Angiotensin II receptor and postreceptor events in adrenal glomerulosa cells from streptozotocin-induced diabetic rats with hypoaldosteronism.
Streptozotocin-induced chronic diabetic rats develop hyporeninemic hypoaldosteronism. The hypoaldosteronism is associated with selective unresponsiveness of aldosterone to angiotensin II (AII) and an atrophy of the zona glomerulosa. To assess the nature of the adrenal unresponsiveness to AII, we examined the [125I]monoiodoAII binding and the responses of pregnenolone formation and aldosterone production to AII using adrenal glomerulosa cells from diabetic rats 6 weeks after an injection of streptozotocin. Comparisons were made using the cells from control rats treated with vehicle. Diabetic rats had low levels of plasma renin activity, plasma 18-hydroxycorticosterone, and plasma aldosterone, and normal levels of plasma corticosterone and plasma potassium. The zona glomerulosa width was narrower in diabetic than in control rats. Scatchard analysis of the AII binding data demonstrated that the number and affinity of the receptors were similar in the cells from control and diabetic rats. When corrected to an uniform number of cells per group, baseline levels of pregnenolone formation and aldosterone production were similar in the cells from control and diabetic rats. However, cells from diabetic rats had a less sensitive and lower response of both pregnenolone formation and aldosterone production to AII. In contrast, the effect of ACTH on pregnenolone formation and aldosterone production was similar in the cells from control and diabetic rats. These results indicate that the main defect responsible for the hypoaldosteronism may be located on some step(s) mediating between AII receptors and conversion of cholesterol to pregnenolone, presumably on the calcium messenger system, with a disturbance downstream from AII binding.
Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
S
S
Azukizawa
M
M
Kaneko
S
S
Nakano
T
T
Kigoshi
K
K
Uchida
S
S
Morimoto
D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006994:Hypoaldosteronism / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011284:Pregnenolone / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012016:Reference Values; D015384:Zona Glomerulosa / Q000378:metabolism* / Q000473:pathology
D011945:Receptors, Angiotensin; D000450:Aldosterone; D011284:Pregnenolone