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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Testosterone | Other | To determine the effect of testosterone on the NP responses to acute and chronic salt loading. One testosterone patch (Androderm 5 mg) applied to each male subject each day for 14 days. Intervention: Leuprolide acetate and anastrozole |
|
| Estradiol | Other | To determine the effect of estradiol on the NP responses to acute and chronic salt loading. Two estradiol patches (Vivelle Dot 0.1mg) will be applied to each female subject twice-a-week for 2 weeks. Intervention: leuprolide acetate |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| leuprolide acetate | Drug | Given to both arms to induce hypogonadism |
|
| Measure | Description | Time Frame |
|---|---|---|
| NP levels in men with testosterone patch and low-salt diet | B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP) | At day 7 of week of testosterone administration with low-salt diet |
| NP levels in men with testosterone patch and high-salt diet | B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP) | At day 7 of week of testosterone administration with high-salt diet |
| NP levels in women with estradiol patch and low-salt diet | B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP) | At day 7 of week of estradiol administration with low-salt diet |
| NP levels in women with estradiol patch and high-salt diet | B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP) | At day 7 of week of estradiol administration with high-salt diet |
| NP levels in men with placebo patch and low-salt diet | B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP) | At day 7 of week of placebo administration with low-salt diet |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Renin Activity (PRA) levels in women on estradiol on low-salt diet | Plasma Renin Activity (PRA) | At day 7 of week of estradiol administration on low-salt diet |
| Aldosterone levels in men with testosterone on low-salt diet |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Karen Miller, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D016729 | Leuprolide |
| D000077384 | Anastrozole |
| ID | Term |
|---|---|
| D007987 | Gonadotropin-Releasing Hormone |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
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| Anastrozole | Drug | Given to men to prevent conversion of administered testosterone to estradiol. |
|
|
| NP levels in men with placebo patch and high-salt diet | B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP) | At day 7 of week of placebo administration with high-salt diet |
| NP levels in women with placebo patch and low-salt diet | B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP) | At day 7 of week of placebo administration with low-salt diet |
| NP levels in women with placebo patch and high-salt diet | B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP) | At day 7 of week of placebo administration with high-salt diet |
Aldosterone
| At day 7 of week of testosterone administration on low-salt diet |
| Plasma Renin Activity (PRA) levels in women on estradiol on high-salt diet | Plasma Renin Activity (PRA) | At days 6 and 7 of week of estradiol administration on high-salt diet |
| Plasma Renin Activity (PRA) levels in women on placebo on low-salt diet | Plasma Renin Activity (PRA) | At day 7 of week of placebo administration on low-salt diet |
| Plasma Renin Activity (PRA) levels in women on placebo on high-salt diet | Plasma Renin Activity (PRA) | At days 6 and 7 of week of placebo administration on high-salt diet |
| Plasma Renin Activity (PRA) levels in men on testosterone on low-salt diet | At day 7 of week of testosterone administration on low-salt diet |
| Plasma Renin Activity (PRA) levels in men on testosterone on high-salt diet | At days 6 and 7 of week of testosterone administration on high-salt diet |
| Plasma Renin Activity (PRA) levels in men on placebo on low-salt diet | At day 7 of week of placebo administration on low-salt diet |
| Plasma Renin Activity (PRA) levels in men on placebo on high-salt diet | At days 6 and 7 of week of placebo administration on high-salt diet |
| Aldosterone levels in men on testosterone on high-salt diet | At days 6 and 7 of week of testosterone administration on high-salt diet |
| Aldosterone levels in men on placebo on high-salt diet | At days 6 and 7 of week of placebo administration on high-salt diet |
| Aldosterone levels in men on placebo on low-salt diet | At day 7 of week of placebo administration on low-salt diet |
| Aldosterone levels in women on estradiol on high-salt diet | At days 6 and 7 of week of estradiol administration on high-salt diet |
| Aldosterone levels in women on estradiol on low-salt diet | At day 7 of week of estradiol administration on low-salt diet |
| Aldosterone levels in women on placebo on high-salt diet | At days 6 and 7 of week of placebo administration on high-salt diet |
| Aldosterone levels in women on placebo on low-salt diet | At day 7 of week of placebo administration on low-salt diet |
| Urinary sodium concentration in women on estradiol on high-salt diet | 0, 60, and 120 minute of saline infusion on morning of day 7 of estradiol administration on high-salt diet |
| Urinary sodium concentration in women on placebo on high-salt diet | 0, 60, and 120 minute of saline infusion on morning of day 7 of placebo administration on high-salt diet |
| Urinary sodium concentration in men on testosterone on high-salt diet | 0, 60, and 120 minute of saline infusion on morning of day 7 of testosterone administration on high-salt diet |
| Urinary sodium concentration in men on placebo on high-salt diet | 0, 60, and 120 minute of saline infusion on morning of day 7 of placebo administration on high-salt diet |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |