Nitric oxide mediates increased prostaglandin E production by oocyte - cumulus complexes in the non-insulin-dependent diabetic rat

1998 ◽  
Vol 10 (2) ◽  
pp. 185 ◽  
Author(s):  
Alicia Jawerbaum ◽  
Elida T. Gonzalez ◽  
Virginia Novaro ◽  
Alicia Faletti ◽  
Martha A. F. Gimeno
Keyword(s):  
Nitric Oxide ◽  
Diabetic Rats ◽  
No Synthase ◽  
Diabetic Rat ◽  
Prostaglandin E ◽  
Basal Secretion ◽  
No Donors ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic ◽  
Synthase Inhibitor

Previous work described an increase in prostaglandin E (PGE) production by oocyte–cumulus complexes (OVA) obtained from non-insulin-dependent diabetic rats. More recently, it has been found that in control OVA nitric oxide (NO) mediates hCG-induced PGE secretion. To determine whether increases in PGE secretion by diabetic OVA are mediated by NO, the present study has evaluated the secretion of PGE by diabetic OVA, cultured in the absence or presence of hCG, NO donors (sodium nitroprusside (NP) and 3-morpholino-sydnonimine-hydrochloride (SIN–1)), and a NO synthase inhibitor (NG monomethyl-L-arginine; L-NMMA). hCG, NP and SIN–1 increased PGE secretion by diabetic OVA. L-NMMA did not modify basal secretion of PGE by control OVA but lowered PGE production in diabetic OVA to control values. L-NMMA prevented the hCG-induced PGE accumulation in control and diabetic OVA, and the quantities of PGE produced were similar to those of control OVA but lower than in diabetic OVA incubated in the absence of hCG. The effect of L-NMMA seems to be specific since NG monomethyl-D-arginine had no effect. NO synthase activity was higher in diabetic ovaries than in controls. The present results suggest that NO mediates the increased PGE production by diabetic OVA, probably a result of overproduction of NO.

Uterine nitric oxide and prostaglandin E during embryonic implantation in non-insulin-dependent diabetic rats

1998 ◽  
Vol 10 (3) ◽  
pp. 217 ◽  
Author(s):  
V. Novaro ◽  
A. Jawerbaum ◽  
A. Faletti ◽  
M. A. F. Gimeno ◽  
E. T. González
Keyword(s):  
Nitric Oxide ◽  
Embryo Implantation ◽  
Implantation Rate ◽  
Diabetic Rats ◽  
Control Group ◽  
Prostaglandin E ◽  
Compensatory Mechanism ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic ◽  
Oxide Synthase

In the process of embryo implantation in the rat, both nitric oxide and prostaglandins act as vascular and myometrial regulators. The aim of the present work was to evaluate the effect of diabetes on the synthesis of both agents during embryo implantation. In diabetic rats, uterine activity of the enzyme nitric oxide synthase and prostaglandin E production were increased during peri-implantation compared to the control group (P < 0·05 and P < 0·001, respectively). Both parameters showed a prolonged increase in temporal profile during peri-implantation days. Local production of nitric oxide and prostaglandin E in the implantation sites was higher in diabetic rats (P < 0·05), but the intersite : site ratio was similar to that of the control group. On the other hand, the implantation rate and the timing of the beginning of this process were not altered in the diabetic group. These results suggest that the vasoactive modulators of the implantation process, nitric oxide and prostaglandins, are increased in this diabetic pathology, and that this increase is probably functioning as a compensatory mechanism, so as to allow an unaltered rate of embryo implantation in this model. Extra keyword: diabetes mellitus.

