Exercise Training Normalizes Impaired NOS-dependent Responses of Cerebral Arterioles in Type 1 Diabetic Rats

Overview

Journal Am J Physiol Heart Circ Physiol

Publisher American Physiological Society

Specialties Cardiology & Vascular Diseases
Physiology

Date 2010 Dec 21

PMID 21169403

Citations 19

Authors

William G Mayhan

Denise M Arrick

Kaushik P Patel

Hong Sun

Affiliations

Soon will be listed here.

Abstract

Our goal was to examine whether exercise training (ExT) could normalize impaired nitric oxide synthase (NOS)-dependent dilation of cerebral (pial) arterioles during type 1 diabetes (T1D). We measured the in vivo diameter of pial arterioles in sedentary and exercised nondiabetic and diabetic rats in response to an endothelial NOS (eNOS)-dependent (ADP), an neuronal NOS (nNOS)-dependent [N-methyl-D-aspartate (NMDA)], and a NOS-independent (nitroglycerin) agonist. In addition, we measured superoxide anion levels in brain tissue under basal conditions in sedentary and exercised nondiabetic and diabetic rats. Furthermore, we used Western blot analysis to determine eNOS and nNOS protein levels in cerebral vessels/brain tissue in sedentary and exercised nondiabetic and diabetic rats. We found that ADP and NMDA produced a dilation of pial arterioles that was similar in sedentary and exercised nondiabetic rats. In contrast, ADP and NMDA produced only minimal vasodilation in sedentary diabetic rats. ExT restored impaired ADP- and NMDA-induced vasodilation observed in diabetic rats to that observed in nondiabetics. Nitroglycerin produced a dilation of pial arterioles that was similar in sedentary and exercised nondiabetic and diabetic rats. Superoxide levels in cortex tissue were similar in sedentary and exercised nondiabetic rats, were increased in sedentary diabetic rats, and were normalized by ExT in diabetic rats. Finally, we found that eNOS protein was increased in diabetic rats and further increased by ExT and that nNOS protein was not influenced by T1D but was increased by ExT. We conclude that ExT can alleviate impaired eNOS- and nNOS-dependent responses of pial arterioles during T1D.

Citing Articles

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A cannabinoid type 2 (CB2) receptor agonist augments NOS-dependent responses of cerebral arterioles during type 1 diabetes.

Van Hove L, Kim K, Arrick D, Mayhan W Microvasc Res. 2020; 133:104077.

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References

Armstead W . NOC/oFQ PKC-dependent superoxide generation contributes to hypoxic-ischemic impairment of NMDA cerebrovasodilation. Am J Physiol Heart Circ Physiol. 2000; 279(6):H2678-84. DOI: 10.1152/ajpheart.2000.279.6.H2678. View

Arrick D, Sharpe G, Sun H, Mayhan W . nNOS-dependent reactivity of cerebral arterioles in Type 1 diabetes. Brain Res. 2007; 1184:365-71. PMC: 2174607. DOI: 10.1016/j.brainres.2007.10.004. View

Zheng H, Li Y, Cornish K, Zucker I, Patel K . Exercise training improves endogenous nitric oxide mechanisms within the paraventricular nucleus in rats with heart failure. Am J Physiol Heart Circ Physiol. 2005; 288(5):H2332-41. DOI: 10.1152/ajpheart.00473.2004. View

Sun D, Huang A, Koller A, Kaley G . Enhanced NO-mediated dilations in skeletal muscle arterioles of chronically exercised rats. Microvasc Res. 2002; 64(3):491-6. DOI: 10.1006/mvre.2002.2450. View

Oltman C, Parker J, Laughlin M . Endothelium-dependent vasodilation of proximal coronary arteries from exercise-trained pigs. J Appl Physiol (1985). 1995; 79(1):33-40. DOI: 10.1152/jappl.1995.79.1.33. View

Arvanitakis Z, Wilson R, Bienias J, Evans D, Bennett D . Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 2004; 61(5):661-6. DOI: 10.1001/archneur.61.5.661. View

