Abstract
The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawiey rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 ± 0.31 vs. 3.31 ± 0.23 nl·min -1·mm-1, P < 0.01). Luminally perfusing with either enalaprilat (10-4 M) to inhibit production of angiotensin II or losartan (10-8 M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.
| Original language | English (US) |
|---|---|
| Pages (from-to) | F452-F459 |
| Journal | American Journal of Physiology - Renal Physiology |
| Volume | 287 |
| Issue number | 3 56-3 |
| DOIs | |
| State | Published - Sep 1 2004 |
| Externally published | Yes |
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Keywords
- Dihydrotestosterone
- Microperfusion
- Renin-angiotensin
- Testosterone
ASJC Scopus subject areas
- Physiology
- Urology
Cite this
Androgens augment proximal tubule transport. / Quan, Albert; Chakravarty, Sumana; Chen, Jiankang; Chen, Jian Chun; Loleh, Samer; Saini, Neel; Harris, Ray C.; Capdevila, Jorge; Quigley, Raymond.
In: American Journal of Physiology - Renal Physiology, Vol. 287, No. 3 56-3, 01.09.2004, p. F452-F459.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Androgens augment proximal tubule transport
AU - Quan, Albert
AU - Chakravarty, Sumana
AU - Chen, Jiankang
AU - Chen, Jian Chun
AU - Loleh, Samer
AU - Saini, Neel
AU - Harris, Ray C.
AU - Capdevila, Jorge
AU - Quigley, Raymond
PY - 2004/9/1
Y1 - 2004/9/1
N2 - The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawiey rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 ± 0.31 vs. 3.31 ± 0.23 nl·min -1·mm-1, P < 0.01). Luminally perfusing with either enalaprilat (10-4 M) to inhibit production of angiotensin II or losartan (10-8 M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.
AB - The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawiey rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 ± 0.31 vs. 3.31 ± 0.23 nl·min -1·mm-1, P < 0.01). Luminally perfusing with either enalaprilat (10-4 M) to inhibit production of angiotensin II or losartan (10-8 M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.
KW - Dihydrotestosterone
KW - Microperfusion
KW - Renin-angiotensin
KW - Testosterone
UR - http://www.scopus.com/inward/record.url?scp=4143059004&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4143059004&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00188.2003
DO - 10.1152/ajprenal.00188.2003
M3 - Article
C2 - 15100096
AN - SCOPUS:4143059004
VL - 287
SP - F452-F459
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 3 56-3
ER -