A Comparative Study of C19 Steroid-Induced Hypertension and Deoxycorticosterone Acetate (DOCA)-Salt Hypertension

Abstract

In order to evaluate the hypertensinogenic action of 19-hydroxyandrostenedione (19-OH-AD), which has been reported to be an amplifier of mineralocorticoid, the changes in several humoral factors were observed in 19-OH-AD treated rats as compared to those in DOCA hypertensive rats.Twenty-five male Wistar rats were castrated at 11 weeks of age, and the experiments were begun at 12 weeks of age. The rats were divided into 3 groups. The control group (n = 8) was given an s.c. injection of 0.2 ml of sesame oil. The 19-OH-AD group (n = 10) was injected s.c. with 10 mg of 19-OH-AD dissolved in 0.2 ml of sesame oil, and the DOCA group (n = 8) was injected s.c. with 10 mg of DOCA dissolved in 0.2 ml of sesame oil three time weekly. The urine was collected for a period of 24 hours, and the urine volume, and urinary excretions of electrolytes, prostaglandin E2 (PGE2), kinin and catecholamine were measured before and after the start of the experiment. The systolic blood pressure (S.B.P.) was measured by the tail-cuff method.The S.B.P. values before and at 9 weeks after the start of the experiments were 136.7 ± 3.8 and 156.0 ± 2.6 mmHg in the 19-OH-AD group, and 140.6 ± 5.6 and 179.3 ± 5.5 mmHg in the DOCA group, respectively. Body weight, which was elevated in both groups, was higher in the 19-OH-AD group than in the DOCA group. Water intake and urine volume were significantly (p<0.001) increased only in the DOCA group. The urinary Na/K ratio was significantly (p<0.001) elevated in the DOCA group as compared to that in the other two groups. However, there was no significant difference in urinary Na/K ratio between the control and 19-OH-AD groups. The urinary PGE2 and kinin excretions were significantly (p<0.01) increased in the DOCA group but did not change appreciably in the 19-OH-AD group. The urinary catecholamine excretion was significantly increased in the DOCA group. However, there were no differences in the catecholamine excretion between the control and 19-OH-AD groups.These experimental results suggest that the mechanism of the hypertensinogenic action of 19-OH-AD differs from that of mineralocorticoid dependent hypertension, such as DOCA hypertension, since the urinary Na/K ratio, and the urinary excretions of PGE2, kinin and catecholamine did not change appreciably during the elevation of blood pressure induced by the 19-OH-AD administration.