Study of the Effect of Testosterone and Estradiol on NP Responses to Acute and Chronic Salt Loading

Gonadal Steroid Regulation of the Natriuretic Peptide System

There is gender dimorphism in cardiovascular risk, with men at higher risk than women. However, the fundamental basis for the protective effect of female sex remains unclear. Recent data implicate the natriuretic peptide (NP) system as an important determinant of blood pressure. Also, NP levels are twice as high in women of reproductive age than in men, and gonadal steroids are important determinants of circulating NPs. These are the marked, but poorly understood differences in the NP status between men and women. The investigators hypothesize that gonadal steroids regulate NP release, specifically that testosterone inhibits and estrogen activates the NP axis, leading to differences in both resting NP levels and dynamic responses of the NP, RAAS, and kidneys to acute and chronic salt loading. Understanding the basis for gender differences in NP function should provide important insights regarding mechanisms underlying hypertension in men versus women.

Inclusion Criteria:

• 18-40 years old
• no history of hypertension
• normal BMI
• Male: normal testosterone and free testosterone levels
• Female: regular menses, negative pregnancy test, no sex steroid therapy >/=3 mos

Exclusion Criteria:

• on hypertensives, diuretics, or insulin
• with diabetes mellitus
• estimated creatinine clearance <60 ml/min
• prior cardiovascular, liver or renal disease
• history of hormonally-responsive cancer
• elevated liver function test (LFTs)
• atrial fibrillation
• abnormal sodium or potassium levels
• taking medications that directly impact the endocrine system (exogenous hormones, steroids, etc.)
• taking medications that indirectly impact the endocrine system (SSRIs, opioids, finasteride, etc.)
• with untreated hyper- or hypothyroidism
• smoker
• psychiatric history
• Women: not willing to abstain from getting pregnant during the course of the study, with abnormal menstrual cycle, or who have osteoporosis
• Men: with polycythemia