The inotropic response of the isolated, perfused, working rat heart to norepinephrine is attenuated by inhibition of nitric oxide.
Experiments on isolated, perfused, working left ventricular (LV) hearts of 66 female Wistar rats were done to examine whether nitric oxide (NO) influences the effects of norepinephrine (NE) on coronary flow as well as on contraction and relaxation. Functional parameters were monitored before and after application of NE at a concentration of 3 X 10(-8) M in the absence and presence of the nitric oxide synthase (NOS) inhibitor L-nitro-arginine (L-NA) at a concentration of 1 X 10(-4) M and of the spontaneous NO donor sodium (Z)-1-(N,N-diethylamino) diazen-1-ium-1,2-diolat (DEA/NO) at a concentration of 1 X 10(-7) M. In control experiments, heart rate was varied by electrical stimulation between 200 and 400 beats/min. Within this range of heart rates, coronary flow and cardiac output remained constant, while stroke volume, LV peak pressure and LV dP/dt(max) decreased with increasing heart rate. NE increased coronary flow from 7.6 +/- 0.4 to 9.8 +/- 0.7 ml/min and induced the well-known positive chronotropic and inotropic effects. DEA/NO increased coronary flow; however, the inotropic and lusitropic parameters were not affected. Simultaneous infusion of NE with DEA/NO further increased coronary flow from 9.8 +/- 0.7 to 12.1 +/- 0.8 ml/min without a significant effect on any other functional parameter. When NOS was inhibited by L-NA, the positive inotropic effect of NE was attenuated. Cardiac output, however, was increased, while coronary flow did not change significantly. Under these conditions, NE increased dP/dt(max) by 65.5 +/- 5.8% (from 2999 +/- 97 to 4929 +/- 230 mmHg/s) compared with an increase by 92.8 +/- 6.7% (from 3770 +/- 82 to 7234 +/- 211 mmHg/s) under control conditions. Application of DEA/NO reversed the attenuated inotropic response, but relaxation remained partially impaired. Thus, the presence of NO seems to be necessary for the inotropic effect of NE to become manifest.
Geier
Silvio
S
Carl-Ludwig-Institut für Physiologie, Universität Leipzig, Germany.
Müller-Strahl
Gerhard
G
Zimmer
Heinz-Gerd
HG
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009589:Nitrogen Oxides; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013566:Sympathomimetics / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D006834:Hydrazines; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D013566:Sympathomimetics; D019335:Nitroarginine; D009569:Nitric Oxide; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D019001:Nitric Oxide Synthase; D009638:Norepinephrine