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

Abstract

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 A2 synthase (TxA2-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 AT1 receptor (AT1-R) antagonist losartan. Excretion of thromboxane B2 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 β-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 TxA2-S in the kidney cortex also was increased many times with the HS diet ( P < 0.001). In contrast, the mRNA for TxA2-S in the brain was unaffected by salt. ANG II did not affect TxA2-S at either site. During losartan administration, TxA2-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 AT1-Rs. In the absence of AT1-Rs, expression of TP-Rs at both sites is enhanced by LS intake. In contrast, ANG II does not affect the mRNA abundance for TxA2-S. Expression of TxA2-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 AT1-Rs, whereas TxA2-S is regulated differentially in the kidney cortex and brain stem by salt intake.