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Interrelationships between the renin-angiotensin-aldosterone and calcium homeostatic systems
F D Grant1, S J Mandel, E M Brown
1Endocrine-Hypertension Division, Brigham & Women's Hospital, Boston, Massachusetts 02115.
Insights
This study investigated the interaction between angiotensin II (AII) and human parathyroid hormone (hPTH(1-34)) in regulating blood pressure. Results show these hormones have antagonistic effects on calcium and sodium homeostasis, suggesting a shared mechanism in blood pressure control.
Area of Science:
- Endocrinology
- Nephrology
- Cardiovascular Physiology
Background:
- Blood pressure regulation involves complex interactions between hormonal systems.
- Sodium and calcium intake significantly impact blood pressure.
- Understanding the interplay between hormonal regulators of sodium and calcium is crucial for managing hypertension.
Purpose of the Study:
- To investigate the potential interaction between angiotensin II (AII) and human parathyroid hormone (hPTH(1-34)) regulatory mechanisms.
- To explore how AII and hPTH(1-34) influence calcium and sodium homeostasis.
- To elucidate the combined effects of AII and hPTH(1-34) on blood pressure regulation.
Main Methods:
- Eight healthy male volunteers participated in a controlled study.
- Infusions of AII, hPTH(1-34), and a combination of both were administered over one hour on separate occasions.
- Blood samples and urine were collected at regular intervals to measure hormone levels, serum ionized calcium, phosphate, cAMP, and plasma renin activity (PRA).
Main Results:
- Angiotensin II infusion increased intact parathyroid hormone (PTH) and decreased serum ionized calcium.
- hPTH(1-34) infusion increased N-terminal PTH, decreased phosphate reabsorption, increased urinary cAMP, suppressed endogenous PTH, and elevated PRA without altering serum ionized calcium.
- Co-infusion of AII and hPTH(1-34) resulted in antagonistic effects, with minimal changes in serum ionized calcium, intact PTH, or PRA.
Conclusions:
- Angiotensin II and hPTH(1-34) exhibit antagonistic interactions in regulating calcium and sodium homeostasis.
- These findings suggest a shared mechanism underlying the association between calcium, sodium, and blood pressure regulation.
- The study highlights the complex interplay of hormonal systems in maintaining cardiovascular health.
Abstract:
Blood pressure is affected by both sodium and calcium intake. To determine if there is an interaction between the regulatory mechanisms for these two cations, eight normal male volunteers received the following 1-h infusions on three different days: 1) angiotensin II (AII), 2) the synthetic 1-34 amino terminal fragment of human PTH [hPTH(1-34)], and 3) AII and hPTH(1-34) together. Blood samples were obtained at t = 0 and every 20 min during each infusion and urine was collected for 3 h both before and after the start of each infusion. Infusion of AII produced an increase in intact PTH from 18 +/- 2 to 31 +/- 4 ng/L (P < 0.05), most likely in response to a small decrease in serum ionized calcium (1.25 +/- 0.01 to 1.23 +/- 0.01 mmol/L, P < 0.05). Urinary excretion of calcium was unchanged. Infusion of hPTH(1-34) at 200 U/h increased N-terminal PTH levels (18 +/- 3 to 268 +/- 42 ng/L, P < 0.05), decreased tubular reabsorption of phosphate (0.92 +/- 0.03 to 0.82 +/- 0.11, P < 0.05), and increased urinary cAMP (0.18 +/- 0.02 to 0.53 +/- 0.05 nmol/L of glomerular filtrate, P = 0.0001). hPTH(1-34) infusion suppressed endogenous intact PTH (18 +/- 3 to 14 +/- 2 ng/L, P < 0.005) and increased PRA from 0.14 +/- 0.02 to 0.32 +/- 0.05 ng/(L.s) (P < 0.05) without a change in serum ionized calcium which suggests direct effects of hPTH(1-34) on the parathyroid glands and the juxtaglomerular apparatus. The effects of AII and hPTH(1-34) were antagonistic with little change in serum ionized calcium, intact PTH, or PRA when both were infused together. These interrelationships between the major hormonal systems controlling sodium and calcium homeostasis suggest a mechanism underlying the close association of calcium and sodium in the regulation of blood pressure.