Recombinant human growth hormone administered for three months to patients with idiopathic dilated cardiomyopathy increased myocardial mass and reduced the size of the left ventricular chamber, resulting in improvement in hemodynamics, myocardial energy metabolism, and clinical status.
Background — Although thyroid hormone (TH) exerts relevant effects on the cardiovascular system, it is unknown whether TH also regulates vascular reactivity in humans. Methods and Results — We studied 8 patients with hyperthyroidism, basally (H) and 6 months after euthyroidism was restored by methimazole (EU). Thirteen healthy subjects served as control subjects (C). We measured forearm blood flow (FBF) by strain-gauge plethysmography during intrabrachial graded infusion of acetylcholine, sodium nitroprusside (SNP), norepinephrine, and L-NMMA (inhibitor of NO synthesis). Basal FBF (in mL · dL −1 · min −1 ) was markedly higher in H than in C (5.8±1.2 and 1.9±0.1, respectively; P <0.001) and was close to normal in EU (2.6±0.3, P <0.01 versus H). During acetylcholine infusion, FBF increased much more in H (+33±5) than in C (+14±3, P <0.01 versus H) and in EU (+20±5, P =0.01 versus H and P =NS versus C). In contrast, the response to SNP infusion was comparable in the patients and control subjects. During norepinephrine infusion, the fall in FBF was much more pronounced in H (−6±1) than in C (−0.7±0.3, P <0.005 versus H) and in EU (−1.5±0.3, P <0.01 versus H). Finally, inhibition of NO synthesis by L-NMMA decreased FBF by 2.8±0.6, 0.61±0.7, and 1.4±0.3 in H, C, and EU, respectively (H versus C and EU, P <0.05). Conclusions — In hyperthyroidism, (1) the marked basal vasodilation is largely accounted for by excessive endothelial NO production, (2) vascular reactivity is exaggerated because of enhanced sensitivity of the endothelial component, (3) the vasoconstrictory response to norepinephrine is potentiated, and (4) this abnormal vascular profile is corrected when euthyroidism is restored by medical therapy. The data demonstrate that vascular endothelium is a specific target of TH.
In rats with streptozotocin-induced diabetes, balloon injury was not associated with an increase in neointimal formation. Exogenous insulin administration in diabetic rats and islet transplantation in nondiabetic rats increased both blood insulin levels and neointimal hyperplasia after balloon injury. Hyperinsulinemia through activation of the ras/MAPK pathway, rather than hyperglycemia per se, seems to be of crucial importance in determining the exaggerated neointimal hyperplasia after balloon angioplasty in diabetic animals.
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 22Ϯ3 years, body mass index [BMI] 25Ϯ1 kg/m 2 ) and 10 healthy subjects (age 24Ϯ0.4 years, BMI 22Ϯ1 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 (PϽ0.05). Likewise, forearm release of nitrite and cGMP during acetylcholine stimulation was reduced in GH-deficient nontreated patients (PϽ0.05 and PϽ0.002 versus controls). The response to the endothelium-independent vasodilator sodium nitroprusside was also markedly blunted in GH-deficient patients compared with control subjects (PϽ0.005). To confirm that abnormal vascular reactivity was due to GHD, we also studied 8 patients with childhood-onset GHD (age 31Ϯ2 years, BMI 24Ϯ1 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 (17.2Ϯ2.6 mL ⅐ dL Ϫ1 ⅐ min Ϫ1 , PϽ0.01) but not in GH-treated patients (24.8Ϯ3.3 mL ⅐ dL Ϫ1 ⅐ min Ϫ1 ) compared with normal subjects (29.5Ϯ3.2 mL ⅐ dL Ϫ1 ⅐ min Ϫ1 ). Conclusions-The
Very little is known about the atherosclerotic risk in patients with childhood-onset growth hormone deficiency (GHD). Such data may be relevant to reconstructing the natural course of the cardiovascular abnormalities associated with GHD. To this end, the intima-media thickness (IMT) of the carotid arteries and the vascular risk factors were evaluated in 14 childhood-onset GHD patients (age 25 +/- 1 yr, BMI 22 +/- 0.6 Kg/m2) and in 14 age-, sex-, and BMI-matched control subjects. IMT was greater in GHD patients (0.83 +/- 0.06 and 0.81 +/- 0.06 mmol/L for the right and left carotid artery) than in controls (0.64 +/- 0.03 and 0.64 +/- 0.04 mmol/L, P < 0.01 and P < 0.02, respectively). Serum total and lipoprotein cholesterol, and serum total triglycerides did not differ between the two groups. However, a significant increase in low density lipid triglycerides was present in GHD patients (0.27 +/- 0.02 mmol/L) compared with controls (0.19 +/- 0.01; P = 0.007). No difference was found in plasma fibrinogen and serum Lp(a) levels. Plasma glucose and insulin concentrations were similar in GHD and control subjects both in the fasted state and after an oral glucose load. In conclusion, young patients with childhood-onset GHD show an increased IMT in the absence of clear-cut abnormalities of the classic vascular risk factors. This suggests a role for GH deficiency per se in increasing the atherosclerotic risk.
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