Gender and susceptibility to kidney damage in high BP

Summary

Principal Investigator: JANE RECKELHOFF
Abstract: DESCRIPTION (provided by applicant): The use of androgen supplements is becoming increasingly prevalent in the United States mainly in the general population of middle-aged and elderly men with chronic cardiovascular diseases, such as hypertension and type II diabetes, who receive testosterone supplements to treat osteoporosis, improve libido and feelings of well-being, and to improve sexual performance. Despite the common use of androgens, the long term impact of androgen supplements in healthy individuals, much less in individuals who suffer from chronic cardiovascular-renal diseases (CV-RD), is unknown. Recent studies from our laboratory and others indicate that endogenous androgens contribute to greater renal injury in normotensive and hypertensive male rats. However, there is little information regarding whether androgen supplements exacerbate renal injury and by what mechanisms. The overall hypothesis to be tested in this proposal is that androgen supplements exacerbate renal injury by directly increasing oxidative stress via NADPH oxidase, and hemodynamically by increasing transmission of pressure to the glomerulus. We further hypothesize that androgen supplements indirectly increase ROS by stimulating the RAS. Finally, the hypothesis will be tested that androgen supplements could activate NF-DB in the kidney promoting inflammation. In humans the two leading causes for renal injury are hypertension and type II diabetes. Therefore, studies will be performed in male rat models that mimic men who suffer from CV-RD and are prescribed androgen supplements: men with hypertensive renal injury (rats with reduced renal mass on high salt diet), and men with type II diabetes (Zucker rats), using testosterone, the most commonly prescribed androgen for men. Studies will also be performed in human male mesangial cells. The specific aims of the proposal are to test the hypotheses that: 1) androgen supplements will exacerbate renal injury in rats with hypertension or type II diabetes;2) androgen supplements will exacerbate renal injury by increasing oxidative stress mediated by NADPH oxidase and that the intrarenal RAS plays a role in mediating androgen supplement-induced oxidative stress;3) androgen supplements will exacerbate renal injury by activating NF-DB leading to increased inflammatory cytokines;4) androgen supplements will exacerbate renal injury by increasing transmission of pressure to the glomerulus.
Funding Period: ----------------2001 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. ncbi Role of the renal nerves in blood pressure in male and female SHR
    Radu Iliescu
    Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216 4505, USA
    Am J Physiol Regul Integr Comp Physiol 290:R341-4. 2006
  2. pmc Protective role of testosterone in ischemia-reperfusion-induced acute kidney injury
    Andrea Soljancic
    Department of Medicine, Division of Nephrology, University of Mississippi Medical Center, Jackson, MS 39216, USA
    Am J Physiol Regul Integr Comp Physiol 304:R951-8. 2013
  3. ncbi Sex and gender differences in control of blood pressure
    Rodrigo Marañón
    Women s Health Research Center and Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216 4505, USA
    Clin Sci (Lond) 125:311-8. 2013
  4. pmc Sex differences in control of blood pressure: role of oxidative stress in hypertension in females
    Arnaldo Lopez-Ruiz
    Dept of Physiology and Biophysics, Univ of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216 4505, USA
    Am J Physiol Heart Circ Physiol 295:H466-74. 2008
  5. doi Sex and sex steroids in cardiovascular-renal physiology and pathophysiology
    Jane F Reckelhoff
    Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216 4505, USA
    Gend Med 5:S1-2. 2008
  6. doi Sex and the kidney
    Radu Iliescu
    Hypertension 51:1000-1. 2008
  7. doi Menopause and hypertension: an age-old debate
    Megan Coylewright
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Hypertension 51:952-9. 2008
  8. doi Sex steroids and renal disease: lessons from animal studies
    Licy L Yanes
    Department of Physiology and Biophysics, The Center for Excellence in Cardiovascular Renal Research, University of Mississippi Medical Center, Jackson, MS 39216 4505, USA
    Hypertension 51:976-81. 2008
  9. ncbi Sex differences in the pressor response to angiotensin II when the endogenous renin-angiotensin system is blocked
    Julio C Sartori-Valinotti
    Department of Physiology and Biophysics, The Center for Excellence in Cardiovascular Renal Research, University of Mississippi Medical Center, Jackson, MS 39216 4505, USA
    Hypertension 51:1170-6. 2008
  10. ncbi Sex differences in oxidative stress and the impact on blood pressure control and cardiovascular disease
    Julio C Sartori-Valinotti
    Department of Physiology and Biophysics and The Center of Excellence in Cardiovascular Renal Research, University of Mississippi Medical Center, Jackson, Mississippi 39216 4504, USA
    Clin Exp Pharmacol Physiol 34:938-45. 2007