Abstract P153: Downregulation of Neuronal Nitric Oxide Synthase Within the Paraventricular Nucleus in Insulin Dependent Diabetic Akita Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Neeru M Sharma ◽  
Paras K Mishra ◽  
Kaushik P Patel
Keyword(s):  
Nitric Oxide ◽  
Paraventricular Nucleus ◽  
Renin Angiotensin System ◽  
Diabetic Rats ◽  
Ang Ii ◽  
Protein Levels ◽  
Catalytically Active ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic ◽  
Akita Mice

Activation of both renin-angiotensin- system (RAS) and sympathetic system are the primary etiologic events in the development of hypertension in diabetes mellitus (DM). However, the precise mechanisms for sympathetic activation in DM have not been elucidated. Our previous studies have demonstrated that neuronal nitric oxide (nNOS) expression and nitric oxide (NO) mediated inhibition of sympathetic nerve activity (SNA) is markedly reduced in the paraventricular nucleus (PVN) of streptozotocin-induced diabetic rats. We have further demonstrated that Angiotensin II (Ang II) via Ang II type 1 receptors (AT 1 R) modulates the expression of nNOS in the PVN, which augments sympathetic outflow. Here we hypothesized that DM-linked hypertension and cardiovascular dysregulation is due to the reduction in nNOS with the PVN. To test the hypothesis, we used Ins2 +/- Akita (a spontaneous, insulin dependent genetic diabetic murine model) which showed an increase in systolic blood pressure at the age of 14 weeks compared to corresponding C57BL/6J (WT) mice with concomitant decreased expression of nNOS (0.75±0.05 WT vs. 0.43±0.11* Akita) in the PVN. Further, Akita mice had increased expression of ACE (angiotensin converting enzyme) (WT 0.34±0.04 vs. Akita 0.58±0.05*) and AT 1 R (WT 0.29±0.09 vs. Akita 0.49±0.03*) and decreased expression of ACE2 (0.27±0.03 WT vs. 0.17±0.05* Akita) and Mas receptor (WT 0.77±0.07 vs. Akita 0.46±0.02*), suggesting an imbalance in the excitatory and protective arms of RAS. Moreover, we found increased protein levels of PIN (a protein inhibitor of nNOS, known to dissociate catalytically active nNOS dimers to monomers) (WT 0.71±0.09 vs. Akita 1.75±0.08) with 72 percent decrease in dimer/monomer ratio of nNOS (WT 0.19±0.0 vs. Akita 0.11±0.04) in the PVN of Akita mice. Taken together, our studies suggest that accumulation of PIN, mediated by activation of the excitatory arm of RAS, leads to a decrease in the active dimeric form of nNOS resulting in reduced NO causing an over-activation of the sympathetic drive, leading to hypertension in DM. 1

Nitric oxide mediates human chorionic gonadotrophin-induced prostaglandin E generation in rat oocyte - cumulus complexes

1997 ◽  
Vol 9 (4) ◽  
pp. 391 ◽  
Author(s):  
Alicia Jawerbaum ◽  
Elida T. Gonzalez ◽  
Alicia Faletti ◽  
Virginia Novaro ◽  
Martha A. F. Gimeno
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
No Synthase ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Prostaglandin E ◽  
No Donors ◽  
Nos Inhibitors ◽  
Preovulatory Follicles

To determine whether nitric oxide (NO) generation mediates human chorionic gonadotrophin (hCG)-induced prostaglandin E (PGE) secretion by oocyte–cumulus complexes (OCC), the secretion of PGE by cultured rat OCC in the presence of NO donors and NO synthase (NOS) inhibitors was characterized. NO donors (sodium nitroprusside and 3-morpholino-sydnonimine- hydrochloride) increased PGE accumulation in OCC to values similar to those obtained in the presence of hCG. The three NOS inhibitors tested (N G -nitro-L-arginine methyl ester, NG -monomethyl-L-arginine and aminoguanidine) prevented the hCG-induced PGE accumulation in cultured OCC. This effect appears to be specific since D-enantiomers NG -nitro-D-arginine methyl ester and NG -monomethyl-D-arginine had no effect. The present results suggest that NO mediates the hCG-induced accumulation of PGE in rat OCC, a process which may occur in vivo in preovulatory follicles prior to ovulation.

