PMID- 12955404 OWN - NLM STAT- MEDLINE DCOM- 20040601 LR - 20131121 IS - 0300-8428 (Print) IS - 0300-8428 (Linking) VI - 98 IP - 5 DP - 2003 Sep TI - Negative effect of nitric oxide on shortening-frequency relationship in cardiac myocytes is diminished after simulated ischemia-reperfusion. PG - 311-8 AB - Increasing stimulation rate increases function in cardiac myocytes and nitric oxide and cyclic GMP inhibit this effect. We tested the hypothesis that myocyte stunning would blunt both the effects of increases in rate and of nitric oxide and cyclic GMP. Ventricular myocytes from 11 rabbits were used to determine maximum rate of shortening (R(max), microm/s) and % shortening during control and after simulated ischemia [15 min 95% N(2)- 5% CO(2)] and reperfusion [reoxygenation]. Measurements were obtained at 1-4 Hz with vehicle, 1H[1,2,4]oxadiazolo[4,3,alpha] quinoxaline-1-one (ODQ) 10(-6) M, soluble guanylyl cyclase inhibitor, or N(G)-nitro-L-arginine methyl ester, nitric oxide synthase inhibitor (L-NAME) 10(-5) M. In control, increases in rate increased R(max) from 69 +/- 3 to 254+/-12 and % shortening from 5.3 +/- 0.3 to 8.7 +/- 0.5. Both ODQ and L-NAME shifted values higher. With stunning, the effects of pacing on Rmax and % shortening were blunted and ODQ and L-NAME failed to alter these values. Cyclic GMP was 322+/-37 pmol/10(5) myocytes at baseline and these values were lowered by ODQ (244 +/- 31) and LNAME (207 +/- 23), and similar changes were observed in stunned myocytes. Increasing frequency increased function, and reducing nitric oxide/cyclic GMP enhanced this relationship. The effect of nitric oxide was diminished by stunning, but this was not related to altered cyclic GMP levels. This suggested changes in effects of cyclic GMP downstream to its production during myocardial stunning. FAU - Weiss, Harvey R AU - Weiss HR AD - Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854-5635, USA. hweiss@umdnj.edu FAU - Gandhi, Ankur AU - Gandhi A FAU - Scholz, Peter M AU - Scholz PM LA - eng PT - Journal Article DEP - 20030719 PL - Germany TA - Basic Res Cardiol JT - Basic research in cardiology JID - 0360342 RN - 31C4KY9ESH (Nitric Oxide) RN - H2D2X058MU (Cyclic GMP) SB - IM MH - Animals MH - Cell Size MH - Cyclic GMP/*metabolism MH - *Heart Rate MH - *Myocardial Reperfusion Injury/pathology/physiopathology MH - Myocardial Stunning/etiology/metabolism/pathology/*physiopathology MH - Myocytes, Cardiac/*metabolism/pathology MH - Nitric Oxide/*metabolism MH - Rabbits EDAT- 2003/09/05 05:00 MHDA- 2004/06/02 05:00 CRDT- 2003/09/05 05:00 PHST- 2002/11/21 00:00 [received] PHST- 2003/05/19 00:00 [revised] PHST- 2003/06/03 00:00 [accepted] PHST- 2003/09/05 05:00 [pubmed] PHST- 2004/06/02 05:00 [medline] PHST- 2003/09/05 05:00 [entrez] AID - 10.1007/s00395-003-0425-8 [doi] PST - ppublish SO - Basic Res Cardiol. 2003 Sep;98(5):311-8. doi: 10.1007/s00395-003-0425-8. Epub 2003 Jul 19.