Testosterone-dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats.
Blood pressure (BP) is more salt sensitive in men than in premenopausal women. In Dahl salt-sensitive rats (DS), high-salt (HS) diet increases BP more in males than females. In contrast to the systemic renin-angiotensin system, which is suppressed in response to HS in male DS, intrarenal angiotensinogen expression is increased, and intrarenal levels of ANG II are not suppressed. In this study, the hypothesis was tested that there is a sexual dimorphism in HS-induced upregulation of intrarenal angiotensinogen mediated by testosterone that also causes increases in BP and renal injury. On a low-salt (LS) diet, male DS had higher levels of intrarenal angiotensinogen mRNA than females. HS diet for 4 wk increased renal cortical angiotensinogen mRNA and protein only in male DS, which was prevented by castration. Ovariectomy of female DS had no effect on intrarenal angiotensinogen expression on either diet. Radiotelemetric BP was similar between males and castrated rats on LS diet. HS diet for 4 wk caused a progressive increase in BP, protein and albumin excretion, and glomerular sclerosis in male DS rats, which were attenuated by castration. Testosterone replacement in castrated DS rats increased BP, renal injury, and upregulation of renal angiotensinogen associated with HS diet. Testosterone contributes to the development of hypertension and renal injury in male DS rats on HS diet possibly through upregulation of the intrarenal renin-angiotensin system.
Yanes
Licy L
LL
Univ. of Mississippi Medical Center, Dept. of Physiology and Biophysics, 2500 N. State St., Jackson, MS 39216-4505, USA. lyanes@physiology.umsmed.edu
Sartori-Valinotti
Julio C
JC
Iliescu
Radu
R
Romero
Damian G
DG
Racusen
Lorraine C
LC
Zhang
Huimin
H
Reckelhoff
Jane F
JF
D000419:Albuminuria / Q000209:etiology / Q000378:metabolism; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D004195:Disease Models, Animal; D004343:Drug Implants; D004958:Estradiol / Q000097:blood; D005260:Female; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System; D012737:Sex Factors; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D013686:Telemetry; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D004343:Drug Implants; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D017673:Sodium Chloride, Dietary; D000808:Angiotensinogen; D013739:Testosterone; D004958:Estradiol