Scientific Experts

  • Licy L Yanes
  • Roberta Lima
  • Jane F Reckelhoff
  • Radu Iliescu
  • Julio C Sartori-Valinotti
  • Rodrigo Marañón
  • Mohadetheh Moulana
  • Andrea Soljancic
  • Arnaldo Lopez Ruiz
  • Deborah D Davis
  • Jing Li
  • Lorraine C Racusen
  • Arnaldo F Lopez-Ruiz
  • Michael J Ryan
  • Marcia Venegas-Pont
  • Arnaldo Lopez-Ruiz
  • Megan Coylewright
  • Luis A Juncos
  • Kiran Chandrashekar
  • Ruisheng Liu
  • Kuichang Yuan
  • Babbette LaMarca
  • Allison V Jones
  • Porter H Glover
  • Marcia R Venegas-Pont
  • Damian G Romero
  • Babbette B LaMarca
  • Wanda Dorsett-Martin
  • Julio Sartori-Valinotti
  • Pamela Ouyang
  • Valeria E Cucchiarelli
  • Lourdes A Fortepiani
  • Joshua W Iles
  • William Bell
  • Ovidiu C Baltatu
  • Terry Dwyer

Detail Information

Publications30

  1. ncbi Role of the renal nerves in blood pressure in male and female SHR
    Radu Iliescu
    Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216 4505, USA
    Am J Physiol Regul Integr Comp Physiol 290:R341-4. 2006
    ..These data indicate that renal nerves play a role in the control of blood pressure in SHR independent of sex, but do not play a role in mediating the sex differences in blood pressure...
  2. pmc Protective role of testosterone in ischemia-reperfusion-induced acute kidney injury
    Andrea Soljancic
    Department of Medicine, Division of Nephrology, University of Mississippi Medical Center, Jackson, MS 39216, USA
    Am J Physiol Regul Integr Comp Physiol 304:R951-8. 2013
    ....
  3. ncbi Sex and gender differences in control of blood pressure
    Rodrigo Marañón
    Women s Health Research Center and Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216 4505, USA
    Clin Sci (Lond) 125:311-8. 2013
    ..In the present review, the roles of sex steroids and gender in mediating or protecting against hypertension and cardiovascular disease will be discussed...
  4. pmc Sex differences in control of blood pressure: role of oxidative stress in hypertension in females
    Arnaldo Lopez-Ruiz
    Dept of Physiology and Biophysics, Univ of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216 4505, USA
    Am J Physiol Heart Circ Physiol 295:H466-74. 2008
    ..As such, future clinical trials should be designed and powered to evaluate the effects of oxidative stress on blood pressure separately in men and women...
  5. doi Sex and sex steroids in cardiovascular-renal physiology and pathophysiology
    Jane F Reckelhoff
    Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216 4505, USA
    Gend Med 5:S1-2. 2008
  6. doi Sex and the kidney
    Radu Iliescu
    Hypertension 51:1000-1. 2008
  7. doi Menopause and hypertension: an age-old debate
    Megan Coylewright
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Hypertension 51:952-9. 2008
  8. doi Sex steroids and renal disease: lessons from animal studies
    Licy L Yanes
    Department of Physiology and Biophysics, The Center for Excellence in Cardiovascular Renal Research, University of Mississippi Medical Center, Jackson, MS 39216 4505, USA
    Hypertension 51:976-81. 2008
  9. ncbi Sex differences in the pressor response to angiotensin II when the endogenous renin-angiotensin system is blocked
    Julio C Sartori-Valinotti
    Department of Physiology and Biophysics, The Center for Excellence in Cardiovascular Renal Research, University of Mississippi Medical Center, Jackson, MS 39216 4505, USA
    Hypertension 51:1170-6. 2008
    ..With ACEI, MAP in females on normal salt is more responsive to Ang II but is independent of oxidative stress or renal injury. MAP in males is salt-sensitive with Ang II, which may be mediated by oxidative stress and renal injury...
  10. ncbi Sex differences in oxidative stress and the impact on blood pressure control and cardiovascular disease
    Julio C Sartori-Valinotti
    Department of Physiology and Biophysics and The Center of Excellence in Cardiovascular Renal Research, University of Mississippi Medical Center, Jackson, Mississippi 39216 4504, USA
    Clin Exp Pharmacol Physiol 34:938-45. 2007
    ..Furthermore, anti-oxidant therapy in humans often does not ameliorate, or even attenuate, the negative cardiovascular consequences of increased oxidative stress. Our studies in SHR shed light on why these outcomes occur...
  11. ncbi Impact of androgen-induced oxidative stress on hypertension in male SHR
    Radu Iliescu
    Department of Physiology and Biophysics, The Center for Excellence in Cardiovascular Renal Research, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216 4505, USA
    Am J Physiol Regul Integr Comp Physiol 292:R731-5. 2007
    ..These data support the hypothesis that androgens cause oxidative stress and thereby increase blood pressure in male SHR via an NADPH oxidase-dependent mechanism...
  12. ncbi Cardiovascular disease, estrogen deficiency, and inflammatory cytokines
    Jane F Reckelhoff
    Hypertension 48:372-3. 2006
