Is the somatotropic axis related to sympathetic nerve activity in healthy ageing men?

OBJECTIVE: The mechanisms underlying the age-related increase in blood pressure and sympathetic nerve activity remain largely unknown. The decline in growth hormone (GH) secretion and insulin-like growth factor-I (IGF-I) with age has been related to several cardiovascular risk factors. Low serum IGF-I levels in severe adult GH deficiency is associated with markedly increased sympathetic nerve activity. This study evaluates whether a relationship between serum IGF-I and sympathetic nerve traffic exists in healthy aging men. DESIGN AND METHODS: Sympathetic nerve activity to the muscle vascular bed (MSA) was recorded in 56 healthy normotensive males, and related to age (range 21-71 years), body mass index (BMI, range 18.4-32.2), serum IGF-I and plasma nitrate levels. Blood pressure, BMI and MSA increased with age, whereas IGF-I and plasma nitrate decreased. In a forward stepwise multiple regression analysis, age explained 40% of the variability in MSA and excluded other variables. Omitting age, IGF-I became the strongest independent predictor, explaining 23% of the variability in MSA. MSA was an independent predictor of diastolic blood pressure, but its influence (10%) was less than that of BMI (28%). BMI was not related to MSA or IGF-I. CONCLUSIONS: Decreased serum IGF-I levels are coupled to increased MSA during ageing, an effect independent from the impact of increased body weight. Although MSA is a weak predictor of rising blood pressure with age, it constitutes one possible pathway for the somatotropic axis to affect cardiovascular function in ageing

Diabetic ketosis activates lymphomonocyte-inducible nitric oxide synthase.

Inappropriate production of nitric oxide (NO) may be responsible for the haemodynamic disturbances of diabetic ketoacidosis. We investigated whether this metabolic condition is associated with increased plasma nitrate (the stable oxidation product of NO) levels and NO synthase gene expression in lymphomonocytes. RESEARCH DESIGN AND METHODS: Plasma nitrate concentrations, lymphomonocyte-inducible nitric oxide synthase (iNOS) gene expression, tumour necrosis factor-alpha (TNF-alpha) and soluble thrombomodulin were measured in 11 Type 1 diabetic patients at baseline, during mild ketosis and after euglycaemia was re-established. RESULTS: During diabetic ketosis plasma nitrate concentrations were higher (18 (16-21) vs. 9 (7-11) micro mol/l; (95% lower-upper confidence interval) P < 0.05) than at baseline. At baseline lymphomonocyte iNOS mRNA expression and iNOS protein levels were undetectable, but in ketosis both were increased (both at P < 0.0001). After recovery from ketosis, NO3 concentration, iNOS mRNA, and iNOS expression (270 +/- 36%, mean +/- sd) decreased but not significantly. No significant changes were observed in either TNF-alpha or soluble thrombomodulin levels between the three conditions. CONCLUSIONS: Diabetic ketosis is associated with increased nitrate levels and the activation of iNOS expression in circulating lymphomonocytes, but it does not affect either the proinflammatory cytokine TNF-alpha or a marker of endothelial dysfunction such as thrombomodulin. Our data support the hypothesis that, during diabetic ketosis, alterations in NO homeostasis are present in circulating lymphomonocytes