Increased prostaglandin E generation and enhanced nitric oxide synthase activity in the non-insulin-dependent diabetic embryo during organogenesis

1998 ◽  
Vol 10 (2) ◽  
pp. 191 ◽  
Author(s):  
Alicia Jawerbaum ◽  
Elida T. Gonzalez ◽  
Virginia Novaro ◽  
Alicia Faletti ◽  
Debora Sinner ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Congenital Abnormalities ◽  
Prostaglandin E ◽  
No Donor ◽  
Insulin Dependent ◽  
Nos Inhibitor ◽  
Insulin Dependent Diabetic ◽  
Oxide Synthase

Embryonic development, prostaglandin E (PGE) generation and nitric oxide synthase (NOS) activity during organogenesis were evaluated in an experimental rat model of non-insulin- dependent diabetes (NIDD) generated by neonatal administration of streptozotocin. Gross malformations were detected in 5% of NIDD embryos and these embryos were all non-viable; in the other 95%, growth was retarded but no congenital abnormalities were found. Control embryos were all alive and not malformed. The NIDD 11-day embryos secreted more PGE into the incubation medium than did controls. The NO donor SIN–1 increased PGE production in both control and NIDD embryos. A NOS inhibitor (L-NMMA) reduced PGE generation in both experimental groups, suggesting a modulatory role of NO on embryonic PGE production. Activity of NOS was higher in NIDD 11-day embryos than in controls. Treatment in vivo of control and NIDD rats (Days 7–11 of gestation) with a NOS inhibitor (L-NAME; 5 mg kg-1 i.p.) reduced embryonic PGE production and induced a higher resorption rate and an increase in neural-tube defects. The results suggest that NO modulates PGE generation in the organogenetic embryo. In the NIDD model, overproduction of NO is observed, this NO probably enhancing embryonic PGE production. The relationship between PGE generation and the appearance of congenital abnormalities is discussed.

Diminished levels of prostaglandin E in type I diabetic oocyte - cumulus complexes. Influence of nitric oxide and superoxide dismutase

1999 ◽  
Vol 11 (2) ◽  
pp. 105 ◽  
Author(s):  
Pustrovh Carolina ◽  
Alicia Jawerbaum ◽  
Sinner Debora ◽  
Perotti Christian ◽  
Martha A. F. Gimeno ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Type I Diabetes ◽  
Diabetic Rats ◽  
Nitric Oxide Donor ◽  
Diabetic Rat ◽  
Prostaglandin E ◽  
Type I ◽  
Free Oxygen Radicals ◽  
Type Ii

In the present work the prostaglandin E (PGE) production by ovulated, immature and in vitromatured oocyte–cumulus complexes (OCC) was evaluated in a rat model of type I diabetes induced by streptozotocin (60 mg kg–1). A diminished number of ovulated OCC were found in the type I diabetic rat. In contrast to the increment in PGE generation found previously in OCC and embryos from type II diabetic rats, it was found that PGE production by type I diabetic OCC was diminished in comparison with the controls. Nitric oxide synthase (NOS) activity is enhanced in proestrous ovaries from type I diabetic rats, but cGMP levels are diminished. SIN-1 (300 µМ), a nitric oxide donor, significantly enhanced PGE generation by control OCC, but was unable to modify the PGE levels in type I diabetic OCC. L-NMMA, a nitric oxide inhibitor that diminished PGE values in type II diabetic OCC, did not modify PGE generation in either control and type I diabetic OCC. Superoxide dismutase (SOD, 1000 U mL–1), and SOD (1000 U mL–1) plus SIN-1 (300 µМ), enhanced PGE generation by both control and diabetic OCC. The present results suggest that even when nitric oxide (NO) is overproduced in diabetic ovaries, the NO–PGE pathway is impaired in type I diabetic OCC. As SOD additions are able to increase PGE generation by diabetic OCC, high concentrations of free oxygen radicals might be quenching the NO, impairing its physiological functions.

