Collecting duct renin is upregulated in both kidneys of 2-kidney, 1-clip Goldblatt hypertensive rats

Renin in collecting duct cells is upregulated in chronic angiotensin II-infused rats via angiotensin II type 1 receptors. To determine whether stimulation of collecting duct renin is a blood pressure-dependent effect; changes in collecting duct renin and associated parameters were assessed in both kidneys of 2-kidney, 1-clip Goldblatt hypertensive (2K1C) rats. Renal medullary tissues were used to avoid the contribution of renin from juxtaglomerular cells. Systolic blood pressure increased to 184 +/- 9 mm Hg in 2K1C rats (n=19) compared with sham rats (121 +/- 6 mm Hg; n=12). Although renin immunoreactivity markedly decreased in juxtaglomerular cells of nonclipped kidneys (NCK: 0.2 +/- 0.0 versus 1.0 +/- 0.0 relative ratio) and was augmented in clipped kidneys (CK: 1.7 +/- 1.0 versus 1.0 +/- 0.0 relative ratio), its immunoreactivity increased in cortical and medullary collecting ducts of both kidneys of 2K1C rats (CK: 2.8 +/- 1.0 cortex; 2.1 +/- 1.0 medulla; NCK: 4.6 +/- 2.0 cortex, 3.2 +/- 1.0 medulla versus 1.0 +/- 0.0 in sham kidneys). Renal medullary tissues of 2K1C rats showed greater levels of renin protein (CK: 1.4 +/- 0.2; NCK: 1.5 +/- 0.3), renin mRNA (CK: 5.8 +/- 2.0; NCK: 4.9 +/- 2.0), angiotensin I (CK: 120 +/- 18 pg/g; NCK: 129 +/- 13 pg/g versus sham: 67 +/- 6 pg/g), angiotensin II (CK: 150 +/- 32 pg/g; NCK: 123 +/- 21 pg/g versus sham: 91 +/- 12 pg/g; P < 0.05), and renin activity (CK: 8.6 mu g of angiotensin I per microgram of protein; NCK: 8.3 mu g of angiotensin I per microgram of protein; sham: 3.4 mu g of angiotensin I per microgram of protein) than sham rats. These data indicate that enhanced collecting duct renin in 2K1C rats occurs independently of blood pressure. Upregulation of distal tubular renin helps to explain how sustained intrarenal angiotensin II formation occurs even during juxtaglomerular renin suppression, thus allowing maintained effects on tubular sodium reabsorption that contribute to the hypertension.