Effects of nitric oxide synthase inhibition on Basal function and the force-frequency relationship in the normal and failing human heart in vivo.
Authors
Cotton, James M.Kearney, Mark T.
MacCarthy, Philip A.
Grocott-Mason, Richard M.
McClean, Dougal R.
Heymes, Christophe
Richardson, Peter J.
Shah, Ajay M.
Issue Date
2001
Metadata
Show full item recordAbstract
BACKGROUND: Nitric oxide (NO) exerts autocrine/paracrine effects on cardiac function, including alterations of the inotropic state. In vitro studies suggest that NO modulates the myocardial force-frequency relationship. Basal left ventricular (LV) contractility is depressed and the force-frequency relationship is blunted in human heart failure, and it is speculated that an increase in NO production is involved. METHODS AND RESULTS: We compared the effects of intracoronary NO synthase inhibition with N(G)-monomethyl-L-arginine (L-NMMA; 25 micromol/min) on basal LV function and the response to incremental atrial pacing in patients with dilated cardiomyopathy (n=11; mean age, 51 years) and in control subjects with atypical chest pain and normal cardiac function (n=7; mean age, 54 years). In controls, L-NMMA significantly reduced basal LV dP/dt(max) (from 1826 to 1578 mm Hg/s; P<0.002), but had no effect on heart rate, mean aortic pressure, or right atrial pressure. Pacing-induced increases in LV dP/dt(max) were unaltered by L-NMMA. In patients with dilated cardiomyopathy, L-NMMA had no effect on baseline LV dP/dt(max) (from 1313 to 1337 mm Hg/s; P=NS). The blunted pacing-induced rise in LV dP/dt(max) in these patients was unaltered by L-NMMA. CONCLUSION: Endogenous NO has a small baseline positive inotropic effect in the normal human heart, which is lost in heart failure patients. NO does not significantly influence the force-frequency relationship in either the normal or failing human heart in vivo. Because this study was performed in patients with moderate heart failure, whether the findings apply to subjects with more severe heart failure requires further investigation.Citation
Circulation, 104(19): 2318-2323Publisher
American Heart Association IncJournal
CirculationPubMed ID
11696472Additional Links
http://circ.ahajournals.org/cgi/content/full/104/19/2318Type
Journal articleLanguage
enISSN
1524-4539ae974a485f413a2113503eed53cd6c53
10.1161/hc4401.098515
Scopus Count
Collections
Related articles
- Nitric oxide spares myocardial oxygen consumption through attenuation of contractile response to beta-adrenergic stimulation in patients with idiopathic dilated cardiomyopathy.
- Authors: Shinke T, Takaoka H, Takeuchi M, Hata K, Kawai H, Okubo H, Kijima Y, Murata T, Yokoyama M
- Issue date: 2000 Apr 25
- Cardiac nitric oxide production due to angiotensin-converting enzyme inhibition decreases beta-adrenergic myocardial contractility in patients with dilated cardiomyopathy.
- Authors: Wittstein IS, Kass DA, Pak PH, Maughan WL, Fetics B, Hare JM
- Issue date: 2001 Aug
- Effect of vitamin C and L-NMMA on the inotropic response to dobutamine in patients with heart failure.
- Authors: Mak S, Overgaard CB, Newton GE
- Issue date: 2005 Dec
- Nitric oxide inhibits the positive inotropic response to beta-adrenergic stimulation in humans with left ventricular dysfunction.
- Authors: Hare JM, Loh E, Creager MA, Colucci WS
- Issue date: 1995 Oct 15
- Increased sensitivity to nitric oxide synthase inhibition in patients with heart failure: potentiation of beta-adrenergic inotropic responsiveness.
- Authors: Hare JM, Givertz MM, Creager MA, Colucci WS
- Issue date: 1998 Jan 20