Expression of mRNA of the GABA_A-α1 and NMDAR1 receptor subunits in the paraventricular nucleus of renal wrap hypertensive rats

Inhibition of GABA_A receptor function in the PVN results in an activation of the sympathetic nervous system. In one-kidney, figure-8 renal hypertensive rats, this effect is significantly attenuated. The goal of the present study was to determine if the expression of the mRNA for the GABA_A- α1-receptor subunit is altered in renal wrap hypertension. Rats were subjected to renal wrap (n=9) or unilateral nephrectomy (n=6). Four weeks later, arterial pressure was measured while conscious. The brains were removed, micropunches were taken of the paraventricular nucleus (PVN) region, and total RNA was isolated. The expression of GABA_A- α1 and the NMDAR1 subunits was determined with quantitative competitive RT-PCR using an internal standard of a shortened length (by about 60-100 bp) of the same sequence of target message, which was 304 bp of the GABA_A- α1 and 368 bp of the NMDAR1. The difference in the expression of the mRNAs was measured as a mass ratio between the target message to that of internal standard. Renal wrap animals had higher arterial pressure (134±4 vs 116±2 mmHg). The mass ratio of the GABA_A- α1 subunit was significantly reduced in hypertensive rats (5.3±1.1 vs 16.7±3.4) while the NMDAR1 subunit was not different (0.9±01 vs 0.7±0.2). The reduction in the expression of the GABA_A- α1 subunit in the PVN of renal wrapped hypertensive rats suggests a change in the subunit composition or number of GABA_A receptors. This alteration in the GABA_A receptor may contribute to the reduced PVN GABAergic inhibition on the sympathetic nervous system in hypertension.