Effects of DOCA-salt treatment on the urinary prostaglandins in Sabra rats

Abstract

To determine whether the increased renal synthesis of thromboxane (Tx)A2 found in genetically hypertensive rats also occurred in rats with a sodium-dependent form of hypertension, the urinary excretion of 6-keto-prostaglandin F1 alpha (6KPGF1 alpha) and of TxB2 was measured by a sensitive and specific radioimmunoassay in hypertension-prone (SBH), -resistant (SBN) and unselected (SB) female rats of the Sabra strains. Rats of the three strains were studied before (9 weeks of age) and after five weeks of deoxycorticosterone (DOCA)-salt treatment. Before treatment, the urinary 6KPGF1 alpha did not differ among the three strains while a higher TxB2 excretion was seen in the SBN rats. After treatment, the urinary excretion of TxB2 increased significantly in SBH and SB but not in SBN rats, while the urinary 6KPGF1 alpha remained unchanged in SBH, increased moderately in SB and markedly in SBN controls. Consequently, DOCA-salt-induced changes in blood pressure and in urinary 6KPGF1 alpha observed in the three strains of rats were inversely related (r = -0.78; P less than 0.001). It is concluded that the high blood pressure developed after DOCA-salt treatment in SBH rats is more likely to depend upon a defect in the renal production of prostacyclin rather than upon an increased synthesis of thromboxane A2.

Thromboxane A2 and development of genetic hypertension in the Lyon rat strain.

“…In another model of genetic hypertension, the Lyon model, 9 we described a higher TxA 2 renal production in young (5-and 9-week-old) but not in adult Lyon genetically hypertensive (LH) rats compared with their two control normotensive strains. 10 Such an alteration in TxA 2 biosynthesis seems to be specific to genetic hypertension, as it is not found in models that 12 rats. The antihypertensive effect of chronic Tx synthetase inhibition in SHR led to controversial observations.…”