Nitric oxide donor FK409 and 8-bromoguanosine-cyclic monophosphate attenuate cardiac contractility assessed by Emax.
FK409 decomposes and releases nitric oxide (NO) spontaneously when it is dissolved in phosphate buffer solution at 37 degrees C. With the use of this NO donor, the effect of exogenous NO on cardiac contractility was examined by assessing Emax. alpha-chloralose-anaesthetized dogs were instrumented for measurements of left ventricular (LV) pressure and volume and coronary blood flow (CBF) in the left anterior descending artery (LAD). FK409, 8-bromoguanosine-cyclic-monophosphate (8-Br-cGMP) and papaverine were infused into the LAD, and Emax was determined by transient inferior vena cava occlusion when CBF was increased and reached its peak. Neither drug affected heart rate nor LV pressure just before the measurement of Emax. FK409 increased CBF and decreased Emax in a dose-dependent manner. 8-Br-cGMP also increased CBF and decreased Emax in a dose-dependent manner. Pretreating with propranolol did not affect the effects of FK4098-Br-cGMP on CBF and Emax. Papaverine increased mean CBF but did not affect Emax. In conclusion NO attenuates cardiac contractility in vivo, while increasing CBF. This effect seems to be mediated by cyclic-guanosine monophosphate, a second messenger of NO.
Hiraga
H
H
Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki University, Hirosaki, Japan.
Okubo
T
T
Suto
N
N
Yamamoto
T
T
Yoshida
I M
IM
Okumura
K
K
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009574:Nitro Compounds / Q000494:pharmacology*; D010208:Papaverine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009574:Nitro Compounds; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; C016276:8-bromocyclic GMP; C061872:FK 409; D011433:Propranolol; D010208:Papaverine; D006152:Cyclic GMP