Ozbek E, Tasci A, Ilbey Y, Simsek A, Somay A, Metin G . The effect of regular exercise on penile nitric oxide synthase expression in rats. Int J Androl. 2009; 33(4):623-8. DOI: 10.1111/j.1365-2605.2009.00993.x. View

Faraci F, Heistad D . Role of ATP-sensitive potassium channels in the basilar artery. Am J Physiol. 1993; 264(1 Pt 2):H8-13. DOI: 10.1152/ajpheart.1993.264.1.H8. View

You J, Johnson T, Marrelli S, Mombouli J, Bryan Jr R . P2u receptor-mediated release of endothelium-derived relaxing factor/nitric oxide and endothelium-derived hyperpolarizing factor from cerebrovascular endothelium in rats. Stroke. 1999; 30(5):1125-33. DOI: 10.1161/01.str.30.5.1125. View

10.

Powers S, Ji L, Leeuwenburgh C . Exercise training-induced alterations in skeletal muscle antioxidant capacity: a brief review. Med Sci Sports Exerc. 1999; 31(7):987-97. DOI: 10.1097/00005768-199907000-00011. View

11.

Roghani M, Baluchnejadmojarad T . Mechanisms underlying vascular effect of chronic resveratrol in streptozotocin-diabetic rats. Phytother Res. 2009; 24 Suppl 2:S148-54. DOI: 10.1002/ptr.3032. View

12.

Harris M, Mitchell B, Sood S, Webb R, Venema R . Increased nitric oxide synthase activity and Hsp90 association in skeletal muscle following chronic exercise. Eur J Appl Physiol. 2008; 104(5):795-802. PMC: 3884582. DOI: 10.1007/s00421-008-0833-4. View

13.

Mayhan W . Endothelium-dependent responses of cerebral arterioles to adenosine 5'-diphosphate. J Vasc Res. 1992; 29(5):353-8. DOI: 10.1159/000158951. View

14.

Xiang L, Naik J, Hester R . Exercise-induced increase in skeletal muscle vasodilatory responses in obese Zucker rats. Am J Physiol Regul Integr Comp Physiol. 2004; 288(4):R987-91. DOI: 10.1152/ajpregu.00702.2004. View

15.

Maiorana A, ODriscoll G, Cheetham C, Dembo L, Stanton K, Goodman C . The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes. J Am Coll Cardiol. 2001; 38(3):860-6. DOI: 10.1016/s0735-1097(01)01439-5. View

16.

Chen Y, Collins H, DiCarlo S . Daily exercise enhances acetylcholine-induced dilation in mesenteric and hindlimb vasculature of hypertensive rats. Clin Exp Hypertens. 1999; 21(4):353-76. DOI: 10.3109/10641969909068670. View

17.

Sun H, Zheng H, Molacek E, Fang Q, Patel K, Mayhan W . Role of NAD(P)H oxidase in alcohol-induced impairment of endothelial nitric oxide synthase-dependent dilation of cerebral arterioles. Stroke. 2005; 37(2):495-500. DOI: 10.1161/01.STR.0000199033.06678.c3. View

18.

Yu W, Juang S, CHIN W, CHI T, Chang C, Cheng J . Insulin restores neuronal nitric oxide synthase expression in streptozotocin-induced diabetic rats. Life Sci. 2001; 68(6):625-34. DOI: 10.1016/s0024-3205(00)00967-x. View

19.

Sun D, Huang A, Koller A, Kaley G . Short-term daily exercise activity enhances endothelial NO synthesis in skeletal muscle arterioles of rats. J Appl Physiol (1985). 1994; 76(5):2241-7. DOI: 10.1152/jappl.1994.76.5.2241. View

20.

Faraci F, Breese K, Heistad D . Responses of cerebral arterioles to kainate. Stroke. 1994; 25(10):2080-3; discussion 2084. DOI: 10.1161/01.str.25.10.2080. View