Effect of furosemide, hydrochlorothiazide and sodium restriction on rat adrenoceptors.
The interaction of thiazide diuretics and furosemide with adrenoceptors was investigated in normal rat in vivo by determining the effect of sodium-deficient diet alone or combined with hydrochlorothiazide or furosemide on adrenoceptors in heart, kidney and skeletal muscle. In addition, interaction of diuretics with renal adrenoceptors in vitro was investigated. Sodium-deficient diet alone retarded growth significantly, and this effect was increased by simultaneous treatment with furosemide 10-40 mg/kg body weight and day subcutaneously. No consistent alteration was demonstrated in density or affinity of alpha 1-, alpha 2- and beta-adrenoceptors due to the in vivo treatment. In vitro, furosemide inhibited the equilibrium specific binding of radioligands to alpha 1-, alpha 2- and beta-adrenoceptors to rat kidney particulate fraction concentration-dependently. Furosemide increased Kd (equilibrium dissociation constant) and reduced Bmax (number of specific binding sites) of the radioligands as determined by Scatchard analysis of binding saturation data. The Pseudo-Hill coefficient of the inhibition by furosemide of 125I-iodocyanopindolol binding was 1.47, indicating a complex interaction consistent with a non-competitive inhibition. In conclusion, the results do not support the hypothesis that sodium deficiency alone or with diuretic treatment for one week alters tissue adrenoceptors in the normal rat. The pattern of inhibition by furosemide of ligand binding to adrenoceptors suggests that furosemide binds to an allosteric site on the receptors or to an adjacent macromolecule.
Brørs
O
O
Department of Clinical Chemistry, Ullevaal Hospital, Oslo, Norway.
D000818:Animals; D001667:Binding, Competitive; D001835:Body Weight; D004039:Diet, Sodium-Restricted; D005665:Furosemide / Q000494:pharmacology*; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D008024:Ligands; D008297:Male; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000378:metabolism
D008024:Ligands; D011941:Receptors, Adrenergic; D006852:Hydrochlorothiazide; D005665:Furosemide