Dopamine agonists play an important role in the regulation of the central nervous-cardiovascular, renal, and hormonal systems through stimulation of dopaminergic (DA1 and DA2) and alpha- and beta-adrenergic receptors. Several studies have shown that in fat and diabetic mice. The aim of the present study was to evaluate the interaction of the dopaminergic and endocrine systems by determining the effect of the dopaminergic antagonist, metoclopramide, and dopamine on insulin secretion and cardiovascular response by blockade and activation of dopamine receptors in healthy and type 2 diabetic subjects. Healthy subjects (n =15) and subjects with type 2 diabetes (n = 15) of both genders, aged 18 to 60 years, were recruited into this study. A comparative experimental design of 90 minutes was performed in which placebo (0.9% saline) was infused intravenously for the first 30 minutes followed by metoclopramide (7.5 microg/kg/min), a dopamine receptor antagonist for 30 minutes, and then metoclopramide (7.5 microg/kg/min) plus dopamine (0.5-3 microg/kg/min) for 30 minutes. The following clinical and biochemical parameters were measured at the beginning and then every 30 minutes of the experimental period (30', 60' and 90'): systolic-diastolic and mean arterial blood pressure, heart rate, serum glucose, insulin, triacylglycerides, and total cholesterol. Baseline glycosylated hemoglobin was measured and homeostasis model assessment for insulin resistance was calculated from insulin and glucose levels. Twelve-lead electrocardiograms were also obtained at these points. Dopamine infusion induced an increase in serum insulin, systolic blood pressure, and heart rate in healthy subjects but not in subjects with type 2 diabetes. Infusion of metoclopramide induced a hypotensive effect in healthy subjects, which was blunted by inclusion of dopamine in the infusion mixture. In subjects with diabetes, metoclopramide had no effect on blood pressure, but addition of dopamine raised systolic blood pressure. Neither metoclopramide nor dopamine altered significantly the lipid profile in healthy or diabetic subjects. Dopaminergic drugs increase serum insulin probably by interacting with dopaminergic receptors, but stimulation of beta-adrenergic receptors cannot be ruled out. Stimulation of cardiovascular dopamine receptors also caused modifications of hemodynamic parameters in healthy subjects, but apparently these receptors are attenuated in patients with type 2 diabetes probably as a result of endothelial dysfunction and alterations in the sympathetic nervous system sensitivity.

Leptin is a 167 aminoacid peptidic hormone secreted by adipose tissue. It works mainly in the hypothalamus at thirst signal, but given its closed connections with inflammatory and endothelial systems, also has been postulated that it may exert a regulatory control over blood pressure (BP), interacting with nitric oxide (NO) and C reactive protein (CRP). The cold pressor test (CPT) is a simple test that indirectly determines endothelial dysfunction. In this work, biochemical indicators (CRP, leptin, and NO) and hemodynamic indicators (systolic and diastolic BP) were performed and evaluated in hypertensive, type 2 diabetic, and control subjects during a single CPT for assessment of endothelial dysfunction. A total of 43 subjects, males and females aged 25 to 60 years and divided in three groups, 15 healthy volunteers, 13 hypertensive patients, and 15 patients with type 2 diabetes, were included in the study. A complete clinical history was obtained from each subject, and a complete physical examination, including an electrocardiogram was carried out. During the assay of 30 minutes, 0.9% saline was infused intravenously. CPT was performed to assess the cardiovascular reactivity at minute 15. The cardiovascular variables (systolic and diastolic BP) were measured in minute 0, 16, and 30. In addition, serum variables were obtained at the beginning and at the end of the experiment, and statistical analysis was performed. CPT caused in all subjects a significant increase of BP and pulse. There were no significant differences to CPR and leptin in any group, although we observed significant differences for NO (P < 0.05). Sensitivity and specificity for all biochemical variables resulted in nonsignificant statistical or clinical importance as markers of endothelial dysfunction; however, a positive association was found when leptin and NO were evaluated together (sensitivity: 0.2; specificity. 0.8). CRP, leptin, and NO did not shown any direct and significant association with the hemodynamic variables in this study, although a relationship was noted between NO according to group and biochemical variables when studied altogether.