The renin-angiotensin system is activated by short-term, but repressed by long-term growth hormone excess

Abstract Background The renin-angiotensin system (RAS) constitutes an important cornerstone in blood pressure (BP) regulation. Previous evidence on the relationship between growth hormone (GH), insulin-like growth factor I (IGF-I), and the RAS is conflicting, depending on study conditions and exposure duration. This exploratory study therefore investigated the effects of short- and long-term GH excess on RAS activity. Methods RAS activity was assessed in 10 healthy, male volunteers (26±5years, BMI 23±3.4kg/m2) before and after one week of daily, subcutaneous GH treatment (2mg) serving as model of short-term GH excess. Regarding long-term GH excess, RAS activity in 19 patients with active acromegaly (54[48-59]years, 52.6% females, IGF-I/ULN 2.8[2.3-3.3]) was compared to a cohort of 25 controls (39[32-47]years, 76% females). In 12 patients, measurements were re-conducted after successful treatment of acromegaly. Results One week of GH treatment increased IGF-I concentrations to 1.6±0.5 ULN and overall RAS activity, including angiotensin II levels (117.5 ±50.3pMol/L vs. 205.9 ±135.7pMol/L, p=0.03) and the surrogate of renin activity (PRA-S: 149.8 ±63.3pMol/L vs. 269.1 ±177.4pMol/L, p=0.03) alongside increased concentrations of insulin and C-peptide in healthy males. In contrast, patients with acromegaly showed lower concentrations of angiotensin II (47.2[33-145]pMol/L vs. 155.3[64-326]pMol/L, p=0.017), aldosterone (118[71-193]pMol/L vs. 227.8[165-305]pMol/L, p=0.009), and PRA-S(84.2[51-200]pMol/L vs. 230[85-403]pMol/L, p=0.032) despite higher mean arterial BP(105[99-115]mmHg vs. 91[85-97]mmHg, p< 0.001) compared to controls. Conclusion Short-term GH excess stimulates RAS activity which may be related to the increase in insulin and C-peptide. In contrast, RAS activity is down-regulated in long-term GH excess despite high BP.