Sexual dimorphism in urinary angiotensinogen excretion during chronic angiotensin II-salt hypertension.
BACKGROUND
The intrarenal renin-angiotensin system contributes to hypertension by regulating sodium and water reabsorption throughout the nephron. Sex differences in the intrarenal components of the renin-angiotensin system have been involved in the greater incidence of high blood pressure and progression to kidney damage in males than females.


OBJECTIVE
This study investigated whether there is a sex difference in the intrarenal gene expression and urinary excretion of angiotensinogen (AGT) during angiotensin II (Ang II)-dependent hypertension and high-salt (HS) diet.


METHODS
Male and female Sprague-Dawley rats were divided into 5 groups for each sex: Normal-salt control, HS diet (8% NaCl), Ang II-infused (80 ng/min), Ang II-infused plus HS diet, and Ang II-infused plus HS diet and treatment with the Ang II receptor blocker, candesartan (25 mg/L in the drinking water). Rats were evaluated for systolic blood pressure (SBP), kidney AGT mRNA expression, urinary AGT excretion, and proteinuria at different time points during a 14-day protocol.


RESULTS
Both male and female rats exhibited similar increases in urinary AGT, with increases in SBP during chronic Ang II infusion. HS diet greatly exacerbated the urinary AGT excretion in Ang II-infused rats; males had a 9-fold increase over Ang II alone and females had a 2.5-fold increase. Male rats displayed salt-sensitive SBP increases during Ang II infusion and HS diet, and female rats did not. In the kidney cortex, males displayed greater AGT gene expression than females during all treatments. During Ang II infusion, both sexes exhibited increases in AGT gene message compared with same-sex controls. In addition, HS diet combined with Ang II infusion exacerbated the proteinuria in both sexes. Concomitant Ang II receptor blocker treatment during Ang II infusion and HS diet decreased SBP and urinary AGT similarly in both sexes; however, the decrease in proteinuria was greater in the females.


CONCLUSIONS
During Ang II-dependent hypertension and HS diet, higher intrarenal renin-angiotensin system activation in males, as reflected by higher AGT gene expression and urinary excretion, indicates a mechanism for greater progression of high blood pressure and might explain the sex disparity in development of salt-sensitive hypertension.
Department of Physiology, School of Medicine, Tulane University, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Vicky F
VF
Rands
Dale M
DM
Seth
Hiroyuki
H
Kobori
Minolfa C
MC
Prieto
D000804:Angiotensin II / Q000378:metabolism*; D000808:Angiotensinogen / Q000652:urine*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D012737:Sex Factors; D017673:Sodium Chloride, Dietary
D017673:Sodium Chloride, Dietary; D000808:Angiotensinogen; D000804:Angiotensin II