scholarly journals Tetrahydrobiopterin rescues impaired responses of cerebral resistance arterioles during type 1 diabetes

2016 ◽  
Vol 14 (1) ◽  
pp. 33-39 ◽  
Author(s):  
William G Mayhan ◽  
Denise M Arrick
Keyword(s):  
Nitric Oxide ◽  
Type 1 Diabetes ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Therapeutic Potential ◽  
Diabetic Rats ◽  
Cerebral Arterioles ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Our goal was to test the hypothesis that administration of tetrahydrobiopterin (BH4) would improve impaired endothelial nitric oxide synthase–dependent dilation of cerebral arterioles during type 1 diabetes. In addition, we examined the influence of BH4 on levels of superoxide in brain tissue. In vivo diameter of cerebral arterioles in nondiabetic and diabetic rats was measured in response to endothelial nitric oxide synthase–dependent agonists (acetylcholine and adenosine 5′-diphosphate) and an endothelial nitric oxide synthase–independent agonist (nitroglycerine) before and during application of BH4 (1.0 µM). We also measured levels of superoxide from cortex tissue in nondiabetic and diabetic rats under basal states and during BH4. Acetylcholine and adenosine 5′-diphosphate dilated cerebral arterioles in nondiabetic rats, but this vasodilation was significantly impaired in diabetic rats. In contrast, nitroglycerine produced similar vasodilation in nondiabetic and diabetic rats. Application of BH4 did not enhance vasodilation in nondiabetic rats but improved impaired cerebral vasodilation in diabetic rats. Basal superoxide levels were increased in cortex tissue from diabetic rats, and BH4 reduced these levels to that found in nondiabetic rats. Thus, BH4 is an important mediator of endothelial nitric oxide synthase–dependent responses of cerebral arterioles in diabetes and may have therapeutic potential for the treatment of cerebral vascular disease.

Proinsulin C-peptide abrogates type-1 diabetes-induced increase of renal endothelial nitric oxide synthase in rats

2008 ◽  
Vol 24 (4) ◽  
pp. 331-338 ◽  
Author(s):  
Akihiro Kamikawa ◽  
Tatsuya Ishii ◽  
Kohei Shimada ◽  
Kennedy Makondo ◽  
Osamu Inanami ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Type 1 Diabetes ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
C Peptide ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Coinduction of Endothelial Nitric Oxide Synthase and Arginine Recycling Enzymes in Aorta of Diabetic Rats

Nitric Oxide ◽  
2001 ◽  
Vol 5 (3) ◽  
pp. 252-260 ◽  
Author(s):  
Seiichi Oyadomari ◽  
Tomomi Gotoh ◽  
Kazumasa Aoyagi ◽  
Eiichi Araki ◽  
Motoaki Shichiri ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Diabetic Rats ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

scholarly journals The Key Role of Caveolin-1 in Estrogen-Mediated Regulation of Endothelial Nitric Oxide Synthase Function in Cerebral Arterioles In vivo

2001 ◽  
Vol 21 (8) ◽  
pp. 907-913 ◽  
Author(s):  
Hao-Liang Xu ◽  
Elena Galea ◽  
Roberto A. Santizo ◽  
Verna L. Baughman ◽  
Dale A. Pelligrino
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Functional Activity ◽  
Endothelial Nitric Oxide Synthase ◽  
Down Regulation ◽  
Caveolin 1 ◽  
Cerebral Arterioles ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

The marked impairment in cerebrovascular endothelial nitric oxide synthase (eNOS) function that develops after ovariectomy may relate to the observation that the abundance of cerebral vascular eNOS and its endogenous inhibitor, caveolin-1, vary in opposite directions with chronic changes in estrogen status. The authors endeavored, therefore, to establish a link between these correlative findings by independently manipulating, in ovariectomized female rats, eNOS and caveolin-1 expression, while monitoring agonist (acetylcholine)-stimulated eNOS functional activity. In the current study, the authors showed that individually neither the up-regulation of eNOS (through simvastatin treatment), nor the down-regulation of caveolin-1 (through antisense oligonucleotide administration) is capable of restoring eNOS function in pial arterioles in vivo in these estrogen-depleted rats. Only when eNOS up-regulation and caveolin-1 down-regulation are combined is activity normalized. These results establish a mechanistic link between the estrogen-associated divergent changes in the abundance of caveolin-1 and eNOS protein and eNOS functional activity in cerebral arterioles.

Beneficial effect of heme oxygenase-1 expression on myocardial ischemia-reperfusion involves an increase in adiponectin in mildly diabetic rats

2007 ◽  
Vol 293 (6) ◽  
pp. H3532-H3541 ◽  
Author(s):  
Antonio L'Abbate ◽  
Danilo Neglia ◽  
Cecilia Vecoli ◽  
Michela Novelli ◽  
Virginia Ottaviano ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Heme Oxygenase ◽  
Inducible Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Perfusion Pressure ◽  
Diabetic Rats ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Inducible Nitric Oxide

Transient reduction in coronary perfusion pressure in the isolated mouse heart increases microvascular resistance (paradoxical vasoconstriction) by an endothelium-mediated mechanism. To assess the presence and extent of paradoxical vasoconstriction in hearts from normal and diabetic rats and to determine whether increased heme oxygenase (HO)-1 expression and HO activity, using cobalt protoporphyrin (CoPP), attenuates coronary microvascular response, male Wistar rats were rendered diabetic with nicotinamide/streptozotocin for 2 wk and either CoPP or vehicle was administered by intraperitoneal injection weekly for 3 wk (0.5 mg/100 g body wt). The isolated beating nonworking heart was submitted to transient low perfusion pressure (20 mmHg), and coronary resistance (CR) was measured. During low perfusion pressure, CR increased and was associated with increased lactate release. In diabetic rats, CR was higher, HO-1 expression and endothelial nitric oxide synthase were downregulated, and inducible nitric oxide synthase and O2− were upregulated. After 3 wk of CoPP treatment, HO activity was significantly increased in the heart. Upregulation of HO-1 expression and HO activity by CoPP resulted in the abolition of paradoxical vasoconstriction and a reduction in oxidative ischemic damage. In addition, there was a marked increase in serum adiponectin. Elevated HO-1 expression was associated with increased expression of cardiac endothelial nitric oxide synthase, B-cell leukemia/lymphoma extra long, and phospho activator protein kinase levels and decreased levels of inducible nitric oxide synthase and malondialdehyde. These results suggest a critical role for HO-1 in microvascular tone control and myocardial protection during ischemia in both normal and mildly diabetic rats through the modulation of constitutive and inducible nitric oxide synthase expression and activity, and an increase in serum adiponectin.

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