Norepinephrine storage, distribution, and release in diabetic cardiomyopathy

Ganguly, Pallab K.; Beamish, Robert E.; Dhalla, Ken S.; Innes, I. R.; Dhalla, Naranjan S.

doi:10.1152/ajpendo.1987.252.6.e734

Cited by 62 publications

(60 citation statements)

References 2 publications

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“…Table 2 summarizes these changes. Increased levels of NA have been reported in many viscera 11,[24][25][26] in STZ diabetes, but there are not many studies that cover the time course of these experiments. 12 Some workers confine their studies of STZ diabetes to the first 8 weeks or so, and if the changes we report have a functional significance, it is unlikely that changes in function related to sympathetic nerve activity will be seen much before 8-10 weeks of hyperglycaemia have occurred.…”

Section: Discussionmentioning

confidence: 99%

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat

et al. 2007

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The noradrenaline (NA) concentration in the rat corpus cavernosum (CC) increased to approximately 350% of control values after about 8 weeks of hyperglycaemia induced by the intraperitoneal injection of streptozotocin (STZ) at 10 weeks of age. These changes were maintained for at least a further 32 weeks of hyperglycaemia and occurred without any significant change in the weight in the tissue. Smaller but significant increases in NA concentration occurred in the glans penis (GP) reaching 150-175% of the control levels during the period of prolonged hyperglycaemia. In contrast, there was no significant change in the NA concentration in the penile urethra. Measurements have also been made that relate to changes in the synthesis and reuptake of NA in the CC during the period during which high NA concentration is maintained. Immunohistochemical studies for the synthetic enzyme tyrosine hydroxylase in the CC indicate that the intensity of staining in the tissue had increased after 10, 20 and 32 weeks of hyperglycaemia, relative to the tissues from control animals. Dilated nerve fibres and engorged endings were present in the CC of the diabetic animals at these times. Reuptake of tritiated NA by the terminal axonal membranes in the CC was raised to 181% of control values after 12 weeks of hyperglycaemia (Po0.05), but later declined to values that are not significantly different from the control levels (after 26 and 64 weeks of hyperglycaemia). There are few studies of the effects of prolonged diabetes on functional aspects of sympathetic postganglionic neurones in the CC, and this paper suggests that the changes described represent remodelling of noradrenergic axonal terminals starting about after 8-10 weeks of hyperglycaemia; this delay in onset of the neuropathic changes is also a feature of type I diabetes in humans.

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Section: Discussionmentioning

confidence: 99%

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat

et al. 2007

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“…Similarly, it has been demonstrated that cardiac noradrenaline content is increased in diabetic rats (31). In addition, it was reported that noradrenaline turnover, uptake, synthesis, and release are all enhanced in diabetic cardiomyopathy (32,33). Therefore, chronically high concentrations of noradrenaline in diabetes may contribute to the selective downregulation of ␤ 1 -ARs, as the affinity of noradrenaline is lower for ␤ 2 -ARs.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Diabetes on Expression of β1-,β2-, and β3-Adrenoreceptors in Rat Hearts

et al. 2001

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Diabetic hearts exhibit decreased responsiveness to stimulation by ␤-adrenoreceptor (␤-AR) agonists. This decrease in activity may be due to changes in expression and/or signaling of ␤-AR. Recently we showed that right atrial strips from 14-week streptozotocin (STZ)-induced diabetic rat hearts exhibit decreased responsiveness to ␤ 1 -AR agonist stimulation, but not to ␤ 2 -AR agonist. In the present study, we investigated the effects of long-term diabetes on the expression of cardiac ␤ 1 -, ␤ 2 -, and ␤ 3 -ARs and looked at whether these changes could be restored with insulin treatment. Using reverse transcription-polymerase chain reaction (RT-PCR), PAGE, and Western blot analysis, we found that ␤ 1 -AR mRNA and protein levels decreased by 34.9 ± 5.8 and 44.4 ± 5.8%, respectively, in 14 week-STZtreated diabetic rat hearts when compared with agematched controls. On the other hand, mRNA levels encoding ␤ 2 -and ␤ 3 -ARs increased by 72.5 ± 16.6 and 97.3 ± 26.1%, respectively. Although the latter translated into a proportional increase in ␤ 3 -AR protein levels (100.0 ± 17.0%), ␤ 2 -AR protein levels decreased to 82.6 ± 1.1% of control. Insulin treatment for 2 weeks, after 12 weeks of untreated diabetes, partially restored ␤ 1 -AR mRNA and protein levels to 60.1 ± 8.4 and 83.2 ± 5.0%, respectively, of control. Although insulin treatment minimally attenuated the rise in mRNA levels encoding ␤ 2 -and ␤ 3 -ARs, the steady-state levels of these proteins returned to near control values. These data suggest that the decreased responsiveness of diabetic hearts to stimulation of ␤-AR agonists may be due to a decrease in ␤ 1 -AR and an increase ␤ 3 -AR expression. Diabetes 50: [455][456][457][458][459][460][461] 2001

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“…However, some investigators have reported increased cardiac norepinephrine uptake and increased cardiac sympathetic nerve activity in rats with STZ-induced DM. 50, 51 An increase in cardiac sympathetic activity accelerates MIBG turnover at nerve terminals, resulting in decreased cardiac MIBG accumulation in delayed images. However, the present study found the same cardiac MIBG WR in the rats, regardless of fluvastatin administration.…”

Section: Cardiac Mibg Accumulationmentioning

confidence: 99%

Fluvastatin Attenuates Diabetes-Induced Cardiac Sympathetic Neuropathy in Association With a Decrease in Oxidative Stress

Matsuki

Nozawa

Igarashi

et al. 2010

Circ J

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Background: Increased oxidative stress might contribute to diabetic (DM) neuropathy, so the effects of longterm treatment with fluvastatin (FL) on myocardial oxidative stress and cardiac sympathetic neural function were investigated in diabetic rats.Methods and Results: FL (10 mg · kg -1 · day -1 , DM-FL) or vehicle (DM-VE) was orally administered for 2 weeks to streptozotocin-induced DM rats. Cardiac oxidative stress was determined by myocardial 8-iso-prostaglandin F2α (PGF2α) and NADPH oxidase subunit p22 phox mRNA expression. Sympathetic neural function was quantified by autoradiography using 131 I- and 125 I-metaiodobenzylguanidine (MIBG). FL did not affect plasma glucose levels but remarkably decreased PGF2α levels compared with DM-VE rats (13.8±9.2 vs 175.0±93.9 ng/g tissue), although PGF2α levels were below the detection limit in non-DM rats. FL significantly reduced myocardial p22 phox mRNA expression. Cardiac 131 I-MIBG uptake was lower in DM-VE rats than in non-DM rats, but the decrease was attenuated in DM-FL rats (1.31±0.08, 1.88±0.22, and 1.58±0.18 %kg dose/g, respectively, P<0.01). Cardiac MIBG clearance was not affected by the induction of DM or by FL, indicating that the reduced MIBG uptake in DM rats might result from impaired neural function. Diabetes-Induced Cardiac NeuropathyExperimental Animals DM was induced in male Wistar rats weighing 250-300 g by an intraperitoneal injection of 65 mg/kg of streptozotocin (STZ, n=40). Non-DM control rats (n=14) were not injected with STZ. The rats with glucose levels >250 mg/dl at 1 week after STZ injection were considered diabetic (n=28) and used in the experiments. Two weeks later, fluvastatin (10 mg · kg -1 · day -1 , n=14) or vehicle (DM controls: 0.1% carboxymethyl cellulose, n=14) was orally administered by gavage for 2 weeks. Standard rat chow and tap water were provided ad libitum throughout the study.Systolic blood pressure and heart rate were measured using an indirect tail-cuff method (BP-98A, Softron) and lipid peroxides (LPO) in plasma were determined using a hemoglobin-methylene blue method that selectively detects the absolute quantity of LOOH. Cardiac oxidative stress was then assessed as the levels of 8-isoprostaglandin F2α (PGF2α) and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase subunit p22 phox mRNA expression, and cardiac sympathetic neural function was assessed using 131 I-and 125 Ilabeled MIBG.Radioactive MIBG Tracers FUJIFILM RI Pharma Co Ltd (Tokyo, Japan) prepared and supplied 131 I-and 125 I-labeled MIBG at a radiochemical purity >98%, and specific activity of 30-70 GBq/mmol. Cardiac MIBG AccumulationDual-tracer autoradiography proceeded as described. 22,23 Briefly, 0.37 MBq of 125 I-MIBG was injected via the external jugular vein under pentobarbital sodium anesthesia (30 mg/kg, ip). Two hours later, 1.85 MBq of 131 I-MIBG was intravenously injected and 30 min thereafter, the heart was removed and washed in cold saline. Specimens were frozen in isopentane, cooled in dry ice, embedded in methyl cellulose and cut in...

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Norepinephrine storage, distribution, and release in diabetic cardiomyopathy

Cited by 62 publications

References 2 publications

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat

The Effect of Diabetes on Expression of β1-,β2-, and β3-Adrenoreceptors in Rat Hearts

Fluvastatin Attenuates Diabetes-Induced Cardiac Sympathetic Neuropathy in Association With a Decrease in Oxidative Stress

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