Influence of circadian time and age on glomerular angiotensin II receptorsin normotensive Sprague-Dawley and transgenic hypertensive TGR(mREN2)27 rats

In male heterozygous transgenic hypertensive rats, TGR(mREN2)27 (TGR), exhi biting an inverse blood pressure profile and in normotensive Sprague-Dawley (SPRD) controls, the density and affinity of angiotensin II receptors were determined at six circadian times in glomeruli of animals 11 weeks old kep t under light-dark 12h:12 (LD 12:12) conditions. Angiotensin II receptors w ere also studied in rats 18-20 weeks old of both strains at 2h after light onset. As a measure of renal excretory functions, diuresis, creatinine, and protein excretion were monitored using metabolic cages. The expression of angiotensin II receptor mRNA was determined in renal arteries 2h-4h after l ight onset. The following results were obtained: (1) Renal excretory functi ons showed significant daily variation, with higher excretion rates in the dark span in both TGR and SPRD rats. (2) No circadian phase dependency was found in the glomerular angiotensin II receptors in both rat strains. Howev er, receptor density was significantly lower in TGR than in SPRD rats. In b oth strains, receptor number increased with aging. (3) In renal arteries, t he angiotensin II receptor mRNA of the main receptor subtype AT,, was neith er strain nor age dependent, AT(1B)- and AT(2)-receptor mRNAs were signific antly lower in TGR than SPRD rats. In conclusion, the results demonstrate t hat the overactive renin-angiotensin system in TGR rats led to a downregula tion of glomerular angiotensin II receptor:, that was not accompanied by a down-regulation of the mRNA of the dominant AT(1A)- receptor subtype. Circa dian short-term variations in blood pressure in both TGR and SPRD rats are not reflected by daily variation in angiotensin II receptor density of rena l glomeruli or by variation in receptor expression in renal vascular tissue .