Thromboxane synthase and TP receptor mRNA in rat kidney and brain: effects of salt intake and ANG II.

A TP receptor (TP-R) mimetic causes salt-sensitive hypertension and renal afferent arteriolar vasoconstriction. TP-Rs mediate effects of ANG II on renal vascular resistance and drinking. Therefore, we investigated the hypothesis that thromboxane A(2) synthase (TxA(2)-S) and/or TP-R expression is regulated by salt and/or ANG II. Rats (n = 6) received high-salt (HS) or low-salt (LS) diets. Additional HS-diet rats received ANG II while other HS- and LS-diet rats received the AT(1) receptor (AT(1)-R) antagonist losartan. Excretion of thromboxane B(2) by conscious rats was increased with the HS diet compared with the LS diet (126 +/- 10 vs. 48 +/- 5 pmol/24 h, respectively; P < 0.01). The mRNA abundance for TP-Rs (relative to beta-actin) in the kidney cortex was enhanced 30% by the HS diet (P < 0.001) and was reduced 50% by the addition of ANG II (P < 0.001). However, during losartan administration, the effects of salt were reversed; mRNA more than doubled during the LS diet (P < 0.001). Similarly, the mRNA abundance for TP-Rs in the brain stem was reduced by 50% with the addition of ANG II (P < 0.001) and during losartan administration was almost doubled by the LS diet (P < 0.001). The mRNA abundance for TxA(2)-S in the kidney cortex also was increased many times with the HS diet (P < 0.001). In contrast, the mRNA for TxA(2)-S in the brain was unaffected by salt. ANG II did not affect TxA(2)-S at either site. During losartan administration, TxA(2)-S increased modestly in the brain stem with the LS diet. mRNA abundance for TP-Rs in the kidney cortex and brain stem is suppressed by ANG II acting on AT(1)-Rs. In the absence of AT(1)-Rs, expression of TP-Rs at both sites is enhanced by LS intake. In contrast, ANG II does not affect the mRNA abundance for TxA(2)-S. Expression of TxA(2)-S is enhanced by HS intake in the kidney cortex but by LS intake in the brain stem only during losartan administration. Thus TP-Rs are strongly dependent on ANG II acting on AT(1)-Rs, whereas TxA(2)-S is regulated differentially in the kidney cortex and brain stem by salt intake.