The new NO donor SPM3672 increases cGMP and improves contraction in rat cardiomyocytes and isolated heart.
Recent evidence indicates that organic nitrate esters may directly affect heart muscle. In the present study we investigated the effects of the new organic nitrate ester, N-(3-nitratopivaloyl)-1-cysteineethylester (SPM3672), on isolated adult rat ventricular myocytes and on Langendorff preparations of spontaneously beating rat hearts perfused in a volume-constant manner. In cardiomyocytes SPM3672 (100 microM) induced a significant increase in the basal level of cGMP to 232 +/- 44% (n=8) indicating its metabolism to nitric oxide. This was associated with an enhanced contractile response to electrical field stimulation (to 174 +/- 9%, n=108). In isolated hearts SPM3672 elicited a slight reduction of coronary perfusion pressure (-15 +/- 8%) and a significant increase in maximal left ventricular pressure (LVPmax), dp/dtmax and dp/dtmin amounting to 18 +/- 7%, 18 +/- 6% and 21 +/- 7% (n=7), respectively. Oxygen consumption and heart rate remained constant. Thus, SPM3672 improved the contractile response of cardiomyocytes and of isolated heart. This is probably due to the metabolism of SPM3672 to nitric oxide in ventricular cardiomyocytes.
Kojda
G
G
Institut für Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
Brixius
K
K
Kottenberg
K
K
Nix
P
P
Schlüter
K D
KD
Piper
H M
HM
Noack
E
E
D000818:Animals; D006152:Cyclic GMP / Q000096:biosynthesis*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009566:Nitrates / Q000378:metabolism / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D009566:Nitrates; D014665:Vasodilator Agents; C083079:N-(3-nitratopivaloyl)cysteine ethyl ester; D009569:Nitric Oxide; D006152:Cyclic GMP; D003545:Cysteine