Nitric oxide enhances the inotropic response to β-adrenergic stimulation in the isolated guinea-pig heart |
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Authors: | BD Prendergast P MacCarthy JF Wilson AM Shah |
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Institution: | (1) Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff, CF4 4XN, United Kingdom, E-mail: shaham2@cf.ac.uk, GB;(2) Department of Pharmacology, University of Wales College of Medicine, Heath Park, Cardiff, CF4 4XN, United Kingdom, GB |
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Abstract: | Nitric oxide (NO) exerts several effects on myocardial contraction, including enhancement of relaxation and diastolic function,
modulation of β-adrenergic inotropic responses, and inotropic effects in the absence of agonist pre-stimulation. Different
effects have been observed in different species and preparations, and it is unclear whether they are species- or preparation-specific,
or whether they represent a range of responses that can manifest in most mammalian species. We therefore examined the effects
of NO on the inotropic response to β-adrenergic stimulation in the isolated guinea-pig heart, a species in which we have previously
shown that NO enhances basal left ventricular (LV) relaxation and modulates the Frank-Starling response. Isolated ejecting
hearts were perfused with Krebs buffer at constant paced heart rate (1 μM indomethacin, 37°C, constant loading conditions),
and high fidelity LV pressure was monitored by an apical 2F Millar catheter. All hearts were initially treated with dobutamine
(0.1 μM) and then, once the peak inotropic and chronotropic response had been established, with either (a) no further treatment
(n=6), (b) the NO donor sodium nitroprusside (1 μM, n=6; 10 μM, n=6), or (c) the specific agonist for NO release, substance
P (0.1 μM, n=6). Dobutamine (0.1 μM) produced a rapid positive inotropic and chronotropic response, associated with a fall
in LV end-diastolic pressure (LVEDP) and a rise in coronary flow. The positive inotropic effect of dobutamine declined over
20–28 minutes, while the chronotropic response persisted over this period. Low dose sodium nitroprusside (1 μM) delayed the
decline in the inotropic response to dobutamine and exaggerated the fall in LVEDP. Similar effects were observed with substance
P (0.1 μM). In contrast, a higher dose of sodium nitroprusside (10 μM) did not alter the response to dobutamine. These data
indicate that “low dose” NO augments the inotropic response to β-adrenergic stimulation in the isolated ejecting guinea-pig
heart, in addition to its previously reported effects on basal LV relaxation in the same preparation.
Received: 3 September 1997, Returned for revision: 30 September 1997, Revision received: 16 December 1997, Accepted: 19 January
1998 |
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Keywords: | Myocardium – inotropism – nitric oxide – β -adrenergic – guinea-pig |
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