DISTINCT MECHANISMS OF UP-REGULATION OF TYPE 1A ANGIOTENSIN-II RECEPTOR GENE-EXPRESSION IN KIDNEY AND ADRENAL-GLAND

We previously demonstrated that type 1A angiotensin II (Ang II) receptor (AT(1A)) is the predominant renal subtype and is upregulated by a low sodium diet. We have now tested the hypothesis that upregulation of AT(1A) mRNA induced by sodium deficiency is renal specific and is mediated by activation of type 1 Ang II receptor (AT(1)). Male Wistar rats were divided into four groups (n=5 each) and treated for 2 weeks with normal sodium diet (0.5%), normal sodium plus 3 mg/kg per day losartan, low sodium diet (0.07%), or low sodium diet plus losartan. At the end of the 2 weeks, body weight and mean arterial pressure were not different among the four groups (P>.05). Plasma renin activity was elevated by losartan treatment, sodium restriction, or the combination of the two versus control (P<.05). Northern blot analysis showed that the ratio of renal AT(1A) to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA was increased by losartan treatment, sodium restriction, or the combination of the two versus control (P<.05). In contrast, the ratio of adrenal AT(1A) to GAPDH mRNA was increased only by sodium restriction versus three other groups (P<.05). Thus, sodium deficiency increases AT(1A) mRNA in both kidney and adrenal gland, while Ang II receptor blockade by losartan pre vents low sodium-induced AT(1A) mRNA only in adrenal gland. We conclude that the increase in AT(1A) mRNA induced by sodium deficiency is not renal specific and that different mechanisms of regulation exist, ie, in adrenal gland, low sodium-induced upregulation of AT(1A) is dependent upon Ang II activation of the AT(1) receptor, while in kidney, a non-AT(1)-dependent mechanism is operant.