Altered intracellular adrenoceptor distribution in myocardium of spontaneously hypertensive rats.
The number of membrane-bound beta-adrenoceptors is reduced in the myocardium of spontaneously hypertensive rats, and this decline may account for the decreased inotropic responsiveness to beta-agonists. It is not known, however, whether the total complement of cellular beta-receptors is lower in hypertensive animals. This issue was examined using two different approaches: acid elution of cell surface-bound beta-receptor ligands and comparison of the number of receptors in the plasma membrane and a postcytosolic vesicular fraction. Approximately 30% of the total beta-receptors were located intracellularly in Wistar-Kyoto rats compared with 42% for spontaneously hypertensive rats. Similarly, a decline in membrane-bound beta-receptors in hypertensive rats was balanced by a rise in receptors associated with the vesicular fraction. In contrast, alpha 1-adrenoceptors were higher in the membrane and lower in the vesicular fraction of hypertensive rats without a significant difference in total alpha-receptors compared with normotensive animals. Differences in adrenergic responsiveness in this, and perhaps other, models of cardiac hypertrophy reflect altered intracellular distribution of adrenoceptors, which may be under the control of the sympathetic nervous system.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology; D002462:Cell Membrane / Q000032:analysis; D003600:Cytosol / Q000032:analysis; D004082:Dihydroalprenolol / Q000378:metabolism; D006973:Hypertension / Q000473:pathology*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology*; D011224:Prazosin / Q000378:metabolism; D011412:Propanolamines / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D014018:Tissue Distribution
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; C033394:CGP 12177; D011224:Prazosin