Physiological concentrations of nitric oxide do not elicit an acute negative inotropic effect in unstimulated cardiac muscle.
We examined the effect of several nitric oxide (NO) donors, authentic NO gas, and L-arginine in isolated cat and rat papillary muscles. We did not observe significant inotropic effects in response to any NO donor (ie, SPM-5185, C87-3754, and S-nitroso-N-acetylpenicillamine [SNAP]) from 1 nmol/L to 100 mumol/L. Similarly, authentic NO, at concentrations far in excess of those that maximally dilate the coronary vasculature (ie, 500 nmol/L), also failed to exert a detectable inotropic effect in these preparations. However, in the presence of 5 mumol/L norepinephrine, 500 nmol/L NO exerted a 12 +/- 3% decrease in isolated rat papillary muscle contractility (P < .05). Addition of L-arginine up to 25 mmol/L exerted no inotropic effects in isolated rat papillary muscles. However, at 50 mmol/L, L-arginine decreased contractile force by 21 +/- 4% (P < .01). On further examination, the negative inotropic effect of 50 mmol/L L-arginine appeared to be nonspecific, since the inactive stereoisomer, D-arginine, at 50 mmol/L exerted the same effect. Further studies in isolated adult rat cardiac myocytes elicited similar results, in that 50 mmol/L of L- and D-arginine equally decreased contraction amplitude and the underlying cytosolic calcium transient. Moreover, 500 nmol/L of the NO donor SPM-5185 only modestly decreased contraction amplitude or intracellular calcium in isolated rat cardiac myocytes. These results indicate that administration of physiological concentrations of exogenous NO does not acutely depress the inotropic state of the rat or cat heart to a physiologically significant extent.(ABSTRACT TRUNCATED AT 250 WORDS)
Weyrich
A S
AS
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa 19107.
Ma
X L
XL
Buerke
M
M
Murohara
T
T
Armstead
V E
VE
Lefer
A M
AM
Nicolas
J M
JM
Thomas
A P
AP
Lefer
D J
DJ
Vinten-Johansen
J
J
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002415:Cats; D003331:Coronary Vessels / Q000187:drug effects; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D009569:Nitric Oxide / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide; D001120:Arginine; D009638:Norepinephrine