title: Different vasoactive effects of chronic endothelial and neuronal NO-synthase inhibition in young Wistar rats.
abstract: While the unequivocal pattern of endothelial nitric oxide synthase (eNOS) inhibition in cardiovascular control is recognized, the role of NO produced by neuronal NOS (nNOS) remains unclear. The aim of this study was to compare the effects of chronic treatment with 7-nitroindazole (7-NI, nNOS inhibitor) and N(G)-nitro-L-arginine methylester (L-NAME, general and predominantly eNOS inhibitor) on cardiovascular system of young normotensive rats. Wistar rats (4 weeks old) were used: controls and rats administered either 7-NI (10 mg/kg bw/day) or L-NAME (50 mg/kg bw/day) in drinking water for 6 weeks. The systolic blood pressure (sBP) was measured by plethysmographic method, and the vasoactivity of isolated arteries was recorded. 7-NI-treatment did not affect sBP; however, the sBP was increased after L-NAME-treatment. L-NAME inhibited acetylcholine-induced relaxation of thoracic aorta (TA), whereas it remained unchanged after 7-NI-treatment. The response of TA to sodium nitroprusside was increased in both experimental groups. The expression of eNOS and nNOS in TA was unchanged in both experimental groups, whereas the activity of NOS was decreased in L-NAME-treated group. Noradrenaline- and angiotensin II-induced contractions of TA were reduced in L-NAME-treated group; however, the contractions remained unchanged in 7-NI-treated group. In all groups, the endogenous angiotensin II participated in adrenergic contraction of TA; this contribution was significantly increased in L-NAME-treated group. Neurogenic contractions in mesenteric artery (MA) remained unchanged after 7-NI-treatment, but increased after L-NAME-treatment. Results show that NO deficiency induced by administration of 7-NI and L-NAME had different cardiovascular effects: eNOS and nNOS triggered distinct signaling pathways in young normotensive rats.
authors: Institute of Normal and Pathological Physiology, Centre of Excellence for Examination of Regulatory Role of Nitric Oxide in Civilization Diseases, Slovak Academy of Sciences, Bratislava, Slovak Republic, sona.cacanyiova@savba.sk.
authors: Sona
authors: S
authors: Cacanyiova
authors: Andrea
authors: A
authors: Berenyiova
authors: Magdalena
authors: M
authors: Malekova
authors: Frantisek
authors: F
authors: Kristek
authors: Ima
authors: I
authors: Dovinova
authors: Peter
authors: P
authors: Krenek
authors: Lenka
authors: L
authors: Pivackova
authors: Ivana
authors: I
authors: Pifkova
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors* / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors* / Q000235:genetics; D009599:Nitroprusside / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester