Beta adrenergic and muscarinic receptors in compensatory cardiac hypertrophy of the adult rat.
The beta adrenergic (beta AR) and muscarinic (MR) receptors have been quantitated in parallel, using 125I-pindolol and 3H-quinuclidinylbenzilate, in a model of compensatory left ventricular (LV) hypertrophy (LVH), which developed in rats 4-6 weeks after an abdominal aortic stenosis. Since aortic banding resulted in a pronounced LVH of 62%, the results were expressed both in terms of density (fmol/mg protein) and quantity (fmol per LV). In addition, competition curves using either a specific beta 1-antagonist or isoproterenol or carbachol allowed the determination of the two beta AR subtypes and of the low and high affinity sites (defined by the inhibitory constant Ki) for both beta 1AR and MR. In LVH, receptor density decreased for each of total beta AR, beta 1AR subtype, high affinity (Ki 6-8 nM) beta 1AR sites (from 26 +/- 2 to 19 +/- 3 fmol/mg protein, P < 0.05), total MR and high affinity (Ki 12 nM) MR sites (from 63 +/- 6 to 40 +/- 4 fmol/mg protein, P < 0.001). The beta AR and MR densities dropped in parallel so that the MR/beta AR ratio remained unchanged. In sharp contrast (because the LVs were bigger) the quantities of total beta AR, beta 1AR subtype, beta 1AR high affinity sites, total MR and MR high affinity sites per LV were unmodified.(ABSTRACT TRUNCATED AT 250 WORDS)
Mansier
P
P
Unité INSERM U 127, Hôpital Lariboisière, Paris, France.
Chevalier
B
B
Barnett
D B
DB
Swynghedauw
B
B
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001024:Aortic Valve Stenosis / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007545:Isoproterenol / Q000493:pharmacokinetics; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011813:Quinuclidinyl Benzilate / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*
D007457:Iodine Radioisotopes; D008565:Membrane Proteins; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol