Effect of experimental diabetes on the protection by angiotensin blockers on nitric oxide deficient stroke in stroke-prone spontaneously hypertensive 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). Angiotensin receptor antagonist (L-158,809) 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.). SHRSP from groups I (non-diabetic) and III (diabetic) chronically received L-NAME(0.5 g/L) and L-158,809 (20 mg/L) in saline to drink. Diabetic SHRSP (group C) received only saline to drink. SHRSP groups I and III developed stroke in 10+/-2 and 11+/-2 days. Average stroke-free period in groups II and IV was 18+/-2 and 29+/-2 days, respectively. Protective effect of streptozotocin-induced diabetes disappeared when SHRSP drinking L-NAME and L-158,809, also received subcutaneous injections of insulin. Present data suggest that experimental diabetes delays the onset of L-NAME-induced stroke in SHRSP and this protection is seen in the absence of renin-angiotensin system.
Raje
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Department of Pharmacology, Toxicology and Medicinal Chemistry, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University Brooklyn, New York, USA.
Ahmad
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D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002561:Cerebrovascular Disorders / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011918:Rats, Inbred SHR; D013311:Streptozocin; D013777:Tetrazoles / Q000494:pharmacology
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007328:Insulin; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D013311:Streptozocin; C070967:L 158809; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester