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ACETYLCHOLINE‐INDUCED SYSTEMIC VASODILATION RESISTANT TO N G ‐NITRO‐L‐ARGININE IN ANAESTHETIZED RATS
Author(s) -
Kakizoe Eiichi,
Wang DanQiao,
Kobayashi Yuta,
Shimoura Keiko,
Okunishi Hideki
Publication year - 1998
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1998.tb02244.x
Subject(s) - phenylephrine , vasodilation , endocrinology , acetylcholine , medicine , nitric oxide , endothelium derived relaxing factor , nitroarginine , chemistry , basal (medicine) , endogeny , blood pressure , anesthesia , nitric oxide synthase , insulin
SUMMARY 1. The effects of N G ‐nitro‐L‐arginine ( l ‐NNA; 20mg/kg bodyweight (BW), i.v.) and metyrapone (300 mg/kg BW, s.c.) on acetylcholine (ACh)‐induced depressor responses were investigated in anaesthetized rats. 2. Acetylcholine (0.05,0.5,5 μg/kg BW, i.v.) dose‐dependently evoked a sharp fall in mean blood pressure (BP) followed by a slow recovery under control conditions. 3. Basal BP level was elevated when rats were treated with l ‐NNA, indicating endogenous nitric oxide (NO) participated in BP regulation. However, pretreatment with l ‐NNA did not attenuate but rather augmented the ACh‐induced maximum vasodilation. In contrast, the time for recovery of mean BP to the pre‐ACh administration level was shortened by l ‐NNA. These observations suggested that ACh‐induced vasodilation consisted of two phases: a sharp and transient fall (phase 1) that was resistant to l ‐NNA followed by a longer depressor response (phase 2) that was suppressed by l ‐NNA. 4. To examine whether augmentation of phase 1 by l ‐NNA resulted from the elevation of basal BP, an appropriate dose of phenylephrine was infused to obtain similar BP elevation. Phenylephrine infusion augmented the phase 1 in a similar manner to l ‐NNA pretreatment but showed little effect on phase 2, supporting the selective inhibition of phase 2 by l ‐NNA. 5. The s.c. pretreatment with metyrapone for 3 days failed to attenuate phase 1. Thus, the involvement of endothelium‐derived hyperpolarizing factor that could be formed by a metyrapone‐sensitive oxidase in phase 1 was unlikely. 6. These results suggest that some factor(s), which is not inhibitable by l ‐NNA or metyrapone, may induce the phase 1 depressor response to ACh while NO is responsible for the phase 2 response. The mechanism inducing the phase 1 response remains to be identified.