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Nondiabetic Rats (nondiabetic + rat)
Selected AbstractsAccelerated DNA fragmentation of the denture-bearing mucosal epithelium in an animal model of diabetesJOURNAL OF ORAL REHABILITATION, Issue 4 2001Y. Maruo This study examined the effect of masticatory pressure transmitted directly to the hard palate mucosa on the final stage of terminal differentiation of keratinizing system of rats with and without streptozotocin-induced diabetes mellitus. In the nondiabetic rats with masticatory pressure, the number of terminal-deoxynucleotidyl-transferase-mediated deoxyuridine-triphospate-biotin nick end labelling (TUNEL) positive cells tended to increase about twice as much as in the nondiabetic rats without pressure with and without denture. A similar tendency of increase was observed in the diabetic rats without pressure. The synergy of the mechanical pressure and diabetic condition for 2 weeks greatly accelerated the DNA fragmentation, showing 8-fold increase in TUNEL positive cells over the normal control, and caused exfoliation of the stratum corneum. A 4-week exposure of diabetics to the masticatory pressure induced laminar splitting in the midst of the spinosum. Some cells in the stratum granulosum exhibited a sign of DNA fragmentation when laminar splitting took place in the vital cell layer. Premature DNA fragmentation may disturb the adhesion between spinosum cells and prevent the maturation of stratum corneum. Increase in Bax protein-like immunoreactivity in these epithelial cells as revealed by immunocytochemistry may underlie the premature DNA fragmentation in the oral masticatory epithelium under pressure in diabetic patients. [source] Inhibition of NAD(P)H Oxidase Alleviates Impaired NOS-dependent Responses of Pial Arterioles in Type 1 Diabetes MellitusMICROCIRCULATION, Issue 7 2006WILLIAM G. MAYHAN ABSTRACT Objective: The goal was to identify the role of NAD(P)H oxidase in cerebrovascular dysfunction in type 1 diabetes mellitus (T1D). Methods: In a first series of studies, rats were assigned to nondiabetic, diabetic (streptozotocin; 50 mg/kg IP), nondiabetic-apocynin (40 mg/kg/day in drinking water)-treated and diabetic-apocynin-treated groups. Two to three months later, the authors examined in vivo responses of pial arterioles to nitric oxide synthase (NOS)-dependent (acetylcholine and adenosine diphosphate (ADP)) and -independent (nitroglycerin) agonists. Next, they used Western blot analysis to examine protein levels for subunits of NAD(P)H oxidase in cerebral microvessels and parietal cortex tissue of nondiabetic and diabetic rats. Finally, they measured superoxide production by parietal cortex tissue in nondiabetic and diabetic rats. Results: Acetylcholine- and ADP-induced dilatation of pial arterioles was impaired in diabetic compared to nondiabetic rats. In addition, while apocynin did not alter responses in nondiabetic rats, apocynin alleviated T1D-induced impairment of NOS-dependent vasodilatation. In addition, p47phox and gp91phox proteins were elevated in cerebral microvessels and parietal cortex tissue, respectively, of diabetic compared to nondiabetic rats. Further, basal production of superoxide was increased in diabetic compared to nondiabetic rats and apocynin decreased this basal production. Conclusions: The findings suggest that T1D impairs NOS-dependent reactivity of cerebral arterioles by a mechanism related to the formation of superoxide via activation of NAD(P)H oxidase. [source] Nebivolol Dilates Human Penile Arteries and Reverses Erectile Dysfunction in Diabetic Rats through Enhancement of Nitric Oxide SignalingTHE JOURNAL OF SEXUAL MEDICINE, Issue 8 2010Javier Angulo PhD ABSTRACT Introduction., Traditional beta-blockers have sometimes been associated with erectile dysfunction (ED). Nebivolol is a cardioselective ,1 -adrenoceptor antagonist that promotes vasodilation through a nitric oxide (NO)-dependent mechanism. Aim., We evaluated the effects of nebivolol on the NO/cyclic guanosine monophosphate (cGMP) signaling pathway, on erectile function and dysfunction, and in human penile vascular tissues. Methods., Erectile response to cavernosal nerve electrical stimulation in control and diabetes-induced ED rats were evaluated, along with serum nitrite/nitrate (NOx) concentration and plasma/tissue cGMP levels. Endothelium-dependent and sildenafil-induced relaxation of isolated human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) were also determined. Main Outcome Measures., The effects of nebivolol on erectile function and dysfunction and on NO/cGMP-mediated responses. Results., Treatment with nebivolol significantly potentiated erectile response in control rats, regardless of its effects on blood pressure. Nebivolol increased NOx and plasma cGMP by 3-fold and 2.75-fold, respectively, and significantly augmented the elevation of plasma cGMP produced by sildenafil. Nebivolol enhanced endothelium-dependent and sildenafil-induced relaxations of HCC tissue, and produced endothelium-dependent vasodilation of HPRA. Nebivolol, but not atenolol, significantly improved erectile response in diabetic rats (51.6%, 53.2%, and 87.1% of response at 3 Hz in nondiabetic rats, for vehicle-treated, atenolol-treated, and nebivolol-treated diabetic rats, respectively); after sildenafil administration, ED was completely reversed in nebivolol-treated diabetic rats (69.6% and 112% for diabetic rats treated with sildenafil and nebivolol plus sildenafil, respectively). Accordingly, nebivolol restored systemic NOx levels and cGMP content in penile tissue from these animals. Conclusions., Nebivolol in vivo activated the NO/cGMP pathway, enhanced erectile response and reversed ED in diabetic rats. Moreover, nebivolol in vitro potentiated NO/cGMP-mediated relaxation of human erectile tissues. These effects may account for the low incidence of ED in nebivolol-treated hypertensive patients. Nebivolol therefore may have utility in the treatment of ED, particularly ED associated with diabetes. Angulo J, Wright HM, Cuevas P, González-Corrochano R, Fernández A, Cuevas B, La Fuente JM, Gupta S, and de Tejada IS. Nebivolol dilates human penile arteries and reverses erectile dysfunction in diabetic rats through enhancement of nitric oxide signaling. J Sex Med 2010;7:2681,2697. [source] ORIGINAL RESEARCH,BASIC SCIENCE: Enhancement of Both EDHF and NO/cGMP Pathways Is Necessary to Reverse Erectile Dysfunction in Diabetic RatsTHE JOURNAL OF SEXUAL MEDICINE, Issue 3 2005Javier Angulo PhD ABSTRACT Aims and Methods., Phosphodiesterase 5 (PDE5) inhibitors are less effective in the treatment of erectile dysfunction (ED) in diabetic men than in nondiabetic patients. We have evaluated the effects of sildenafil, a PDE5 inhibitor that enhances the nitric oxide (NO)/cGMP pathway, calcium dobesilate (DOBE), which potentiates endothelium-derived hyperpolarizing factor (EDHF)-mediated responses and the combination of both on erectile responses elicited by cavernosal nerve electrical stimulation (CNES) in a rat model of ED after 8 weeks of streptozotocin-induced diabetes. Results., After 8 weeks of diabetes, erectile responses to CNES were significantly decreased in diabetic animals compared with nondiabetic time controls. While intravenous administration of sildenafil (0.3 mg/kg) or DOBE (10 mg/kg), individually, enhanced erectile responses in nondiabetic rats (214.7 ± 34.1% and 268.5 ± 30.1% of control response at 1 Hz, respectively), each failed to significantly enhance erectile responses in diabetic rats. Only when administered in combination did DOBE and sildenafil markedly potentiate erectile responses in these animals (380.1 ± 88.6% of control response at 1 Hz), completely restoring erectile function. Conclusions., These findings emphasize the importance of NO/cGMP and EDHF pathways for normal erectile function. They also give support to the in vitro observation that diabetes impairs NO and EDHF-dependent responses, precluding the complete recovery of erectile function with PDE5 inhibitors and explaining the relatively poor clinical response of diabetic men with ED to PDE5 inhibition. Finally, our study suggests that a pharmacological approach that combines enhancement of NO/cGMP and EDHF pathways could be necessary to treat ED in many diabetic men. [source] Uncontrolled Hemorrhage in Insulin-dependent Diabetic RatsACADEMIC EMERGENCY MEDICINE, Issue 8 2009Eric J. Morley MD Abstract Objectives:, Diabetes mellitus (DM) is a known risk factor for higher morbidity and mortality after trauma. The authors tested the hypothesis that there is a difference in the response to uncontrolled hemorrhage between normal euglycemic rats and insulin-dependent diabetic rats. Methods:, Thirty-one adult male Sprague-Dawley rats were used in this study. Fifteen streptozocin (STZ)-injected rats became diabetic (DM+) 2 weeks after treatment. Sixteen rats served as nondiabetic controls (DM,). All rats were anesthetized with Althesin and their femoral arteries were catheterized via cutdown, allowing continuous monitoring of vital signs. Sixteen (eight DM,, eight DM+) rats underwent uncontrolled hemorrhage by 75% tail amputation. Fifteen (eight DM,, seven DM+) rats served as nonhemorrhage controls. The mean arterial pressure (MAP), lactate, and cumulative hemorrhage volume per 100 g were measured prehemorrhage and then every 15 minutes posthemorrhage for 2 hours. Data were reported as mean ± standard deviation. Interval data were analyzed by analysis of variance (two tails, , = 0.05). Results:, Prehemorrhage glucose was significantly higher (p < 0.001) in the DM+ (357.9 ± 22.2 mg/dL) versus DM, (125.7 ± 9.7 mg/dL) rats. At baseline, there was no significant difference in weight, MAP, or lactate between DM+ and DM, rats. Body-weight-adjusted mean cumulative hemorrhage volume was significantly greater (p < 0.04) in diabetic rats (2.52 ± 0.15 cm3/100 g body weight) than the nondiabetic rats (1.86 ± 0.25 cm3/100 g body weight). Conclusions:, Compared to nondiabetic rats, diabetic rats suffered a greater blood loss after the same uncontrolled vascular injury. [source] | ||||||||||