Anorectic activity of NG-nitro-L-arginine, an inhibitor of brain nitric oxide synthase, in obese Zucker rats

1993 ◽  
Vol 230 (1) ◽  
pp. 125-128 ◽  
Author(s):  
Francesco Squadrito ◽  
Gioacchino Calapai ◽  
Domenico Cucinotta ◽  
Domenica Altavilla ◽  
Basilia Zingarelli ◽  
...  
2008 ◽  
Vol 295 (4) ◽  
pp. H1522-H1528 ◽  
Author(s):  
Adam G. Goodwill ◽  
Milinda E. James ◽  
Jefferson C. Frisbee

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.


1996 ◽  
Vol 209 (2) ◽  
pp. 137-139 ◽  
Author(s):  
John E. Morley ◽  
Michael B. Mattammal

2007 ◽  
Vol 4 (3) ◽  
pp. 214-229 ◽  
Author(s):  
Shahla Riazi ◽  
Veerendra K. Madala-Halagappa ◽  
Ana Paula Dantas ◽  
Xinqun Hu ◽  
Carolyn A. Ecelbarger

1994 ◽  
Vol 304 (3) ◽  
pp. 683-686 ◽  
Author(s):  
C Harteneck ◽  
P Klatt ◽  
K Schmidt ◽  
B Mayer

Rat brain nitric oxide synthase was expressed to a high level in baculovirus-infected insect cells and purified to apparent homogeneity by affinity chromatography. The enzyme had a specific activity of approximately 1 mumol of citrulline.min-1.mg of protein-1 and contained 0.93, 0.45, 0.18 and 0.23 mol of haem, (6R)-5,6,7,8-tetrahydro-L-biopterin (H4biopterin), FAD and FMN per mol of subunit respectively.


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