Adenylyl cyclase regulation in heart failure due to myocardial infarction in rats

作者：Braeunig Jorg H; Albrecht Kuepper Barbara; Seifert Roland^*

来源：Naunyn-Schmiedeberg's Archives of Pharmacology, 2014, 387(4): 389-398.

DOI：10.1007/s00210-013-0943-3

• Adenylyl cyclase
• Heart failure
• Myocardial infarction

Cardiac adenylyl cyclase (AC) activity was described to be differentially regulated in left and right ventricles (LVs and RVs) of rats with heart failure (HF) due to LV myocardial infarction (MI) (Sethi et al. Am J Physiol 272:H884-H893, 1997). AC activities in LVs and RVs were increased and decreased respectively in rats 8 and 16 weeks post MI under basal and stimulatory conditions including AC activation via beta-adrenergic receptors (beta-ARs), stimulatory G protein (G(s)), and direct AC activation with forskolin (FS). The current study aimed to detect alterations in rat heart AC activities in a comparable model of HF 9 weeks post LV MI. Therefore, cardiac AC activities were measured under basal and beta-AR-, G(s)-, or FS-stimulated conditions as well as under inhibition with various MANT [2%26apos;(3%26apos;)-O-(N-methylanthraniloyl)]-nucleotide AC inhibitors and the P-site AC inhibitors NKY80 [2-amino-7-(2-furanyl)-7,8-dihydro-5(6H)-quinazolinone] and vidarabine (9-beta-D-arabinosyladenine, AraAde). Basal and stimulated AC activities along with AC inhibition experiments did not reveal evidence for changes in AC activity in LVs and RVs from MI group animals despite the presence of congestive HF. However, our study is indeterminate. Further studies are required to identify the factors responsible for previously described changes in cardiac AC activity in MI induced HF and to elucidate the role of altered AC regulation in the pathophysiology of HF. In order to detect small changes in AC regulation, larger group sizes than the ones used in our present study are required.

• 出版日期2014-4