  13. ncbi Sexual dimorphism in the renin-angiotensin system in aging spontaneously hypertensive rats
    Licy L Yanes
    Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216 4505, USA
    Am J Physiol Regul Integr Comp Physiol 291:R383-90. 2006
    ....
  14. pmc Postmenopausal hypertension
    Licy L Yanes
    Women s Health Research Center, University of Mississippi Medical Center, Jackson, Mississippi, USA
    Am J Hypertens 24:740-9. 2011
    ....
  15. pmc Cardiovascular-renal and metabolic characterization of a rat model of polycystic ovary syndrome
    Licy L Yanes
    Women s Health Research Center, Center of Excellence in Cardiovascular Renal Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216 4505, USA
    Gend Med 8:103-15. 2011
    ..Hypertension, a common finding in women with PCOS, is a leading risk factor for cardiovascular disease. The mechanisms responsible for hypertension in women with PCOS have not been elucidated...
  16. pmc Testosterone supplementation in male obese Zucker rats reduces body weight and improves insulin sensitivity but increases blood pressure
    Deborah D Davis
    Women s Health Research Center, Department of Physiology, University of Mississippi Medical Center, Jackson, MS 39216 4505, USA
    Hypertension 59:726-31. 2012
    ..Testosterone supplements increased proteinuria and accelerated renal injury in lean Zucker rats only. Thus, treatment of obese men with chronic testosterone supplements should be done with careful monitoring of blood pressure...
  17. pmc Hypertension in postmenopausal women
    Roberta Lima
    Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216 4505, USA
    Curr Hypertens Rep 14:254-60. 2012
    ..This review describes possible mechanisms by which blood pressure may be increased in postmenopausal women...
  18. pmc A model of preeclampsia in rats: the reduced uterine perfusion pressure (RUPP) model
    Jing Li
    Women s Health Research Center, Jackson, Mississippi, USA
    Am J Physiol Heart Circ Physiol 303:H1-8. 2012
    ..This review discusses these features...
  19. pmc Postmenopausal hypertension: role of 20-HETE
    Licy L Yanes
    Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, 39216 4505, USA
    Am J Physiol Regul Integr Comp Physiol 300:R1543-8. 2011
    ..The data also suggest that cerebral production of 20-HETE may be increased and renal tubular production may be decreased in PMR, thus both contributing to their elevated BP...
  20. pmc A single pill to treat postmenopausal hypertension? Not yet
    Licy L Yanes
    Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216 4505, USA
    Curr Top Med Chem 11:1736-41. 2011
    ..A clear understanding of the complex pathogenesis of postmenopausal hypertension is needed in order to offer the best therapeutic options for these women...
  21. pmc Metabolic syndrome, androgens, and hypertension
    Mohadetheh Moulana
    Women s Health Research Center, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216 4505, USA
    Curr Hypertens Rep 13:158-62. 2011
    ..This review discusses the possibility that the effects of androgens on metabolic syndrome and its sequelae may differ between males and females...
  22. pmc Postmenopausal hypertension: role of the Renin-Angiotensin system
    Licy L Yanes
    Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216 4505, USA
    Hypertension 56:359-63. 2010
    ..The data suggest that other mechanisms besides activation of the RAS are likely involved in postmenopausal hypertension...
  23. pmc Sexual dimorphism in the blood pressure response to angiotensin II in mice after angiotensin-converting enzyme blockade
    Marcia Venegas-Pont
    Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA
    Am J Hypertens 23:92-6. 2010
    ..We tested whether female mice exhibit a greater MAP response to chronic Ang II during ACE inhibition...
  24. pmc Rosiglitazone reduces blood pressure in female Dahl salt-sensitive rats
    Julio C Sartori-Valinotti
    Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216 4505, United States
    Steroids 75:794-9. 2010
    ..In summary, PPARgamma activation reduces BP in INT and OVX females, but attenuates the salt sensitivity of BP in OVX only, likely due to increases in NO and in part to reductions in renal resident macrophages and inflammation...
  25. pmc Testosterone-dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats
    Licy L Yanes
    Univ of Mississippi Medical Center, Dept of Physiology and Biophysics, 2500 N State St, Jackson, MS 39216 4505, USA
    Am J Physiol Renal Physiol 296:F771-9. 2009
    ..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...
  26. pmc Refractory blood pressure in female SHR to increased oxidative stress is not mediated by NO or by upregulation of renal antioxidant enzymes
    Arnaldo F Lopez-Ruiz
    Dept of Physiology and Biophysics, Univ of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216 4505, USA
    Am J Physiol Regul Integr Comp Physiol 298:R266-71. 2010
    ....