期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 32, 期 10, 页码 1795-1804出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1006/jmcc.2000.1214
关键词
nitric oxide; autonomic nervous system; acetylcholine; heart rate; guinea pig
The role of nitric oxide (NO) in the vagal modulation of heart rate (HR) is controversial. We tested the hypothesis that NO acts via a pre-synaptic, guanylyl cyclase (GC) dependent pathway. The effects of inhibiting NO synthase (NOS) and GC were evaluated in isolated atrial/right vagal nerve preparations From adult (550-750 g) and young (150-250 g) female guinea pigs. Levels of NOS protein were quantified in right atria using Western blotting and densitometry. The non-specific NOS inhibitor N-omega -nitro-L-arginine (L-NA, 100 muM, n = 5) significantly reduced the negative chronotropic response to vagal nerve stimulation (VNS) at 3 and 5 Hz in the adult guinea pig. This effect was reversed with 1 mM L-arginine. Similar results were observed with the specific neuronal NOS inhibitor vinyl-N5-(1-imino-3-butenyl)-L-ornithine (L-VNIO, 100 muM, n = 7). Inhibition of GC with 1H-(1,2,4)-oxadiazolo-(4,3-a)-quinoxalin-1-one (ODQ, 10 muM, n = 7) also significantly reduced the negative chronotropic response to VNS at 3 and 5 Hz in adult guinea pigs. Neither L-NA (n = 6), L-VNIO (n = 5) nor ODQ (n = 6) changed the HR response to cumulative doses of carbamylcholine in adult guinea pig atria suggesting that the action of NO is pre-synaptic. The IIR response to VNS was unaffected by L-NA (n = 7) or ODQ (n = 7) in young guinea pigs and Western blot analysis showed significantly lower levels of nNOS protein in right atria from young animals. These results suggest a pre-synaptic NO-cGMP pathway modulates cardiac cholinergic transmission, although this may depend on the developmental stage of the guinea pig. (C) 2000 Academic Press.
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