Chronic potentiation of vasoconstrictor hypertension by adrenocorticotropic hormone.
The chronic effects of ACTH on mean arterial pressure (MAP) and related variables were studied in dogs with both chronic norepinephrine (NE)- and chronic aldosterone-induced hypertension. MAP was recorded continuously for 24 hours/day, and sodium intake was 71 mEq/day. ACTH was infused for 8 days at a rate that does not increase MAP in normotensive dogs and yet a rate that produces pronounced mineralocorticoid and glucocorticoid effects. Chronic ACTH infusion in dogs with NE hypertension caused natriuresis, kaliuresis, diuresis, hypernatremia, hypokalemia, and suppression of PRA; additionally, there was either no net change in water balance or net water balance was positive. However, in marked contrast to dogs without pre-existing hypertension, in dogs with NE hypertension ACTH produced a pronounced additional increase in MAP of 39 to 63 mm Hg. Although ACTH markedly potentiated NE hypertension, high infusion rates of aldosterone (+6 mm Hg) and cortisol (-7 mm Hg) had relatively weak effects on MAP; further, in dogs with NE hypertension, the increase in MAP associated with simultaneous infusions of high rates of cortisol and aldosterone was equal to only approximately half of that produced by ACTH. In dogs with aldosterone hypertension, the changes in salt and water balance produced by ACTH were comparable to those that occurred when ACTH was administered to dogs with NE hypertension. In dogs with aldosterone hypertension, however, ACTH did not produce kaliuresis, hypernatremia, or hypokalemia; moreover, ACTH did not exacerbate aldosterone hypertension. Thus, the data indicate that the hypertensive effects of ACTH are manifested in conditions of reduced renal excretory capacity such as exist when plasma levels of the potent sodium -retaining hormone NE are inappropriately elevated. Finally, the hypertensive effects of ACTH cannot be accounted for simply on the basis of enhanced mineralocorticoid and glucocorticoid activity.
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000097:blood / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004573:Electrolytes / Q000097:blood; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014882:Water-Electrolyte Balance / Q000187:drug effects
D004573:Electrolytes; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012083:Renin; D006854:Hydrocortisone; D009638:Norepinephrine