Modulation of renin by thromboxane: studies with thromboxane synthase inhibitor, receptor antagonists, and mimetic
Welch, W.J.; Wilcox, C.S.; Dunbar, K.R.
American Journal of Physiology 257(4 Pt 2): F554-F560
1989
ISSN/ISBN: 0002-9513 PMID: 2508488 Document Number: 345139
The regulation of plasma renin activity (PRA) by thromboxane (Tx) A2 was studied in anesthetized rats by measuring PRA before and after administration of drugs that block cyclooxygenase (CO) (ndomethacin [INDO], 5 mg/kg), thromboxane synthase (TS) (UK 38485 [UK], 100 mg/kg), or tx receptors (SQ 29548 [SQ], 8 mg/kg or L 641953 [L], 50 mg/kg) or that activate tx receptors (U 46619 [U], 10 ng .cntdot. kg-1 .cntdot. min-1). PRA (ng ANG I .cntdot. ml-1 .cntdot. h-1) was unaffected by vehicle; it was reduced by INDO (25 .+-. 2 to 13 .+-. 3, n = 13, P < 0.001) but was increased by UK (24 .+-. 3 to 50 .+-. 6, n = 18, P < 0.005), SQ (27 .+-. 4 to 44 .+-. 7, n = 6, P < 0.05), and L (32 .+-. 4 to 51 .+-. 7, n = 10, P < 0.05). U reduced PRA in each rat (17 .+-. 3 to 10 .+-. 3, n = 6, p < 0.005). UK caused dose-dependent stimulation of PRA (mean effective dose 50 mg/kg) and inhibition of txB2 excretin (mean inhibitory dose 15 mg/kg). After INDO, SQ no longer changed PRA (-1 .+-. 10, n = 7). Prolonged administration of SQ for 4-6 days (20 mg .cntdot. kg-1 .cntdot. day-1 ip) di dnot change na+ or K+ balances, blood pressure, renal hemodynamics, or urine flow. However, SQ stimulated PRA (P < 0.007) independent of prior salt intake. In conclusion in anesthetized rats 1) PRA is stimulated by products of CO but inhibited by products of TS and by a Tx mimetic; 2) stimulation of PRA by SQ depends on ongoing PG and Tx synthesis; 3) rise in PRA with Tx antagonists is not closely related to changes in salt balance, blood pressure, or renal hemodynamics.