.

Abstract 412: The Sodium-Glucose Cotransporter 2 Inhibitor Empagliflozin Improves Diabetic Complications in the Streptozotocin Type 1 Diabetes Mellitus Model by Interfering With Glucotoxicity and Rescue of Beta-Cell Function

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Philipp Welschof ◽  
Matthias Oelze ◽  
Swenja Kröller-Schön ◽  
Thomas Jansen ◽  
Michael Hausding ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Type I Diabetes ◽  
Cardiovascular Complications ◽  
Diabetic Rats ◽  
Low Grade ◽  
Type I ◽  
Urinary Glucose ◽  
And Oxidative Stress

Objectives: In diabetes, cardiovascular complications are associated with endothelial dysfunction and oxidative stress. Empagliflozin (Empa), as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i) in clinical development, offers a promising novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with Empa could improve endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated oxidative stress. Research Design and Methods: Type I diabetes in Wistar rats was induced by an intravenous injection of streptozotocin (60 mg/kg). One week after injection Empa was administered via drinking water for 7 weeks. Results: Treatment with Empa (10 and 30 mg/kg/d), showed reduction of blood glucose and a normalization of endothelial dysfunction (aortic rings) in diabetic rats and a reduced oxidative stress in aortic vessels (dihydroethidine staining) and in blood (phorbol ester/zymosan A-stimulated chemiluminescence). Additionally, the pro-inflammatory phenotype and glucotoxicity in diabetic animals was normalized by SGLT2i therapy. Conclusion: In this study we could demonstrate that Empa improves hyperglycemia and prevents the development of endothelial dysfunction and oxidative stress in type 1 diabetic rats. Future studies will investigate the underlying mechanisms of these antioxidant and anti-inflammatory effects with special emphasis on low-grade inflammation, glucotoxicity and oxidative stress, all of which contributes to cardiovascular complications.

Type I diabetes suppresses intracellular calcium ion increase normally evoked by heat stress in rat skeletal muscle

2021 ◽  
Author(s):  
Ryo Ikegami ◽  
Hiroaki Eshima ◽  
Toshiaki Nakajima ◽  
Shigeru Toyoda ◽  
David C. Poole ◽  
...  
Keyword(s):  
Heat Stress ◽  
Protein Expression ◽  
Type I Diabetes ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Type I ◽  
Male Wistar Rats ◽  
Intracellular Calcium Ion ◽  
And Function

Heat stress, via its effects on muscle intracellular Ca2+ concentrations ([Ca2+]i), has been invoked as a putative therapeutic countermeasure to Type 1 diabetes-induced muscle atrophy. Using in vivo muscle preparation we tested the hypothesis that impaired muscle Ca2+ homeostasis in type I diabetic rats is due to attenuated heat stress tolerance mediated via TRPV1. Male Wistar rats were assigned to 1 of 4 groups: 1.control 30oC (CONT 30oC), 2.CONT 40oC, 3.diabetes 30oC (DIA 30oC), 4.DIA 40oC. 40oC was selected because it just exceeds the TRPV1 activation threshold. Spinotrapezius muscles were exteriorized in vivo and loaded with the fluorescent Ca2+ probe Fura-2AM. [Ca2+]i was estimated over 20min using fluorescence microscopy in quiescent muscle held at the required temperature using calibrated heat source applied to the ventral muscle surface. Western blotting was performed to determine the protein expression levels of TRPV1 in spinotrapezius muscle. After 20min of heat stress, the CONT 40oC condition induced a 12.3% [Ca2+]i elevation that was absent from the DIA 40oC or other conditions. Thus, no significant differences were found among DIA 40oC, DIA 30oC and CONT 30oC. TRPV1 protein expression was decreased by 42.0% in DIA compared with CONT (P<0.05) and, unlike CONT, heat stress did not increase TRPV1 phosphorylation. In conclusion, diabetes suppresses TRPV1 protein expression and function and inhibits the elevated myocyte [Ca2+]i evoked normally by heat stress. These results suggest that capsaicin or other therapeutic strategies to increase Ca2+ accumulation via TRPV1 might be more effective than hyperthermic therapy for Type I diabetic patients.

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