[Production of aldosterone and its precursor steroids by the adrenal zona glomerulosa in dextran sulfate-treated rats].
Heparin and heparinoids are known to produce selective aldosterone deficiency in man and experimental animals. To assess the nature of the hypoaldosteronism caused by heparin and heparinoids, we investigated the production of aldosterone and its precursor steroids in response to angiotensin II (AII), ACTH or potassium in adrenal zona glomerulosa cells from dextran sulfate-treated rats compared with that in the cells from vehicle-treated rats. Dextran sulfate-treated rats had a decrease in plasma aldosterone and a reduction in the width of the zona glomerulosa 4 weeks after the treatment (40 mg/day, intramuscularly). In these rats, PRA and plasma AII tended to be high, and plasma corticosterone was normal. Basal aldosterone production, when corrected to a uniform number of cells per group, was similar in cells from dextran sulfate- and vehicle-treated rats. The cells from dextran sulfate-treated rats had a less sensitive and lower response of aldosterone production to AII; an increase by 4 orders of magnitude in the threshold dose for AII and a decrease in the maximal AII-stimulated level. The maximal AII-stimulated levels, but not the basal levels, of pregnenolone, corticosterone and 18-hydroxycorticosterone production were low in the cells from dextran sulfate-treated rats. ACTH produced a similar stimulatory effect on aldosterone production in the cells from dextran sulfate- and vehicle-treated rats. The cells from dextran sulfate-treated rats had a less sensitive and lower response of aldosterone production to potassium; an increase by one order of magnitude in the threshold dose for potassium and a decrease in the maximum potassium-stimulated level, presumably because of the glomerulosa hyporesponsiveness to AII. These results suggest that long-term treatment with dextran sulfate in rats produces selective impairment of adrenal zona glomerulosa cells, involving the specific receptors and the aldosterone biosynthesis, to AII in addition to a reduction in the glomerulosa width.
Azukizawa
S
S
Uchida
K
K
Imaizumi
N
N
Yamamoto
I
I
Hosojima
H
H
Morimoto
S
S
Konishi
H
H
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis* / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D002784:Cholesterol / Q000097:blood; D003345:Corticosterone / Q000097:blood; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D011188:Potassium / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D012964:Sodium / Q000097:blood
D003911:Dextrans; D008055:Lipids; D000804:Angiotensin II; D000450:Aldosterone; D016264:Dextran Sulfate; D002784:Cholesterol; D012964:Sodium; D012083:Renin; D011188:Potassium; D003345:Corticosterone