Myocardial contractile response to nitric oxide and cGMP.
BACKGROUND
Cardiac endothelium releases a number of factors that may modulate performance of underlying cardiac muscle. Nitric oxide (NO), which accounts for the biological activity of the vascular endothelium-derived relaxing factor and relaxes vascular smooth muscle by elevating intracellular cGMP, may be involved in this cardiac modulation.


RESULTS
We examined the myocardial contractile effects of the NO-releasing nitrovasodilators sodium nitroprusside (SNP), 3-morpholino-sydnonimine (SIN-1), and S-nitroso-N-acetyl-penicillamine (SNAP); of a cGMP analogue, 8-bromo-cGMP; and of the cGMP-phosphodiesterase inhibitor zaprinast in isolated cat papillary muscle. Modulation of these effects by endocardial endothelium (EE) and by cholinergic and adrenergic stimulation was also investigated. Concentration-response curves with addition of NO-releasing nitrovasodilators (SNP, SIN-1, SNAP) and 8-bromo-cGMP resulted in a biphasic inotropic response. Although administration of low concentrations induced a positive inotropic effect, higher concentrations induced a negative inotropic effect. Both NO-induced positive and negative inotropic effects were attenuated by methylene blue, suggesting a role for cGMP. The response to high concentrations of 8-bromo-cGMP was shifted to the right in muscles with damaged EE, whereas cholinergic stimulation shifted the curve leftward. Zaprinast caused a monophasic concentration-dependent positive inotropic effect; damaging the EE shifted the terminal portion of the curve upward. Concomitant cholinergic or adrenergic stimulation modified the response to zaprinast into a negative inotropic response.


CONCLUSIONS
NO and cGMP induced a concentration-dependent biphasic contractile response. The myocardial contractile effects of NO and cGMP were modulated by the status of EE and by concomitant cholinergic or adrenergic stimulation.
Mohan
P
P
Department of Physiology and Medicine, University of Antwerp, Belgium.
Brutsaert
D L
DL
Paulus
W J
WJ
Sys
S U
SU
D000818:Animals; D002415:Cats; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine
D011688:Purinones; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; D008981:Molsidomine; D010396:Penicillamine; C011145:zaprinast; D006152:Cyclic GMP