Helle A Praetorius | PubMed Health

PubMed2006

Angiotensin II mediates downregulation of aquaporin water channels and key renal sodium transporters in response to urinary tract obstruction.

The renin-angiotensin system is well known to be involved in the pathophysiological changes in renal function after obstruction of the ureter. Previously, we demonstrated that bilateral ureteral obstruction (BUO) is associated with dramatic changes in the expression of both renal sodium transporters and aquaporin water channels (AQPs). We now examined the effects of the AT(1)-receptor antagonist candesartan on the dysregulation of AQPs and key renal sodium transporters in rats subjected to 24-h BUO and followed 2 days after release of BUO (BUO-2R). Consistent with previous observations, BUO-2R resulted in a significantly decreased expression of AQP1, -2, and -3 compared with control rats. Concomitantly, the rats developed polyuria and reduced urine osmolality. Moreover, expression of the type 2 Na-phosphate cotransporter (NaPi-2) and type 1 bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) was markedly reduced, consistent with postobstructive natriuresis. Candesartan treatment from the onset of obstruction attenuated the reduction in GFR (3.1 +/- 0.4 vs. 1.7 +/- 0.3 ml.min(-1).kg(-1)) and partially prevented the reduction in the expression of AQP2 (66 +/- 21 vs. 13 +/- 2%, n = 7; P < 0.05), NaPi-2 (84 +/- 6 vs. 57 +/- 10%, n = 7; P < 0.05), and NKCC2 (89 +/- 12 vs. 46% +/- 11, n = 7; P < 0.05). Consistent with this, candesartan treatment attenuated the increase in urine output (58 +/- 4 vs. 97 +/- 5 microl.min(-1).kg(-1), n = 7; P < 0.01) and the reduction in sodium reabsorption (433 +/- 62 vs. 233 +/- 45 micromol.min(-1).kg(-1), n = 7; P < 0.05) normally found in rats subjected to BUO. Moreover, candesartan treatment attenuated induction of cyclooxygenase 2 (COX-2) expression in the inner medulla, suggesting that COX-2 induction in response to obstruction is regulated by ANG II. In conclusion, candesartan prevents dysregulation of AQP2, sodium transporters, and development of polyuria seen in BUO. This strongly supports the view that candesartan protects kidney function in response to urinary tract obstruction.

Angiotensin II↗

PubMed2005

A physiological view of the primary cilium.

The primary cilium, an organelle largely ignored by physiologists, functions both as a mechano-sensor and a chemo-sensor in renal tubular epithelia. This forgotten structure is critically involved in the determination of left-right sidedness during development and is a key factor in the development of polycystic kidney disease, as well as a number of other abnormalities. This review provides an update of our current understanding about the function of primary cilia. Much new information obtained in the past five years has been stimulated, in part, by discoveries of the primary cilium's key role in the genesis of polycystic kidney disease as well as its involvement in determination of left-right axis asymmetry. Here we focus on the various functions of the primary cilium rather than on its role in pathology.

Animals↗

PubMed2003

The renal cell primary cilium functions as a flow sensor.

PURPOSE OF REVIEW: To discuss recent reports on the function and importance of the renal primary cilium, a widely distributed organelle. RECENT FINDINGS: Most epithelial cells, including those in the kidney, express a solitary primary cilium. The primary cilium functions as a flow sensor in cultured renal epithelial cells (MDCK and mouse collecting tubule) mediating a large increase in intracellular calcium concentration. Flow sensing is shown to reside in the cilium itself and to involve the proteins polycystin 1 and 2, defects in which are associated with the majority of cases of human polycystic kidney disease. The role of the cilium in flow-dependent potassium secretion by the collecting tubule and in sensing of chemical components of the luminal fluid are also described. SUMMARY: The primary cilium is mechanically sensitive and serves as a flow sensor in cultured renal epithelia. Bending the cilium by mechanical means or flow causes a large, prolonged transient increase in intracellular calcium. The mechanically sensitive protein in the cilium is a polycystin.

Animals↗