Role of Renomedullary Thromboxane A₂ in Development of DOCA-Salt Hypertension

Abstract

To clarify the role of renal thromboxane(TX)A₂ in the development of deoxycorticosterone acetate (DOCA)-salt induced hypertension, relationship between systolic blood pressure and the synthesis of renal TXA₂ was investigated in 18 rats without and with OKY-046 administration which suppressed the synthesis of renal TXA₂.

Systolic blood pressure was significantly higher in DOCA-salt group than in control and OKY groups. The synthesis of 6-keto-prostaglandin(PG)F_1α and TXB₂ in both renal arteries and cortical slices were more enhanced in DOCA-salt and OKY groups than in control group, but there was no significant difference between DOCA-salt and OKY groups. In contrast, the synthesis of 6-keto-PGF_1α in renomedullary slices did not vary significantly among three groups, and that of TXB₂ was more increased in DOCA-salt group than in control and OKY groups. The cumulative sodium retention was significantly greater in DOCA-salt group than in control group. Administration of OKY-046 reduced the cumulative sodium retention in DOCA-salt rats by 45% toward that of the control group.

These results might suggest that the enhanced production of renomedullary TXB₂ was important to the development of DOCA-salt induced hypertension.

Key Words:

• kidney
• thromboxane A₂
• natriuresis
• DOCA-salt hypertension