The AT2 receptor-mediated stimulation of adrenal catecholamine release may potentiate the AT1 receptor-mediated aldosterone secretagogue action of angiotensin-II in rats.
The role played by AT1 and AT2 receptors in the mediation of angiotensin-II (ANG-II) aldosterone secretagogue action has been investigated in vitro using different types of rat adrenal preparations. ANG-II enhanced aldosterone secretion of dispersed zona glomerulosa (ZG) cells in a concentration-dependent manner (EC50, 3 x 10(-10) M), and its effect was annulled by the AT1-receptor antagonist DuP753 and unaffected by the AT2-receptor antagonist PD123319. ANG-II was significantly more effective in stimulating aldosterone secretion when capsule-ZG and adrenal slices containing medullary chromaffin cells were used (EC50, 1 x 10(-11) M and 7 x 10(-12) M, respectively); moreover, both DuP753 and PD123319 caused partial reversals (intense and moderate, respectively) of the responses to ANG-II, and when added together annulled them. The beta-adrenoceptor antagonist l-alprenolol did not affect aldosterone response to ANG-II of dispersed ZG cells, but exerted a PD123319-like effect on the responses of capsule-ZG and adrenal slices. In light of these findings we conclude that, when the integrity of adrenal tissue is preserved, ANG-II stimulates aldosterone secretion by activating both AT1 and AT2 receptors, the major role being played by AT1 receptors located on ZG cells. The activation of AT2 receptors probably elicits the local release of catecholamines, which in turn enhance aldosterone secretion in a paracrine manner acting through the beta-adrenoceptors with which ZG cells are provided.
Mazzocchi
G
G
Department of Anatomy, University of Padua, Italy.
Gottardo
G
G
Macchi
V
V
Malendowicz
L K
LK
Nussdorfer
G G
GG
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D000526:Alprenolol / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D002395:Catecholamines; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C073402:PD 123319; D000450:Aldosterone; D000526:Alprenolol; D019808:Losartan