Gonadotropins in a female model of age-induced hypertension

Georgetown University, Washington DC

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Abstract

DESCRIPTION (provided by applicant): This project addresses the PA-10-015 by proposing to investigate the role and mechanisms of follicle stimulating hormone (FSH) and leutinizing hormone (LH) in the age-induced increase in blood pressure (BP) and body weight (BW) observed in the female Dahl salt-sensitive (DS) rat. We have previously shown that ovariectomy accelerates the age-induced increase in BP and BW in this model and that 172-estradiol (E2) prevents these effects. Aging and ovariectomy, however, also result in a marked rise in FSH and LH. Though some studies implicate these pituitary hormones in BP regulation, their mechanisms of action are poorly understood. These proposed studies will provide key insight into this experimental model of female aging and postmenopausal hypertension. Aim 1 will determine if preventing the rise in FSH & LH that occurs as a result of ovarian hormone deficiency during normal aging from 4 months old (mo) to 12 mo in the female DS rat will attenuate the age-associated increase in BP, BW, insulin insensitivity, endothelial dysfunction, renal oxidative stress and activation of the vasoconstrictor arm of the renin angiotensin system (RAS) in vascular, renal and adipose tissues. We will also investigate the E2 and progesterone (P4) dependency of these pituitary hormone effects. Aim 2 will serve as the corollary to Aim 1 and will determine if increasing FSH & LH in young (3-4 mo) female DS rats will result in an increase in BP, BW, insulin insensitivity, endothelial dysfunction, renal oxidative stress and activation of the vasoconstrictor arm of the RAS in vascular, renal and adipose tissues. The clinical significance of this research is the insight it will provide into the mechanisms underlying the marked rise in the prevalence of hypertension in women as they age and after their transition into menopause.