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| ANGIOTENSIN-II UP-REGULATES TYPE-1 ANGIOTENSIN-II RECEPTORS IN RENAL PROXIMAL TUBULE |
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| Author(s): CHENG HF, BECKER BN, BURNS KD, HARRIS RC |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 95 Issue: 5 Pages: 2012-2019 Published: MAY 1995 |
| Times Cited: 100 References: 38 |
| Abstract: Angiotensin II (Ang II) is an important regulator of proximal tubule salt and water reabsorption, Recent studies indicate that rabbit proximal tubule angiotensin II receptors are the type-1 (AT(1)R) subtype, We studied the effect of Ang II on proximal tubule receptor expression, Rabbits were treated with either angiotensin converting enzyme inhibitors or a low salt diet to modulate endogenous Ang II levels, In captopril-treated rabbits, liver and glomerular AT(1)R mRNA levels increased 242+/-125 and 141+/-60%, respectively (n = 6-7; P < 0.05), as determined by quantitative PCR, In contrast, proximal tubule AT(1)R mRNA levels decreased 40+/-11% (n = 6; P < 0.05), Binding of I-125 Ang II to renal cortical basolateral membranes of captopril-treated rabbits decreased from 2.9+/-0.55 to 1.4+/-0.17 fmol/mg protein (n = 6; P < 0.025), In rabbits fed a sodium chloride-deficient diet for 4 wk, AT(1)R mRNA levels decreased 52+/-11% in liver and 43+/-7% in glomeruli (n = 4-5; P < 0.05), whereas they increased 141+/-85% (n = 5; P < 0.05) in proximal tubule, In basolateral membranes from rabbits on the sodium chloride-deficient diet, specific binding of I-125 Ang II increased from 2.1+/-0.2 to 4.3+/-1.1 fmol/mg protein (n = 7; P < 0.05), To determine whether Ang II directly regulates expression of proximal tubule AT(1) receptors, further studies were performed in cultured proximal tubule cells grown from microdissected S1 segments of rabbit proximal tubules and immortalized by transfection with a replication-defective SV40 vector, Incubation of these cells with Ang n (10(-11) to 10(-7) M) led to concentration-dependent increases in both AT(1)R mRNA levels and specific I-125 Ang II binding, Pretreatment with pertussis toxin inhibited Ang II stimulation of AT(1)R mRNA, AT(1)R mRNA expression was decreased by either forskolin or a nonhydrolyzable cAMP analogue (dibutryl cAMP). Simultaneous Ang II administration overcame the inhibitory effect of forskolin but not dibutryl cAMP, These results indicate that proximal tubule AT(1)R expression is regulated by ambient Ang Il levels, and Ang II increases AT(1)R mRNA at least in part by decreasing proximal tubule cAMP generation through a pertussis toxin-sensitive mechanism, Upregulation of proximal tubule AT(1)R by Ang II may be important in mediating enhanced proximal tubule sodium reabsorption in states of elevated systemic or intrarenal Ang II. |
| Document Type: Article |
| Language: English |
Addresses:
1. VANDERBILT UNIV, SCH MED, DEPT MED, DIV NEPHROL, NASHVILLE, TN 37232 USA
2. DEPT VET AFFAIRS MED CTR, NASHVILLE, TN 37232 USA
3. UNIV OTTAWA, DEPT MED, OTTAWA, ON K1H 8M5 CANADA
4. UNIV OTTAWA, DEPT PHYSIOL, OTTAWA, ON K1H 8M5 CANADA |
| Publisher: ROCKEFELLER UNIV PRESS, 222 E 70TH STREET, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: QW205 |
| ISSN: 0021-9738 |
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