Endothelin A (ETA) Receptors Are Involved in Augmented Adrenergic Vasoconstriction and Blunted Nitric Oxide-Mediated Relaxation of Penile Arteries from Insulin-Resistant Obese Zucker Rats

2014 ◽  
Vol 11 (6) ◽  
pp. 1463-1474 ◽  
Author(s):  
Ana Sánchez ◽  
Cristina Contreras ◽  
Pilar Martínez ◽  
Mercedes Muñoz ◽  
Ana Cristina Martínez ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Zucker Rats ◽  
Insulin Resistant ◽  
Obese Zucker Rats ◽  
Endothelin A ◽  
Penile Arteries

scholarly journals Role of Neural NO Synthase (nNOS) Uncoupling in the Dysfunctional Nitrergic Vasorelaxation of Penile Arteries from Insulin-Resistant Obese Zucker Rats

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e36027 ◽  
Author(s):  
Ana Sánchez ◽  
Cristina Contreras ◽  
María Pilar Martínez ◽  
Belén Climent ◽  
Sara Benedito ◽  
...  
Keyword(s):  
No Synthase ◽  
Zucker Rats ◽  
Insulin Resistant ◽  
Obese Zucker Rats ◽  
Penile Arteries

scholarly journals Evidence for altered sensitivity of the nitric oxide/cGMP signalling cascade in insulin-resistant skeletal muscle

1998 ◽  
Vol 329 (1) ◽  
pp. 73-79 ◽  
Author(s):  
E. Martin YOUNG ◽  
Brendan LEIGHTON
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Glucose Utilization ◽  
Phosphodiesterase Inhibitor ◽  
Zucker Rats ◽  
Insulin Resistant ◽  
Cgmp Signalling ◽  
Rat Soleus Muscle ◽  
Obese Zucker Rats

Nitric oxide activates guanylate cyclase to form cGMP, comprising a signalling system that is believed to be a distinct mechanism for increasing glucose transport and metabolism in skeletal muscle. The effects of a selective cGMP phosphodiesterase inhibitor, zaprinast, on basal glucose utilization was investigated in incubated rat soleus muscle preparations isolated from both insulin-sensitive (lean Zucker; Fa/?) and insulin-resistant (obese Zucker; fa/fa) rats. Zaprinast at 27 μM significantly increased cGMP levels in incubated soleus muscle isolated from lean, but not obese, Zucker rats. Muscles were incubated with 14C-labelled glucose and various concentrations of zaprinast (3, 27 and 243 μM). Zaprinast (at 27 and 243 μM) significantly increased rates of net and 14C-labelled lactate release and of glycogen synthesis in lean Zucker rat soleus muscle; glucose oxidation was also increased by 27 μM zaprinast. In addition, regardless of concentration, the phosphodiesterase inhibitor failed to increase any aspect of 14C-labelled glucose utilization in soleus muscles isolated from obese Zucker rats. The maximal activity of nitric oxide synthase (NOS) was significantly decreased in insulin-resistant obese Zucker muscles. Thus the lack of effect of zaprinast in insulin-resistant skeletal muscle is consistent with decreased NOS activity. To test whether there is a defect in insulin-resistant skeletal muscle for endogenous activation of guanylate cyclase, soleus muscles were isolated from both insulin-sensitive and insulin-resistant Zucker rats and incubated with various concentrations of the NO donor sodium nitroprusside (SNP; 0.1, 1, 5 and 15 mM). SNP significantly increased rates of net and 14C-labelled lactate release, as well as glucose oxidation in muscles isolated from both insulin-sensitive and insulin-resistant rats. A decreased response to SNP was observed in the dose-dependent generation of cGMP within isolated soleus muscles from insulin-resistant rats. A possible link between impaired NO/cGMP signalling and abnormal glucose utilization by skeletal muscle is discussed.

Impaired Endothelin Calcium Signaling Coupled to Endothelin Type B Receptors in Penile Arteries from Insulin-Resistant Obese Zucker Rats

2013 ◽  
Vol 10 (9) ◽  
pp. 2141-2153 ◽  
Author(s):  
Cristina Contreras ◽  
Ana Sánchez ◽  
Pilar Martínez ◽  
Belén Climent ◽  
Sara Benedito ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Zucker Rats ◽  
Type B ◽  
Insulin Resistant ◽  
Obese Zucker Rats ◽  
Penile Arteries

Modulation of noradrenaline-induced vasoconstriction in isolated perfused mesenteric arterial beds from obese Zucker rats in the presence and absence of insulin