scholarly journals Ischaemic Preconditioning Suppresses Necrosis of Adipocutaneous Flaps in a Diabetic Rat Model Regardless of the Manner of Preischaemia Induction

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Christian Ottomann ◽  
Markus Küntscher ◽  
Bernd Hartmann ◽  
Vlado Antonic
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Ischaemic Preconditioning ◽  
Skin Flaps ◽  
Tissue Necrosis ◽  
No Donors ◽  
Patients With Diabetes ◽  
Synthase Inhibitor ◽  
Diabetic Rat Model

Ischaemic insult in the skin flaps is a major problem in reconstructive surgery particularly in patients with diabetes mellitus. Here, we sought to investigate the effectiveness of ischaemic preconditioning (IP) on diabetic skin flaps in rat animal model. Hundred Wistar rats (90 streptozotocin treated animals and 10 nondiabetic controls) were used. Diabetes mellitus was confirmed by measuring glucose level in blood, HbA1c, and ketonuria. We used blood vessel clamping, hind limb tourniquet, and NO donors (Spermine/NO complex) to induce short-term ischaemia of tissues that will be excised for skin flaps. Animals were followed for 5 days. Flaps were photographed at day 5 and percent of necrosis was determined using planimetry. Significant decrease in percent of necrotic tissue in all groups that received preconditioning was observed. Results show that ischaemic preconditioning suppresses flap necrosis in diabetic rats irrespective of direct or remote tissue IP and irrespective of chemically or physically induced preischaemia. Spermine/NO complex treatment 10 minutes after the flap ischaemia suppressed tissue necrosis. Treatment with NO synthase inhibitor L-NAME reversed effects of IP showing importance of NO for this process. We show that IP is a promising approach for suppression of tissue necrosis in diabetic flaps and potential of NO pathway as therapeutic target in diabetic flaps.

scholarly journals Sex-specific vascular responses of the rat aorta: effects of moderate term (intermediate stage) streptozotocin-induced diabetes

2016 ◽  
Vol 94 (4) ◽  
pp. 408-415 ◽  
Author(s):  
Xiaoyuan Han ◽  
Sonali Shaligram ◽  
Rui Zhang ◽  
Leigh Anderson ◽  
Roshanak Rahimian
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Mrna Expression ◽  
Intermediate Stage ◽  
Diabetic Rats ◽  
Female Rats ◽  
Diabetic Rat ◽  
Male And Female ◽  
Male And Female Rats ◽  
Oxide Synthase

Hyperglycemia affects male and female vascular beds differently. We have previously shown that 1 week after the induction of diabetes with streptozotocin (STZ), male and female rats exhibit differences in aortic endothelial function. To examine this phenomenon further, aortic responses were studied in male and female rats 8 weeks after the induction of diabetes (intermediate stage). Endothelium-dependent vasodilation (EDV) to acetylcholine (ACh) was measured in phenylephrine (PE) pre-contracted rat aortic rings. Concentration response curves to PE were generated before and after L-NAME, a nitric oxide synthase (NOS) inhibitor. Furthermore, mRNA expression of endothelial nitric oxide synthase (eNOS) and NADPH oxidase subunit (Nox1) were determined. At 8 weeks, diabetes impaired EDV to a greater extent in female than male aortae. Furthermore, the responsiveness to PE was significantly enhanced only in female diabetic rats, and basal NO, as indicated by the potentiation of the response to PE after L-NAME, was reduced in female diabetic rat aortae to the same levels as in males. In addition, eNOS mRNA expression was decreased, while the Nox1 expression was significantly enhanced in diabetic female rats. These results suggest that aortic function in female diabetic rats after 8 weeks exhibits a more prominent impairment and that NO may be involved.

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