Coronary artery constriction in rats affects the activation of alpha 1 adrenergic receptors in cardiac myocytes.
OBJECTIVE
To determine whether alpha 1 adrenergic receptor mediated myocyte contractility and growth are depressed acutely after non-occlusive coronary artery narrowing, the left coronary artery was constricted in rats and mechanical behaviour, cytosolic calcium, and regulation of alpha 1 adrenergic receptors were examined in myocytes seven days later.


METHODS
Coronary artery stenosis was surgically induced in rats and following the estimation of global cardiac performance myocytes were enzymatically dissociated and radioligand binding studies were performed. In addition, the isotonic contractile performance, cytosolic calcium transients and noradrenaline stimulated inositol phosphate generation in myocytes were measured in the presence of WB 4101 or after chlorethylclonidine treatment.


RESULTS
Estimations of cell mechanics in vitro established that peak shortening was decreased by 36% and 18% in left and right ventricular myocytes of coronary stenosed rats. Time to peak shortening was prolonged by 29% in left and 20% in right myocytes, whereas velocity of shortening was decreased by 27% in left myocytes. These alterations were associated with increases in cell length and width, indicative of myocyte hypertrophy. In addition, coronary stenosis was accompanied by reductions in the expression of alpha 1a and alpha 1b receptor subtypes in myocytes. alpha 1 Adrenergic receptor density and noradrenaline stimulated phosphoinositol turnover were decreased by 30% and 34% in left myocytes. alpha 1a Adrenergic receptor subtype mediated cytosolic calcium concentration and myocyte mechanical performance were also impaired in left myocytes only. The alpha 1a adrenergic receptor subtype antagonist WB 4101 abolished noradrenaline stimulated inositol phosphate generation in myocytes, whereas chlorethylclonidine at large doses only partially inhibited this response.


CONCLUSIONS
In conclusion, coronary narrowing leads to defects in the regulation of alpha 1 adrenergic receptors on myocytes which are coupled with attenuation in the transmission of signals, possibly affecting myocyte cell function and ongoing reactive cellular hypertrophy.
New York Medical College, Valhalla 10595.
W
W
Cheng
J
J
Coupet
P
P
Li
K
K
Reiss
C V
CV
Hamby
J M
JM
Capasso
L G
LG
Meggs
P
P
Anversa
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D048429:Cell Size; D002478:Cells, Cultured; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003250:Constriction; D003331:Coronary Vessels; D003600:Cytosol / Q000378:metabolism; D004146:Dioxanes / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D000477:Alkylating Agents; D004146:Dioxanes; D007295:Inositol Phosphates; D018340:Receptors, Adrenergic, alpha-1; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine