Enalapril prevents impaired nitric oxide synthase-dependent dilatation of cerebral arterioles in diabetic rats.
OBJECTIVE
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.
Trauernicht
Anna K
AK
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, NE, USA.
Sun
Hong
H
Patel
Kaushik P
KP
Mayhan
William G
WG
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D001921:Brain / Q000098:blood supply; D002536:Cerebral Arteries / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017207:Rats, Sprague-Dawley; D014654:Vascular Patency / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D004656:Enalapril; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat