Ca antagonists do not alter aldosterone secretion during established Na depletion.
Conscious sheep whose sole adrenal gland had been transplanted to the neck to allow access to the adrenal vasculature were used to study the effect of calcium antagonists on aldosterone secretion. All animals were sodium depleted by uncompensated loss of parotid saliva. The drugs EDTA, verapamil, methoxyverapamil, nisoldipine, lanthanum, propylmethylenedioxyindene, and ryanodine were infused on separate occasions in three or four increasing dose levels. All infusions were made to produce known concentrations directly into the adrenal arterial blood supply. None of these infusions had any significant effect on aldosterone secretion rate, cortisol secretion rate, and little or no effect on plasma [Na], [K], or blood pressure. At high infusion rates some agents (verapamil, methoxyverapamil) caused tachycardia. In contrast, angiotensin II stimulation of aldosterone secretion is inhibited by both verapamil and nisoldipine. The data demonstrate that the sustained elevation of aldosterone secretion caused by sodium depletion is not dependent on a sustained alteration in transmembrane calcium flux. Furthermore, if circulating angiotensin II is the primary stimulus to aldosterone during sodium depletion, its mechanism of action appears to switch to one which is not dependent on calcium alone.
E I
EI
Johnson
J G
JG
McDougall
J P
JP
Coghlan
D A
DA
Denton
K J
KJ
Hardy
B A
BA
Scoggins
R D
RD
Wright
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D005711:Gallopamil / Q000494:pharmacology; D006854:Hydrocortisone / Q000378:metabolism; D007192:Indenes / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D007811:Lanthanum / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D015737:Nisoldipine; D012433:Ryanodine / Q000494:pharmacology; D012756:Sheep; D012964:Sodium / Q000172:deficiency*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007192:Indenes; D007473:Ion Channels; D012433:Ryanodine; D005711:Gallopamil; D000450:Aldosterone; D015737:Nisoldipine; C027983:2-n-propyl-3-dimethylamino-5,6-methylenedioxyindene; D007811:Lanthanum; D004492:Edetic Acid; D012964:Sodium; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium; D006854:Hydrocortisone