Role of renomedullary thromboxane A2 in development of doca-salt hypertension.
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)F1 alpha 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-PGF1 alpha 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.
Osanai
T
T
2nd Department of Internal Medicine, Hirosaki University School of Medicine, Japan.
Kikuchi
T
T
Yokono
Y
Y
Matsumura
H
H
Minami
O
O
Akiba
R
R
Eidoh
H
H
Konta
A
A
Kanazawa
T
T
Onodera
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D003900:Desoxycorticosterone; D004032:Diet; D015777:Eicosanoids / Q000096:biosynthesis; D006973:Hypertension / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D007679:Kidney Medulla / Q000378:metabolism*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D012077:Renal Artery / Q000378:metabolism; D012964:Sodium / Q000008:administration & dosage; D012965:Sodium Chloride; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D002395:Catecholamines; D015777:Eicosanoids; D008689:Methacrylates; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D013928:Thromboxane A2; D012964:Sodium; D013930:Thromboxane-A Synthase; C034364:ozagrel