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. Author manuscript; available in PMC: 2015 Jun 1.
Published in final edited form as: Curr Opin Endocrinol Diabetes Obes. 2014 Jun;21(3):193–201. doi: 10.1097/MED.0000000000000062

Figure 1. Interactions between Calcium-Regulatory Hormones and the Renin-Angiotensin-Aldosterone System.

Figure 1

Increasing evidence supports multiple, complex interactions between the calcium-regulatory system and the RAAS, and these interactions are relevant to both cardiovascular and skeletal disease. Shown on the left is a simplified diagram of the key components of the calcium-regulating system, and on the right, from bottom to top, is a simplified schematic of the RAAS. Solid arrows denote established interactions within the calcium- and adrenal-regulatory hormone systems, respectively. Dashed arrows indicate newly appreciated interactions between the two systems. Black arrows indicate a stimulatory relationship, whereas grey lines terminating in a bar indicate an inhibitory relationship. Arrows A and B depict RAAS-mediated stimulation of the calcium-regulatory system. (A) Chronic exposure to aldosterone stimulates PTH, possibly secondary to urinary calcium loss, though the mineralocorticoid receptor is expressed in the parathyroid [14**,15**,16*]. (B) AngII acutely stimulates PTH, and the angiotensin type 1 receptor is expressed in parathyroid tissue [17**]. Arrows C-F show Ca-, PTH-, and Vitamin D-mediated control of the RAAS. (C) Ca acutely inhibits renin release, but chronic elevations in Ca may stimulate renin production [18]. (D) PTH augments the aldosterone response to AngII [19], and PTH receptors are expressed in aldosterone-producing cells [20]. (E) PTH directly stimulates renin in vitro [21], and PTH infusion results in increased AngII levels [22]. (F) The 1,25(OH)2D-Vitamin D Receptor complex inhibits renin expression in vitro [23**], insufficient Vitamin D status has been associated with increased plasma renin activity [24], and Vitamin D supplementation can downregulate the RAAS [25**]. RAAS, renin-angiotensin-aldosterone system; PTH, parathyroid hormone; 1,25(OH)2D, 1,25-dihydroxyvitamin D; Ca, calcium; AGT, angiotensinogen; AngI, angiotensin I; ACE, angiotensin converting enzyme; AngII, angiotensin II.