RGD Reference Report - Role of myocardial neuronal nitric oxide synthase-derived nitric oxide in beta-adrenergic hyporesponsiveness after myocardial infarction-induced heart failure in rat. - Rat Genome Database

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Role of myocardial neuronal nitric oxide synthase-derived nitric oxide in beta-adrenergic hyporesponsiveness after myocardial infarction-induced heart failure in rat.

Authors: Bendall, JK  Damy, T  Ratajczak, P  Loyer, X  Monceau, V  Marty, I  Milliez, P  Robidel, E  Marotte, F  Samuel, JL  Heymes, C 
Citation: Bendall JK, etal., Circulation. 2004 Oct 19;110(16):2368-75. Epub 2004 Oct 4.
RGD ID: 1581144
Pubmed: PMID:15466641   (View Abstract at PubMed)
DOI: DOI:10.1161/01.CIR.0000145160.04084.AC   (Journal Full-text)

BACKGROUND: An emerging concept is that a neuronal isoform of nitric oxide synthase (NOS1) may regulate myocardial contractility. However, a role for NOS1-derived nitric oxide (NO) in heart failure (HF) has not been defined. METHODS AND RESULTS: Using a model of myocardial infarction-induced HF, we demonstrated that cardiac NOS1 expression and activity increased in HF rats (P<0.05 and P<0.001 versus shams, respectively). This was associated with translocation of NOS1 from the ryanodine receptor to the sarcolemma through interactions with caveolin-3 in HF hearts. With ex vivo and in vivo pressure-volume analysis, cardiac NOS1-derived NO was found to be negatively inotropic in shams but not HF hearts. Ventricular elastance (E(es)) was significantly reduced in HF rats (P<0.05), and tau, the time constant of left ventricular relaxation, was prolonged (both P<0.05). Acute NOS1 inhibition significantly increased E(es) by 33+/-3% and tau by 17+/-2% (P<0.05) in shams, although these effects were significantly attenuated in HF hearts. beta-Adrenergic stimulation induced a marked increase in systolic performance in sham hearts, with the responses being significantly blunted in HF hearts. E(es) increased by 163+/-42% (P<0.01) in sham hearts and 56+/-9% in HF hearts, and LV +dP/dt increased by 97+/-9% (P<0.01) in shams and 37+/-7% (P<0.05) in the HF group. Interestingly, preferential NOS1 inhibition enhanced the blunted responses of LV +dP/dt and E(es) to beta-adrenergic stimulation in HF rats but had no effect in shams. CONCLUSIONS: These results provide the first evidence that increased NOS1-derived NO production may play a role in the autocrine regulation of myocardial contractility in HF.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
congestive heart failure  ISONos1 (Rattus norvegicus)1581144; 1581144 RGD 
congestive heart failure  IEP 1581144 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nos1  (nitric oxide synthase 1)

Genes (Mus musculus)
Nos1  (nitric oxide synthase 1, neuronal)

Genes (Homo sapiens)
NOS1  (nitric oxide synthase 1)


Additional Information