Abstract:
:Cardiovascular aging is associated with decreased endothelial vasoreactivity and prolonged diastolic relaxation. As diminished NO signaling contributes to age-associated endothelial dysfunction, we tested the hypothesis that impaired NO signaling or bioactivity also contributes to slowed ventricular relaxation with age. Accordingly, we measured myocardial NO synthase (NOS) enzyme activity, protein abundance, and cGMP production in old (22 to 25 months) and young adult (4 to 7 months) male Wistar rats. Both NOS3 protein abundance and calcium-dependent NOS activity were elevated in old compared with young adult hearts (7.2+/-1.1 versus 4.2+/-0.6 pmol/mg protein, respectively, P=0.03). However, NOS activity and protein abundance were similar in isolated myocytes, indicating that endothelial NOS likely explains the age difference. Cardiac effluent cGMP (enzyme immunoassay) was 4.8-fold higher (1794+/-373 fmol/min per mg heart tissue) in older versus younger hearts (P=0.003). To assess NO pathway responsiveness, we administered the NOS substrate l-arginine (100 micrometer) to isolated perfused rat hearts. Baseline isovolumic relaxation (tau) was prolonged in old (42.9+/-2.5 ms, n=16) versus young hearts (36.0+/-1.9 ms, n=11, P=0.03). l-Arginine decreased tau (P<0.001) and left ventricular end-diastolic pressure in both old and young hearts. Supporting an NO/cGMP-mediating mechanism, the NO donor sodium nitroprusside reduced tau (maximal effect, -14+/-2%, n=5, P<0.001), and this lusitropic effect was attenuated by the soluble guanylyl cyclase inhibitor 1H:-[1,2,4]oxadiazolo-[4,3,-a]quinoxalin-1-one (n=7, P<0.001). Thus, the NO-cGMP pathway is upregulated in the endothelial cells of aged hearts. l-Arginine, the NOS precursor, enhances ventricular relaxation in old and young hearts, indicating that the NOS pathway may be exploited to modulate diastolic function in aged myocardium.
journal_name
Circ Resjournal_title
Circulation researchauthors
Zieman SJ,Gerstenblith G,Lakatta EG,Rosas GO,Vandegaer K,Ricker KM,Hare JMdoi
10.1161/01.res.88.1.97subject
Has Abstractpub_date
2001-01-19 00:00:00pages
97-102issue
1eissn
0009-7330issn
1524-4571journal_volume
88pub_type
杂志文章abstract::The goal of this study was to test the hypothesis that the cardioprotective effects of the late phase of ischemic preconditioning (PC) can be mimicked by treatment with NO donors. In phase I (studies of myocardial stunning), conscious rabbits underwent a sequence of six 4-minute coronary occlusion/4-minute reperfusion...
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更新日期:2005-11-11 00:00:00
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更新日期:2000-06-09 00:00:00
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更新日期:2002-08-09 00:00:00
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pub_type: 杂志文章
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更新日期:1996-10-01 00:00:00
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更新日期:2011-11-11 00:00:00
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更新日期:1999-05-14 00:00:00
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更新日期:2013-06-07 00:00:00
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更新日期:2007-05-25 00:00:00
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更新日期:1995-04-01 00:00:00
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更新日期:1992-10-01 00:00:00
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更新日期:2004-04-30 00:00:00
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更新日期:1995-03-01 00:00:00
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更新日期:1984-08-01 00:00:00
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更新日期:1975-06-01 00:00:00
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更新日期:1995-02-01 00:00:00