Effects of chronic and acute aminoguanidine treatment on tail artery vasomotion in ageing rats.
1. This study was designed to evaluate the effects of aminoguanidine, a selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), on the reactivity and intracellular calcium ([Ca(2+)](i)) mobilization induced by noradrenaline in the perfused tail artery from aged WAG/Rij rats. Global mean internal diameter was 350+/-15 microns and wall thickness 161+/-3 microns. The influence of the endothelium on these responses was also analysed. The intracellular dye fura-2 for [Ca(2+)](i) measurements was used. 2. Noradrenaline-induced vasoconstriction decreased progressively from 3 to 20 and 30 months. Removal of the endothelium attenuated vasoconstriction in 20 and 30 month-old rats (P<0.05) but not in young rats. 3. Chronic administration of aminoguanidine (50 mg kg(-1) day(-1), p.o.) to WAG/Rij rats from 20 to 30 months enhanced (P<0. 01) the [Ca(2+)](i)-sensitivity of noradrenaline-induced vasoconstriction. 4. Aminoguanidine (300 microM) in vitro significantly shifted the concentration-vasoconstriction curve to noradrenaline to the left (P<0.01) in denuded vessels from both 20 and 30 month-old rats. The acute inhibitory effect of aminoguanidine was also observed after chronic aminoguanidine treatment. Aminoguanidine failed to modify vasoconstriction in the presence of the endothelium. 5. Acute aminoguanidine (300 microM) treatment did not modify vasoconstriction induced by noradrenaline in young rats. 6. Quantification of iNOS mRNA expression in tail arteries from 3 and 20 month-old WAG/Rij rats showed that expression was enhanced (x2.1, P<0.01) with age. 7. These results suggest that an inflammatory process develops in the media of the rat tail artery with age and that the subsequent increase in non-endothelial iNOS activity attenuates noradrenaline-induced vasoconstriction.
Tabernero
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Laboratoire de Pharmacologie Cardiovasculaire, UPRES EA 3116. Faculté de Pharmacie, UHP-Nancy I, 5 rue Albert Lebrun, 54001 Nancy Cedex, France.
Nadaud
S
S
Corman
B
B
Atkinson
J
J
Capdeville-Atkinson
C
C
D000367:Age Factors; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009638:Norepinephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013623:Tail / Q000098:blood supply* / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006146:Guanidines; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine