Abnormal vascular reactivity in growth hormone deficiency

Background-The reason why patients with growth hormone (GH) deficiency (GHD) are at increased risk for premature cardiovascular death is still unclear. Although a variety of vascular risk factors have been identified in GHD, little is known regarding vascular reactivity and its contribution to premature arteriosclerosis. Methods and Results-We assessed vascular function in 7 childhood-onset, GH-deficient nontreated patients (age 22+/-3 years, body mass index [BMI] 25+/-1 kg/m(2)) and 10 healthy subjects (age 24+/-0.4 years, BMI 22+/-1 kg/m(2)) by using strain gauge plethysmography to measure forearm blood flow in response to vasodilatory agents. The increase in forearm blood flow to intrabrachial infusion of the endothelium-dependent vasodilator acetylcholine was significantly lower in GH-deficient nontreated patients than in control subjects (P<0.05). Likewise, forearm release of nitrite and cGMP during acetylcholine stimulation was reduced in GH-deficient nontreated patients (P<0.05 and P<0.002 versus controls). The response to the endothelium-independent vasodilator sodium nitroprusside was also markedly blunted in GH-deficient patients compared with control subjects (P<0.005). To confirm that abnormal vascular reactivity was due to GHD, we also studied 8 patients with childhood-onset GHD (age 31+/-2 years, BMI 24+/-1 kg/m(2)) who were receiving stable GH replacement therapy. In these patients, the response to both endothelium-dependent and -independent vasodilators, as well as forearm nitrite and cGMP, release was not different from that observed in normal subjects. Peak hyperemic response to 5-minute forearm ischemia was significantly reduced in GH-deficient nontreated patients (17.2+/-2.6 mL . dL(-1) . min(-1), P<0.01) but not in GH-treated patients (24.8+/-3.3 mL . dL(-1) . min(-1)) compared with normal subjects (29.5+/-3.2 mL . dL(-1) . min(-1)). Conclusions-The data support the concept that GH plays an important role in the maintenance of a normal vascular function in humans.