Altered alpha 1-adrenoceptor-mediated responses in atria of rats with chronic left ventricular infarction.
Phosphoinositide (PI) turnover, chronotropic and inotropic responses to alpha 1-adrenoceptor activation, and alpha 1-adrenoceptor density were studied in atria from rats with left ventricular myocardial infarction (LVMI) and noninfarcted rats. LVMI was produced after surgical ligation of the left coronary artery in 8-week-old Wistar rats. Rats were killed 4 weeks after this operation when rats with LVMI had developed significant hypertrophy of both ventricles and atria. Phenylephrine 0.1 mM to 1 mM, with propranolol 0.3 mM, produced a concentration-dependent increase in heart rate (HR) in right atria from noninfarcted rat hearts, and this response was significantly reduced in rats with LVMI. In electrically driven left atria, the concentration-dependent, phenylephrine-induced positive inotropic responses observed with propranolol added were also significantly impaired in rats with LVMI as compared with those of noninfarcted rats. In contrast, neither PI turnover in response to phenylephrine in the presence of propranolol nor alpha 1-adrenoceptor density was reduced in rats with LVMI. These results suggest that the impaired alpha 1-adrenoceptor-induced chronotropic and inotropic responses in atria from rats with LVMI are not due to downregulation of alpha 1-adrenoceptors or to impaired activation of PI turnover after alpha 1-adrenoceptor stimulation, but to impairment of one or more biochemical responses distal to PI hydrolysis or changes in coupling mechanisms other than hydrolysis of PIs.
Rowley
K G
KG
University of Melbourne, Department of Medicine, Austin.
Tung
L H
LH
Hodsman
G P
GP
Howes
L G
LG
Jarrott
B
B
Beart
P M
PM
Louis
W J
WJ
D000818:Animals; D002908:Chronic Disease; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000503:physiopathology*; D009929:Organ Size; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D011224:Prazosin