2002 ◽  
Vol 80 (3) ◽  
pp. 171-179 ◽  
Author(s):  
Yi He ◽  
Kathleen M MacLeod
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Receptor Antagonist ◽  
Vascular Reactivity ◽  
Zucker Rats ◽  
Insulin Resistant ◽  
Significant Difference ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Presence And Absence

The genetically obese Zucker rat (fa/fa) is an insulin-resistant animal model with early-onset severe hyperinsulinemia that eventually develops mild hypertension. Thus, it represents a model in which the effect of hyperinsulinemia – insulin resistance associated with hypertension on vascular reactivity can be examined. The purpose of this study was to investigate the contribution of endogenous nitric oxide (NO) and prostaglandins to reactivity to noradrenaline (NA) in the presence and absence of insulin in mesenteric arterial beds (MAB) from 25-week-old obese Zucker rats and their lean, gender-matched littermates. In the absence of insulin, bolus injection of NA (0.9–90 nmol) produced a dose-dependent increase in perfusion pressure in MAB from both lean and obese rats. Although there was no significant difference in NA pD2 (–log ED50) values, the maximum response of MAB from obese rats to NA was slightly but significantly reduced compared with that of MAB from lean rats. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 300 µM) enhanced and indomethacin (20 µM) inhibited pressor responses to NA in MAB from both obese and lean rats. Perfusion with insulin (200 mU/L, a level similar to that in obese rats in vivo) potentiated only the responses of the obese MAB to the two lowest doses of NA tested (0.9 and 3 nmol). In the presence of L-NMMA, insulin further potentiated the NA response in MAB from obese rats. Indomethacin, the prostaglandin H2/thromboxane A2 receptor antagonist SQ 29548 (0.3 µM), and the nonselective endothelin-1 (ET-1) receptor antagonist bosentan (3 µM) all abolished insulin potentiation of the NA response in obese MAB. These data suggest that concurrent release of NO and vasoconstrictor cyclooxygenase product(s) in MAB from both obese and lean Zucker rats normally regulates NA-induced vasoconstrictor responses. Furthermore, insulin increases the release of contracting cyclooxygenase product(s) and enhances reactivity to low doses of NA in MAB from obese rats. The effects of insulin may be partially mediated by ET-1 via ET receptors and are buffered to some extent by concomitant NO release. This altered action of insulin may play a role in hypertension in this hyperinsulinemic – insulin-resistant model.Key words: hyperinsulinemia, insulin resistance, hypertensive Zucker obese rat, mesenteric arterial bed, noradrenaline.

scholarly journals Simvastatin Does Not Affect Nitric Oxide Generation Increased by Sesame Oil in Obese Zucker Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Martina Cebova ◽  
Radoslava Rehakova ◽  
Michaela Kosutova ◽  
Olga Pechanova
Keyword(s):  
Nitric Oxide ◽  
Side Effects ◽  
Lipid Profile ◽  
Plasma Lipid ◽  
Sesame Oil ◽  
Zucker Rats ◽  
Plasma Lipid Profile ◽  
Protein Expressions ◽  
Obese Zucker Rats ◽  
Oxidative Load

Current treatments for cardiovascular and obesity-associated diseases, such as statin therapy, may be associated with several side effects. Products from food sources with polyphenolic compounds may represent promising agents in the treatment of cardiovascular and metabolic diseases with minimal side effects. Thus, we aimed to study the effect of sesame oil and simvastatin treatment on plasma lipid profile, nitric oxide generation, and oxidative load in obese Zucker rats. 12-week-old male Zucker rats were divided into the control and sesame oil- (1.25 ml/kg/day) treated Zucker lean groups, the control and sesame oil (1.25 ml/kg/day), or simvastatin (15 mg/kg/day) together with sesame oil-treated Zucker fa/fa groups, n=6 in each group. The treatment lasted for 6 weeks. Sesame oil composition and plasma lipid profile were analyzed. Nitric oxide synthase (NOS) activity, endothelial NOS (eNOS), phosphorylated eNOS, and inducible NOS (iNOS) protein expressions were determined in the left ventricle and aorta. Oxidative load, measured as conjugated diene (CD) and thiobarbituric acid reactive substance (TBARS) concentrations, was detected in the liver. Neither sesame oil nor cotreatment with simvastatin affected plasma lipid profile in Zucker fa/fa rats. Sesame oil and similarly cotreatment with simvastatin markedly increased NOS activity and phosphorylated eNOS protein expressions in the left ventricle and aorta of Zucker fa/fa rats. There were no changes in eNOS and iNOS protein expressions within the groups and tissues investigated. Hepatic CD concentration was higher in Zucker fa/fa comparing Zucker lean rats, and sesame oil treatment decreased it significantly. Interestingly, this decrease was not seen after cotreatment with simvastatin. In conclusion, phosphorylation of eNOS and decreased oxidative load may significantly contribute to increase in total NOS activity with potential beneficial properties. Interestingly, simvastatin did not affect NO generation already increased by sesame oil in obese Zucker rats.

