This Article Full Text Full Text (PDF) All Versions of this Article: 34/11/2698    most recent 01.STR.0000092121.62649.DCv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Trauernicht, A. K. Articles by Mayhan, W. G. Search for Related Content PubMed PubMed Citation Articles by Trauernicht, A. K. Articles by Mayhan, W. G. Related Collections ACE/Angiotension receptors Type 1 diabetes Brain Circulation and Metabolism Endothelium/vascular type/nitric oxide

(Stroke. 2003;34:2698.)
© 2003 American Heart Association, Inc.

Original Contributions

Enalapril Prevents Impaired Nitric Oxide Synthase–Dependent Dilatation of Cerebral Arterioles in Diabetic Rats

From the Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha.

Correspondence to Dr William G. Mayhan, Department of Physiology and Biophysics, 984575 Nebraska Medical Center, Omaha, NE 68198-4575. E-mail wgmayhan{at}unmc.edu

Background and Purpose— Our goal was to identify the effects of chronic treatment with enalapril on cerebrovascular dysfunction and endothelial nitric oxide synthase (eNOS) protein in diabetic rats.

Methods— Rats were assigned to 1 of 4 groups: nondiabetic, diabetic, nondiabetic/enalapril-treated, and diabetic/enalapril-treated groups. Rats assigned to the nondiabetic groups were injected with vehicle (sodium citrate buffer), and rats assigned to the diabetic groups were injected with streptozotocin (50 mg/kg IP). Enalapril (10 mg/kg per day) was administered in the drinking water and coincided with the injection of vehicle or streptozotocin. Two to 3 months later, we examined responses of pial arterioles to nitric oxide synthase (NOS)–dependent agonists (acetylcholine and ADP) and a NOS-independent agonist (nitroglycerin). After these functional studies, we harvested cerebral microvessels for Western blot analysis of eNOS protein.

Results— We found that acetylcholine- and ADP-induced dilatation of pial arterioles was impaired in diabetic compared with nondiabetic rats. In addition, while enalapril did not alter responses in nondiabetic rats, enalapril prevented diabetes-induced impairment of NOS-dependent vasodilatation. Furthermore, eNOS protein was higher in diabetic than in nondiabetic rats, and enalapril did not produce a further increase in eNOS protein in enalapril-treated diabetic rats compared with untreated diabetic rats.

Conclusions— These results suggest that enalapril prevents cerebrovascular dysfunction in diabetic rats. We speculate that the protective role of enalapril may be independent of an alteration in eNOS protein in cerebral microvessels.

Key Words: acetylcholine • adenosine • angiotensin converting enzyme inhibitors • brain • nitric oxide • nitroglycerin • stroke • rats

This article has been cited by other articles:

				N. Toda, K. Ayajiki, and T. Okamura Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances Pharmacol. Rev., March 1, 2009; 61(1): 62 - 97. [Abstract] [Full Text] [PDF]

				R. Zhang, Y.-G. Bai, L.-J. Lin, J.-X. Bao, Y.-Y. Zhang, H. Tang, J.-H. Cheng, G.-L. Jia, X.-L. Ren, and J. Ma Blockade of AT1 receptor partially restores vasoreactivity, NOS expression, and superoxide levels in cerebral and carotid arteries of hindlimb unweighting rats J Appl Physiol, January 1, 2009; 106(1): 251 - 258. [Abstract] [Full Text] [PDF]

				D. Last, D. C. Alsop, A. M. Abduljalil, R. P. Marquis, C. de Bazelaire, K. Hu, J. Cavallerano, and V. Novak Global and Regional Effects of Type 2 Diabetes on Brain Tissue Volumes and Cerebral Vasoreactivity Diabetes Care, May 1, 2007; 30(5): 1193 - 1199. [Abstract] [Full Text] [PDF]

				N. Toda, K. Ayajiki, and T. Okamura Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation Pharmacol. Rev., March 1, 2007; 59(1): 54 - 87. [Abstract] [Full Text] [PDF]

				V. Novak, D. Last, D. C. Alsop, A. M. Abduljalil, K. Hu, L. Lepicovsky, J. Cavallerano, and L. A. Lipsitz Cerebral Blood Flow Velocity and Periventricular White Matter Hyperintensities in Type 2 Diabetes Diabetes Care, July 1, 2006; 29(7): 1529 - 1534. [Abstract] [Full Text] [PDF]

				T. Fujiki, H. Shimokawa, K. Morikawa, H. Kubota, M. Hatanaka, M.A. H. Talukder, T. Matoba, A. Takeshita, and K. Sunagawa Endothelium-Derived Hydrogen Peroxide Accounts for the Enhancing Effect of an Angiotensin-Converting Enzyme Inhibitor on Endothelium-Derived Hyperpolarizing Factor-Mediated Responses in Mice Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 766 - 771. [Abstract] [Full Text] [PDF]

				W. G. Mayhan, H. Sun, J. F. Mayhan, and K. P. Patel Influence of exercise on dilatation of the basilar artery during diabetes mellitus J Appl Physiol, May 1, 2004; 96(5): 1730 - 1737. [Abstract] [Full Text] [PDF]