REGULATION OF PREPROTACHYKININ-A MESSENGER-RNA IN GENETIC HYPERTENSIVE AND NORMOTENSIVE RATS

It is well-known that central administration of tachykinins (Tks) inhi bit salt intake in rats. Recent studies have shown that conditions tha t arouse salt appetite, such as adrenalectomy and sodium depletion, in duce a decrease in preprotachykinin-A (PPT-A) mRNA in discrete regions of the rat brain, suggesting that reduced levels of PPT-A mRNA in the brain may have a permissive role on the expression of salt appetite. It has also been shown that spontaneously hypertensive rats (SHR) show higher avidity for salty solutions than their normotensive control Wi star-Kyoto (WKY) rats. In this regard, the present study tested whethe r SHR and WKY rats differ in expression of the gene coding for PPT-A, the precursor for Tks peptides. Using semi-quantitative in situ hybrid ization histochemistry, we examined the level of PPT-A mRNA in discret e rat brain regions of SHR and WKY rats under no treatment, after 1 or 3 days of Na+ depletion. Levels of PPT-A mRNA were analysed in the ol factory tubercle (Tu), in the lateral olfactory tubercle (LOT), in the dorsal and ventral caudate putamen (d/v CPu), in the medial preoptic area (mPOA), in the bed nucleus of the stria terminalis (BNST), in the habenula (Hb) and in the postero-dorsal part of the amygdala (MePD) S emi-quantitative analysis of silver grains revealed a 27.5% lower expr ession of the PPT-A mRNA levels in SHR opposite to WKY rats under no t reatment in v-CPu, mPOA, BNST and Hb. 1 day of Na+ depletion reduced P PT-A mRNA levels when opposite to Na+-repleted animals in Tu and mPOA in both SHR and WKY rats. On the other hand, when comparing SHR and WK Y rats after 1 day of Na+ depletion, a 26% lower level of PPT-A mRNA w as detected in Tu and d-CPu of SHR opposite to WKY rats whereas a 14% and an 18% lower level was detected in v-CPu and Hb, respectively. A l ower expression of PPT-A mRNA in SHR compared to WKY rats was also fou nd in BNST and MePD, although no statistical significance was detected in these two brain areas. In the last experiment, 3 days of Na+ deple tion reduced PPT-A mRNA levels in mPOA while negligibly increased mRNA levels in d-CPu and v-CPu, in BNST, Hb and MePD, both in SHR and WKY rats. Conversely, when making comparisons between the two strains, a 3 5% lower level of PPT-A mRNA in SHR with respect to WKY rats was found after 3 days of Na+ depletion in d-CPu, v-CPu and mPOA. A lower gene expression, even though not statistically significant, was found in Tu , LOT, MePD. These findings show a consistent difference of PPT-A mRNA levels in discrete regions of the SHR brain opposite to WKY rats and confirm that 1 day of Na+ depletion reduces PPT-A mRNA in discrete bra in regions. Since SHR are notoriously more salt-avid than WKY rats and Tks are potent inhibitors of sodium intake, the down-regulation of PP T-A mRNA may contribute to the higher natriophilia and, therefore, to the etiology of the hypertensive disease.