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

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.

RAS activity was assessed in 10 healthy, male volunteers (26 ± 5years, BMI 23 ± 3.4 kg/m2) before and after 1 week of daily, subcutaneous GH treatment (2 mg) 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.

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 ± 50.3 pMol/L vs. 205.9 ± 135.7 pMol/L, P = .03) and the surrogate of renin activity (PRA-S: 149.8 ± 63.3 pMol/L vs. 269.1 ± 177.4 pMol/L, P = .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 = .017), aldosterone (118 [71-193] pMol/L vs. 227.8 [165-305] pMol/L, P = .009), and PRA-S(84.2 [51-200] pMol/L vs. 230 [85-403] pMol/L, P = .032) despite higher mean arterial BP(105 [99-115] mmHg vs. 91 [85-97] mmHg, P < .001) compared to controls.

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.