scholarly journals Role of nitric oxide in septal coronary arteries of obese Zucker rats

2014 ◽  
Vol 2 (1) ◽  
Author(s):  
Priyanka Prathipati ◽  
Syed Quadri ◽  
Debra Jackson ◽  
Keith Jackson
Keyword(s):  
Nitric Oxide ◽  
Coronary Arteries ◽  
Zucker Rats ◽  
Obese Zucker Rats

Effects of a unique conjugate of α-lipoic acid and γ-linolenic acid on insulin action in obese Zucker rats

2000 ◽  
Vol 278 (2) ◽  
pp. R453-R459 ◽  
Author(s):  
J. Anthony Peth ◽  
Tyson R. Kinnick ◽  
Erik B. Youngblood ◽  
Hans J. Tritschler ◽  
Erik J. Henriksen
Keyword(s):  
Fatty Acid ◽  
Essential Fatty Acid ◽  
Glucose Transport ◽  
Lipoic Acid ◽  
Insulin Action ◽  
Whole Body ◽  
Zucker Rats ◽  
Additive Effects ◽  
Insulin Resistant ◽  
Obese Zucker Rats

The purpose of this study was to assess the individual and interactive effects of the antioxidant α-lipoic acid (LPA) and the n-6 essential fatty acid γ-linolenic acid (GLA) on insulin action in insulin-resistant obese Zucker rats. LPA, GLA, and a unique conjugate consisting of equimolar parts of LPA and GLA (LPA-GLA) were administered for 14 days at 10, 30, or 50 mg ⋅ kg body wt− 1 ⋅ day− 1. Whereas LPA was without effect at 10 mg/kg, at 30 and 50 mg/kg it elicited 23% reductions ( P < 0.05) in the glucose-insulin index (the product of glucose and insulin areas under the curve during an oral glucose tolerance test and an index of peripheral insulin action) that were associated with significant increases in insulin-mediated (2 mU/ml) glucose transport activity in isolated epitrochlearis (63–65%) and soleus (33–41%) muscles. GLA at 10 and 30 mg/kg caused 21–25% reductions in the glucose-insulin index and 23–35% improvements in insulin-mediated glucose transport in epitrochlearis muscle. The beneficial effects of GLA disappeared at 50 mg/kg. At 10 and 30 mg/kg, the LPA-GLA conjugate elicited 29 and 38% reductions in the glucose-insulin index. These LPA-GLA-induced improvements in whole body insulin action were accompanied by 28–63 and 38–57% increases in insulin-mediated glucose transport in epitrochlearis and soleus muscles and resulted from the additive effects of LPA and GLA. At 50 mg/kg, the metabolic improvements due to LPA-GLA were substantially reduced. In summary, these results indicate that the conjugate of the antioxidant LPA and the n-6 essential fatty acid GLA elicits significant dose-dependent improvements in whole body and skeletal muscle insulin action on glucose disposal in insulin-resistant obese Zucker rats. Moreover, these actions of LPA-GLA are due to the additive effects of its individual components.

P356 GLUCOSE-LOWERING EFFECT OF APPLE POLYPHENOLS IN INSULIN RESISTANT OBESE ZUCKER RATS

2008 ◽  
Vol 3 ◽  
pp. 180
Author(s):  
M. Manzano ◽  
M.L. Jimenez ◽  
R. Rueda ◽  
J.M. Lopez-Pedrosa
Keyword(s):  
Zucker Rats ◽  
Glucose Lowering ◽  
Insulin Resistant ◽  
Lowering Effect ◽  
Glucose Lowering Effect ◽  
Obese Zucker Rats

scholarly journals Enhanced cyclooxygenase 2‐mediated vasodilatation in coronary arteries from insulin resistant obese Zucker rats

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
DOLORES PRIETO ◽  
ANA SÁNCHEZ PINA ◽  
CRISTINA CONTRERAS ◽  
NURIA VILLALBA ◽  
MARTINEZ PILAR
Keyword(s):  
Coronary Arteries ◽  
Cyclooxygenase 2 ◽  
Zucker Rats ◽  
Insulin Resistant ◽  
Obese Zucker Rats
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