title: Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone.
abstract: Observational studies in primary hyperaldosteronism suggest a positive relationship between aldosterone and parathyroid hormone (PTH); however, interventions to better characterize the physiological relationship between the renin-angiotensin-aldosterone system (RAAS) and PTH are needed. We evaluated the effect of individual RAAS components on PTH using 4 interventions in humans without primary hyperaldosteronism. PTH was measured before and after study (1) low-dose angiotensin II (Ang II) infusion (1 ng/kg per minute) and captopril administration (25 mg×1); study (2) high-dose Ang II infusion (3 ng/kg per minute); study (3) blinded crossover randomization to aldosterone infusion (0.7 µg/kg per hour) and vehicle; and study (4) blinded randomization to spironolactone (50 mg/daily) or placebo for 6 weeks. Infusion of Ang II at 1 ng/kg per minute acutely increased aldosterone (+148%) and PTH (+10.3%), whereas Ang II at 3 ng/kg per minute induced larger incremental changes in aldosterone (+241%) and PTH (+36%; P<0.01). Captopril acutely decreased aldosterone (-12%) and PTH (-9.7%; P<0.01). In contrast, aldosterone infusion robustly raised serum aldosterone (+892%) without modifying PTH. However, spironolactone therapy during 6 weeks modestly lowered PTH when compared with placebo (P<0.05). In vitro studies revealed the presence of Ang II type I and mineralocorticoid receptor mRNA and protein expression in normal and adenomatous human parathyroid tissues. We observed novel pleiotropic relationships between RAAS components and the regulation of PTH in individuals without primary hyperaldosteronism: the acute modulation of PTH by the RAAS seems to be mediated by Ang II, whereas the long-term influence of the RAAS on PTH may involve aldosterone. Future studies to evaluate the impact of RAAS inhibitors in treating PTH-mediated disorders are warranted.
authors.affiliation: Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave, RFB, Boston, MA 02115. avaidya1@partners.org.
authors.forename: Jenifer M
authors.initials: JM
authors.lastname: Brown
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Williams
authors.forename: James M
authors.initials: JM
authors.lastname: Luther
authors.forename: Rajesh
authors.initials: R
authors.lastname: Garg
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Garza
authors.forename: Luminita H
authors.initials: LH
authors.lastname: Pojoga
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Ruan
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Williams
authors.forename: Gail K
authors.initials: GK
authors.lastname: Adler
authors.forename: Anand
authors.initials: A
authors.lastname: Vaidya
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000008:administration & dosage / Q000378:metabolism; D000804:Angiotensin II / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage; D002216:Captopril / Q000008:administration & dosage*; D004232:Diuretics / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000187:drug effects / Q000502:physiology; D010281:Parathyroid Hormone / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D013148:Spironolactone / Q000008:administration & dosage*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014807:Vitamin D / Q000097:blood
chemical_list: D000959:Antihypertensive Agents; D004232:Diuretics; D010281:Parathyroid Hormone; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D014807:Vitamin D; D013148:Spironolactone; D000450:Aldosterone; D002216:Captopril
keywords: aldosterone; calcium; parathyroid hormone; renin-angiotensin system; spironolactone; vitamin D