Interactions between nitric oxide and renal nerves in the excretion of a saline load in obese Zucker rats

The present study investigated the potential role of nitric oxide (NO) and its interaction with renal sympathetic nerves in modulating the excretory responses to an acute saline volume expansion (VE), of 10% of body weight, in the innervated and denervated kidneys of both lean and obese Zucker rats. This was done using the NO synthase inhibitors NG-nitro-l-arginine methyl ester (l-NAME), 7-nitroindazole and aminoguanidine. In lean rats, cumulative urinary sodium excretion (cuUNaV) after 40 min of VE in the innervated kidney was enhanced by 48% in l-NAME-treated rats compared with that in untreated rats, but this was not the case for the denervated kidney. VE in untreated obese rats raised cuUNaV to a lesser extent than in the untreated lean rats, by 36% and 46% in the denervated and innervated kidneys respectively (both P < 0.001). l-NAME treatment of obese rats increased cuUNaV after VE compared with that in untreated obese rats, by 48% in the denervated kidney and by 136% in the innervated kidney (both P < 0.001). The magnitude of cuUNaV after VE in both kidneys of 7-nitroindazole-treated obese rats was not different from that in untreated obese rats. However, cuUNaV was raised (P < 0.01) by 56% in the innervated, but not the denervated, kidney of aminoguanidine-treated obese rats. These data show that NO is partially involved in mediating the reflex renal responses to VE in Zucker rat strains. NO, possibly generated by endothelial NO synthase, exerts its effects in obese rats through a renal-nerve-independent mechanism, while the effect of NO generated by inducible NO synthase requires intact renal innervation.

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Endothelial dysfunction in renal arcuate arteries of obese Zucker rats: The roles of nitric oxide, endothelium-derived hyperpolarizing factors, and calcium-activated K+ channels

PLoS ONE ◽

10.1371/journal.pone.0183124 ◽

2017 ◽

Vol 12 (8) ◽

pp. e0183124 ◽

Cited By ~ 7

Author(s):

Dandan Yin ◽

Qianchen Wang ◽

Xun Zhou ◽

Ying Li

Keyword(s):

Nitric Oxide ◽

Endothelial Dysfunction ◽

Zucker Rats ◽

K Channels ◽

Obese Zucker Rats

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/5413423 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 5

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.

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

International Journal of Medicine ◽

10.14419/ijm.v2i1.1941 ◽

2014 ◽

Vol 2 (1) ◽

Cited By ~ 1

Author(s):

Priyanka Prathipati ◽

Syed Quadri ◽

Debra Jackson ◽

Keith Jackson

Keyword(s):

Nitric Oxide ◽

Coronary Arteries ◽

Zucker Rats ◽

Obese Zucker Rats

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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

Journal of Sexual Medicine ◽

10.1111/jsm.12526 ◽

2014 ◽

Vol 11 (6) ◽

pp. 1463-1474 ◽

Cited By ~ 9

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

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Increased vascular thromboxane generation impairs dilation of skeletal muscle arterioles of obese Zucker rats with reduced oxygen tension

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00596.2008 ◽

2008 ◽

Vol 295 (4) ◽

pp. H1522-H1528 ◽

Cited By ~ 26

Author(s):

Adam G. Goodwill ◽

Milinda E. James ◽

Jefferson C. Frisbee

Keyword(s):

Nitric Oxide ◽

Skeletal Muscle ◽

Superoxide Dismutase ◽

Arachidonic Acid ◽

Polyethylene Glycol ◽

Nitric Oxide Synthase ◽

Oxidant Stress ◽

Zucker Rats ◽

Obese Zucker Rats ◽

Oxide Synthase

This study determined if altered vascular prostacyclin (PGI2) and/or thromboxane A2 (TxA2) production with reduced Po2 contributes to impaired hypoxic dilation of skeletal muscle resistance arterioles of obese Zucker rats (OZRs) versus lean Zucker rats (LZRs). Mechanical responses were assessed in isolated gracilis muscle arterioles following reductions in Po2 under control conditions and following pharmacological interventions inhibiting arachidonic acid metabolism and nitric oxide synthase and alleviating elevated vascular oxidant stress. The production of arachidonic acid metabolites was assessed using pooled arteries from OZRs and LZRs in response to reduced Po2. Hypoxic dilation, endothelium-dependent in both strains, was attenuated in OZRs versus LZRs. Nitric oxide synthase inhibition had no significant impact on hypoxic dilation in either strain. Cyclooxygenase inhibition dramatically reduced hypoxic dilation in LZRs and abolished responses in OZRs. Treatment of arterioles from OZRs with polyethylene glycol-superoxide dismutase improved hypoxic dilation, and this improvement was entirely cyclooxygenase dependent. Vascular PGI2 production with reduced Po2 was similar between strains, although TxA2 production was increased in OZRs, a difference that was attenuated by treatment of vessels from OZRs with polyethylene glycol-superoxide dismutase. Both blockade of PGH2/TxA2 receptors and inhibition of thromboxane synthase increased hypoxic dilation in OZR arterioles. These results suggest that a contributing mechanism underlying impaired hypoxic dilation of skeletal muscle arterioles of OZRs may be an increased vascular production of TxA2, which competes against the vasodilator influences of PGI2. These results also suggest that the elevated vascular oxidant stress inherent in metabolic syndrome may contribute to the increased vascular TxA2 production and may blunt vascular sensitivity to PGI2.

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