Reduction of cardiac norepinephrine improves postischemic heart function in stroke-prone spontaneously hypertensive rats.
Although mammalian ventricle is richly supplied with adrenergic nerves, endogenous norepinephrine is not essential to the intrinsic contractility of the normal heart. However, it is not clear whether acute changes in cardiac norepinephrine could alter heart function in genetically hypertensive rats. The purpose of this study was to examine the effect of cardiac norepinephrine reduction on basal and postischemic heart function in stroke-prone spontaneously hypertensive rats (SHRSPs) using an isolated working heart preparation. Hypertrophied hearts of SHRSPs showed higher cardiac norepinephrine content and impaired heart function at 4 months of age as compared with normal Wistar-Kyoto rats. Poor postischemic recovery of heart function observed in SHRSPs was accompanied by large amounts of coronary norepinephrine overflow. Cardiac norepinephrine reduction or depletion did not affect basal heart function in SHRSPs. Considerable reduction in cardiac norepinephrine with acute reserpine injection (5 mg/kg) in SHRSPs significantly improved postischemic recovery of cardiac output, coronary flow, and rate-pressure product. However, complete norepinephrine depletion with reserpine (10 mg/kg) was detrimental to myocardial automaticity and limited the postischemic recovery of systolic function in the hypertrophied hearts. These results suggest that acute reduction in cardiac norepinephrine may be of potential therapeutic importance to postischemic dysfunction in the hypertrophied hearts.
Chen
H
H
Department of Pharmacology, Second Military Medical University, Shanghai, China. hchen100@hotmail.com
Higashino
H
H
Maeda
K
K
Zhang
Z
Z
Ohta
Y
Y
Wang
Z
Z
Su
D F
DF
Yuan
W J
WJ
D000818:Animals; D002302:Cardiac Output; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000378:metabolism; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009638:Norepinephrine / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012110:Reserpine / Q000494:pharmacology; D020521:Stroke / Q000378:metabolism* / Q000503:physiopathology*; D013318:Stroke Volume
D012110:Reserpine; D003402:Creatine Kinase; D009638:Norepinephrine