The effect of nivazol and cortivazol, novel synthetic steroids containing a phenylpyrazolo A-ring substitution, on blood pressure in sheep.
This study investigated the effect of 5 day infusions of two structurally novel synthetic steroids, nivazol and cortivazol on blood pressure and in vivo indices of "glucocorticoid" and "mineralocorticoid" activity. Cortivazol at 24 mg/day raised mean arterial pressure (MAP) by 16 mmHg (P less than 0.001). This was associated with increased cardiac rate, and increased fasting plasma [glucose], polyuria and polydipsia a trilogy characteristic of glucocorticoid effect. Cortivazol had no consistent action on plasma [Na] or [K], but caused an initial transient urinary Na retention and raised urinary excretion of Na and K on days 3 and 4 of treatment. Nivazol at 24 mg/day raised MAP 10 mmHg (P less than 0.001), but cardiac rate was unchanged. This infusion was also associated with the glucocorticoid effects of increased fasting plasma [glucose] and increased urine volume. Plasma [K] fell from a control of 4.4 +/- 0.1 to 4.0 +/- 0.1 mmol/l (P less than 0.01) after 5 days of infusion. There was no significant effect of nivazol on urinary Na or K excretion. This study demonstrates that replacement of the 3-keto group, by a bulky phenylpyrazolo group fused to the A ring at position 2 and 3, does not diminish either pressor or glucocorticoid activity of steroids containing the typical 4-pregnene-3,20-dione nucleus and confirms that the 3 keto group is not essential for optimal glucocorticoid activity. It is the first demonstration of the pressor effect of these novel steroids.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004326:Drinking; D005260:Female; D006339:Heart Rate; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine; D011245:Pregnadienes / Q000494:pharmacology*; D011281:Pregnatrienes / Q000494:pharmacology*; D012756:Sheep; D013329:Structure-Activity Relationship
D011245:Pregnadienes; D011281:Pregnatrienes; C041704:nivazol; D011188:Potassium; C005924:cortivazol