The characteristics of renal mineralocorticoid receptors in glycyrrhizinic acid or deoxycorticosterone-induced hypertensive rats.
The relationship between blood pressure and the characteristics of renal mineralocorticoid receptors was studied in glycyrrhizinic acid (GR) or deoxycorticosterone (DOC) induced hypertensive rats. The apparent maximum binding (Bmax) of aldosterone to renal mineralocorticoid receptors was 3.1 +/- 0.2 X 10(-13) mol/mg cytosol protein and the dissociation constant (Kd) was 1.6 +/- 0.5 nM. GR treatment reduced the concentration of cytosol mineralocorticoid receptors (Bmax) but did not affect the Kd. In unilaterally adreno-nephrectomized rats, GR induced hypertension and hypokalemia as seen in DOC treated rats. After the discontinuation of GR, blood pressure was normalized with concomitant recovery of free cytosol mineralocorticoid receptors in 14 weeks. On the contrary, in DOC treated rats, the characteristics of mineralocorticoid receptors in kidney were already normal one week after the cessation of DOC treatment. However, blood pressure remained high up to 15 weeks. These findings suggest that the persistence of hypertension after GR discontinuation might be caused by a long-standing effect of GR on renal mineralocorticoid receptor mechanisms.
D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects; D003900:Desoxycorticosterone / Q000494:pharmacology*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019695:Glycyrrhizic Acid; D006973:Hypertension / Q000139:chemically induced*; D007668:Kidney / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D011188:Potassium / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000187:drug effects*; D012964:Sodium / Q000097:blood
D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D003900:Desoxycorticosterone; D000450:Aldosterone; D019695:Glycyrrhizic Acid; D012964:Sodium; D006034:Glycyrrhetinic Acid; D011188:Potassium