Steroid antagonism of the 'hypertensinogenic' activity of 9 alpha-fluoroprednisolone.
We have previously reported that adrenocortical steroids raise blood pressure by a 'hypertensinogenic' mechanism of action which is not simply related to their classical 'mineralocorticoid' or 'glucocorticoid' actions. This study presents evidence for specific antagonism of this 'hypertensinogenic' activity. The effects of separate IV infusions of prednisolone (P) 100 mg/d and 9 alpha-fluoro-prednisolone (9 alpha F-P) 0.6 mg/d on mean arterial pressure (MAP), plasma [K], plasma [glucose] and urinary Na excretion (UNaV) after 2 days were studied in sheep. In the same group of sheep which received P alone for 2 days, 9 alpha F-P was given for a further 2 days while continuing the P infusion (P + 9 alpha F-P). P alone had no effect on MAP or plasma [K] or UNaV but increased plasma [glucose], effects which are characteristic of 'glucocorticoid' activity. 9 alpha F-P alone increased MAP by 14 mmHg (P less than 0.001) and reduced plasma [K] and UNaV but had no effect on plasma [glucose]. Thus 9 alpha F-P exhibited both 'hypertensionogenic' and 'mineralocorticoid' activity. In the sheep which received the combined P + 9 alpha F-P infusion, the increase in MAP normally produced by 9 alpha F-P was blocked. Although pretreatment with P blocked the pressor effect of 9 alpha F-P, it did not alter the 'mineralocorticoid' effects, namely hypokalaemia and urinary Na retention, produced when 9 alpha F-P was infused alone. These results provide further evidence for our concept of a 'hypertensinogenic' class of steroid activity and are the first demonstration of specific antagonism of steroid induced hypertension.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects*; D005477:Fluprednisolone / Q000037:antagonists & inhibitors* / Q000031:analogs & derivatives; D005938:Glucocorticoids / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced; D008297:Male; D008901:Mineralocorticoids / Q000494:pharmacology; D011188:Potassium / Q000097:blood; D011239:Prednisolone / Q000494:pharmacology; D012756:Sheep; D012964:Sodium / Q000652:urine
D000305:Adrenal Cortex Hormones; D001786:Blood Glucose; D005938:Glucocorticoids; D008901:Mineralocorticoids; C010958:9-fluoroprednisolone; D005477:Fluprednisolone; D012964:Sodium; D011239:Prednisolone; D011188:Potassium