Streptozotocin-induced diabetes enhances protective effects of enalapril on nitric oxide-deficient stroke in stroke-prone rats.
Recently, we have shown that chronic administration of N-Nitro-L-Arginine Methyl Ester (L-NAME, an inhibitor of nitric oxide synthase) precipitates stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Enalapril maleate, an angiotensin converting enzyme inhibitor was shown to delay the onset of such stroke. In the present study, five groups of 4-week-old SHRSP were used. Three groups of SHRSP were made diabetic using streptozotocin (100 mg/kg i.p.). One week later, the SHRSP from groups I (non-diabetic) and III (diabetic) chronically received L-NAME (0.5 g/L) in saline as drinking water. Two SHRSP groups, II (non-diabetic) and IV (diabetic) received L-NAME (0.5 g/L) and enalapril maleate (20 mg/L) in saline as drinking water. Control SHRSP (group C; diabetic) received only saline to drink. SHRSP groups I and III developed stroke in 10+/-2 and 11+/-2 days, respectively. The average stroke-free period in groups II and IV was 19+/-2 and 28+/-2 days, respectively. Protective effect of streptozotocin-induced diabetes disappeared when SHRSP drinking L-NAME and enalapril, concurrently received subcutaneous injections of insulin (2 units daily per 100 g rat). Present data suggest that experimental diabetes delays the onset of L-NAME-induced stroke in SHRSP only in the absence of angiotensin converting enzyme activity. In addition, diabetes-induced enhancement of stroke-protective effect of enalapril appears to be independent of reduction in mean and systolic blood pressures.
Ahmad
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Department of Pharmacology, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York 11201, USA. AHMAS@aol.com
Eisa
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AK
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002561:Cerebrovascular Disorders / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004656:Enalapril / Q000494:pharmacology*; D019332:Endothelin-1 / Q000502:physiology; D006973:Hypertension / Q000150:complications*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D013311:Streptozocin; D015430:Weight Gain
D000806:Angiotensin-Converting Enzyme Inhibitors; D019332:Endothelin-1; D009569:Nitric Oxide; D013311:Streptozocin; D004656:Enalapril; D019331:NG-Nitroarginine Methyl Ester