Acetazolamide and enalapril combination offers complete protection from nitric oxide-deficient stroke in stroke-prone spontaneously hypertensive rats.
Chronic oral administration of l -NAME precipitates stroke in stroke-prone spontaneously hypertensive rats (SHRSP). The present study investigated whether acetazolamide (an acidotic agent) given alone or in combination with an angiotensin blocker (enalapril maleate) offers any protection from NO-deficient stroke in SHRSP. We also examined whether protection from NO-deficient stroke involves activation of K(+)channels. Five-week-old SHRSP drank saline (group I), l -NAME (group II), l -NAME+enalapril (group III), l -NAME+acetazolamide (group IV), and l -NAME+enalapril+acetazolamide (group V). Within a few hours following onset of stroke, rats were attached to a blood pressure recorder. In subsequent experiments, to investigate the involvement of K(+)channels, glibenclamide and BaCl(2)(K(+)channel blockers) were included in the drinking solutions that were given to the SHRSP groups receiving l -NAME, acetazolamide and enalapril. Group I of SHRSP did not develop stroke. Group II, III and IV developed stroke in 12+/-2, 29+/-2 and 20+/-2 days, respectively. SHRSP from group V did not develop stroke. However, they died in 70+/-2 days. The glibenclamide and BaCl(2)administration failed to prevent this protection from stroke. In conclusion, concurrent administration of acetazolamide and enalapril prevents onset of NO-deficient stroke in SHRSP. These stroke-protective effects are independent of reductions in mean or systolic blood pressures and do not involve an activation of K(+)channels.
Ahmad
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Department of Pharmacology, Arnold and Marie Schwartz, College of Pharmacy, Long Island University, 75 Dekalb Avenue, Brooklyn, New York, NY 11201, USA.
D000086:Acetazolamide / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D017609:Barium Compounds / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage*; D002712:Chlorides / Q000008:administration & dosage; D004347:Drug Interactions; D004656:Enalapril / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005905:Glyburide / Q000008:administration & dosage; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000503:physiopathology / Q000517:prevention & control*
D000806:Angiotensin-Converting Enzyme Inhibitors; D017609:Barium Compounds; D002257:Carbonic Anhydrase Inhibitors; D002712:Chlorides; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C024986:barium chloride; D009569:Nitric Oxide; D004656:Enalapril; D019001:Nitric Oxide Synthase; D000086:Acetazolamide; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester