TY - JOUR
T1 - Increasing cyclic GMP attenuates cyclic AMP-induced increases in inotropy and oxygen consumption
AU - Leone, R. J.
AU - Straznicka, M.
AU - Scholz, P. M.
AU - Weiss, H. R.
PY - 1998/3/20
Y1 - 1998/3/20
N2 - We tested the hypothesis that increasing myocardial cyclic GMP would attenuate the positive inotropy and O2 consumption caused by increasing cyclic AMP levels. Twenty-four open chest, anesthetized New Zealand white rabbits were divided into four groups and received topical epicardial application of control vehicle (CON), isoproterenol 10-4M (ISO), 3-morpholinosyndnonimine 10-4M, (SIN-1), or a combination of ISO+SIN-1. Coronary blood flow (radioactive microspheres) and O2 extraction (microspectrophotometry) were used to calculate O2 consumption in both subepicardial (EP) and subendocardial (EN) tissue. Left ventricular percent change in wall thickness (%) was increased by ISO (31.1±5.7) from CON (16.0±4.3), and unchanged by either SIN-1 (17.5±1.4) or ISO+SIN-1 (17.1±0.7). Myocardial O2 consumption (ml O2/min/100g) was increased by ISO (13.1±2.3 EP, 15.9±2.0 EN) from CON (10.2±1.0 EP, 11.1±1.0 EN), decreased by SIN-1 (9.7±0.8 EP, 9.9±1.5 EP), and unchanged by ISO+SIN-1 (10.9±0.5 EP, 11.4±1.2 EN). Cyclic AMP (pmol/g) was increased by ISO (725±106 EP, 756±148 EN) from CON (496±46 EP, 534±44 EN) and unaffected by SIN-1 (543±4 EP, 549±50 EN). Isoproterenol induced increases in cAMP did not occur in the ISO+SIN-1 group (537±59 EP, 508±52 EN). Cyclic GMP (pmol/g) was unchanged by ISO (12±2 EP, 10±2 EN) from CON (9±1 EP, 10±1 EN), and increased by both SIN-1 (19±2 EP, 17±3 EN) and ISO+SIN-1 (16±3 EP, 15±3 EN). The current study demonstrates that cAMP mediated increases in inotropy and O2 consumption are attenuated by increasing cGMP using SIN-1. This appears, in part, to be related to cGMP-induced reduction in cAMP.
AB - We tested the hypothesis that increasing myocardial cyclic GMP would attenuate the positive inotropy and O2 consumption caused by increasing cyclic AMP levels. Twenty-four open chest, anesthetized New Zealand white rabbits were divided into four groups and received topical epicardial application of control vehicle (CON), isoproterenol 10-4M (ISO), 3-morpholinosyndnonimine 10-4M, (SIN-1), or a combination of ISO+SIN-1. Coronary blood flow (radioactive microspheres) and O2 extraction (microspectrophotometry) were used to calculate O2 consumption in both subepicardial (EP) and subendocardial (EN) tissue. Left ventricular percent change in wall thickness (%) was increased by ISO (31.1±5.7) from CON (16.0±4.3), and unchanged by either SIN-1 (17.5±1.4) or ISO+SIN-1 (17.1±0.7). Myocardial O2 consumption (ml O2/min/100g) was increased by ISO (13.1±2.3 EP, 15.9±2.0 EN) from CON (10.2±1.0 EP, 11.1±1.0 EN), decreased by SIN-1 (9.7±0.8 EP, 9.9±1.5 EP), and unchanged by ISO+SIN-1 (10.9±0.5 EP, 11.4±1.2 EN). Cyclic AMP (pmol/g) was increased by ISO (725±106 EP, 756±148 EN) from CON (496±46 EP, 534±44 EN) and unaffected by SIN-1 (543±4 EP, 549±50 EN). Isoproterenol induced increases in cAMP did not occur in the ISO+SIN-1 group (537±59 EP, 508±52 EN). Cyclic GMP (pmol/g) was unchanged by ISO (12±2 EP, 10±2 EN) from CON (9±1 EP, 10±1 EN), and increased by both SIN-1 (19±2 EP, 17±3 EN) and ISO+SIN-1 (16±3 EP, 15±3 EN). The current study demonstrates that cAMP mediated increases in inotropy and O2 consumption are attenuated by increasing cGMP using SIN-1. This appears, in part, to be related to cGMP-induced reduction in cAMP.
UR - http://www.scopus.com/inward/record.url?scp=33749350495&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749350495&partnerID=8YFLogxK
M3 - Article
SN - 0892-6638
VL - 12
SP - A979
JO - FASEB Journal
JF - FASEB Journal
IS - 5
ER -