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Inhibition of nitric oxide synthase augments the positive inotropic effect of nitric oxide donors in the rat heart
Author(s) -
MüllerStrahl Gerhard,
Kottenberg Karin,
Zimmer HeinzGerd,
Noack Eike,
Kojda Georg
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.00311.x
Subject(s) - inotrope , contractility , nitric oxide , snap , nitric oxide synthase , medicine , chemistry , contraction (grammar) , endocrinology , ventricular pressure , nitroarginine , blood pressure , computer graphics (images) , computer science
1 In this investigation we studied the effects of nitric oxide on contractility and heart rate in normal saline‐perfused rat hearts where shear stress‐induced endothelial NO synthesis substantially contributes to total cardiac NO production. In addition, we sought to estimate the concentrations of exogenous NO producing inotropic effects. 2 We investigated the effects of glyceryl trinitrate (GTN), S‐ nitroso‐d,l‐penicillamine (SNAP), sodium ( Z)‐ 1‐( N,N‐ diethylamino)diazen‐1‐ium‐1,2‐diolat (DEA/NO), and DEA/NO in the presence of the NO synthase inhibitor N ω ‐nitro‐ l ‐arginine (L‐NA) in constant‐flow‐perfused spontaneously beating rat Langendorff hearts and in rat working hearts. 3 In Langendorff hearts, GTN (10 n m to 100 μ m , n = 32 ) induced a positive inotropic response that plateaued at 1 μ m GTN with a maximal rate of increase of left ventricular pressure during ventricular contraction (+d P /d t max ) of 6.33 ± 2.56 % ( n = 11, P < 0.5). Similarly, both spontaneous NO donors (0.1 n m to 1 μ m , corresponding to approximately 0.03‐0.3 μ m NO) induced a positive inotropic response of 10.6 ± 3.1 % (SNAP; n = 15, P < 0.05) and 11.5 ± 2.7 % (DEA/NO, n = 15 , P < 0.05). 4 The positive inotropic effect of SNAP and DEA/NO progressively declined from 1 μ m to 100 μ m of the NO donors (corresponding to approximately 0.3‐30 μ m NO). 5 In the isolated working rat heart, 0.1 μ m DEA/NO induced an increase of +d P /d t max of 7.5 ± 2.5 % ( n = 9, P < 0.05). Inhibition of NO synthase by L‐NA produced a 4‐fold increase in this effect of DEA/NO. 6 We suggest that physiological NO concentrations support myocardial performance. In normal rat hearts the positive inotropic effect of NO appears to be almost maximally exploited by the endogenous NO production.