Androgens augment proximal tubule transport.
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-Dawley 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 x min(-1) x 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.
Quan
Albert
A
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9063, USA.
Chakravarty
Sumana
S
Chen
Jian-Kang
JK
Chen
Jian-Chun
JC
Loleh
Samer
S
Saini
Neel
N
Harris
Ray C
RC
Capdevila
Jorge
J
Quigley
Raymond
R
D000042:Absorption / Q000187:drug effects; D000728:Androgens / Q000097:blood / Q000494:pharmacology*; D000804:Angiotensin II / Q000097:blood; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D013196:Dihydrotestosterone / Q000097:blood / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
D000728:Androgens; D012333:RNA, Messenger; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D013196:Dihydrotestosterone; D000808:Angiotensinogen; D000804:Angiotensin II; D013739:Testosterone