Neuropeptide Y induces ischemic angiogenesis and restores function of ischemic skeletal muscles.

Previously we showed that neuropeptide Y (NPY), a sympathetic vasoconstrictor neurotransmitter, stimulates endothelial cell migration, proliferation, and differentiation in vitro. Here, we report on NPY's actions, receptors, and mediators in ischemic angiogenesis. In rats, hindlimb ischemia stimulates sympathetic NPY release (attenuated by lumbar sympathectomy) and upregulates NPY-Y2 (Y2) receptor and a peptidase forming Y2/Y5-selective agonist. Exogenous NPY at physiological concentrations also induces Y5 receptor, stimulates neovascularization, and restores ischemic muscle blood flow and performance. NPY-mediated ischemic angiogenesis is not prevented by a selective Y1 receptor antagonist but is reduced in Y2(-/-) mice. Nonischemic muscle vascularity is also lower in Y2(-/-) mice, whereas it is increased in NPY-overexpressing rats compared with their WT controls. Ex vivo, NPY-induced aortic sprouting is markedly reduced in Y2(-/-) aortas and spontaneous sprouting is severely impaired in NPY(-/-) mice. NPY-mediated aortic sprouting, but not cell migration/proliferation, is blocked by an antifetal liver kinase 1 antibody and abolished in mice null for eNOS. Thus, NPY mediates neurogenic ischemic angiogenesis at physiological concentrations by activating Y2/Y5 receptors and eNOS, in part due to release of VEGF. NPY's effectiveness in revascularization and restoring function of ischemic tissue suggests its therapeutic potential in ischemic conditions.

Plasma neuropeptide Y immunoreactivity influences left ventricular mass in pheochromocytoma.

UNLABELLED: Left ventricular hypertrophy (LVH) in patients with arterial hypertension is closely related to the levels of blood pressure (BP), catecholamines, angiotensin II and other mitogenic peptides. Pheochromocytoma (pheo) is a type of hypertension caused by excessive production of catecholamines. The aim of this study was to determinate if left ventricular hypertrophy in patients with pheochromocytoma is related to catecholamines and neuropeptide Y (NPY). METHODS: 29 patients with pheochromocytoma (22 F, age 40 +/- 13 years), plasma concentration of neuropeptide Y immunoreactivity, noradrenaline (NA), and adrenaline (A) were determined. Twenty-four hour urine collection for determination of noradrenaline and adrenaline were performed. Every patient had echocardiographic examination and 24 h ambulatory blood pressure monitoring. RESULTS: Left ventricular hypertrophy was diagnosed in 14 patients. No differences in systolic and diastolic blood pressure in patients with and without left ventricular hypertrophy were found. Plasma noradrenaline and adrenaline levels did not differ between both groups, while plasma neuropeptide Y immunoreactivity was higher in patients with left ventricular hypertrophy than in patients without left ventricular hypertrophy (18.46 +/- 13.26 vs. 9.3 +/- 5.9 fmol/ml (p = 0.02)). Left ventricular mass index (LVMI) correlated with plasma neuropeptide Y-immunoreactivity (r = 0.42 p = 0.023), however, no relationship between left ventricular mass index and plasma or urine noradrenaline and adrenaline levels were found. CONCLUSION: Our results indicate that mitogenic effect of neuropeptide Y may play a role in pathogenesis of left ventricular hypertrophy in patients with pheochromocytoma.

Do catecholamines influence the level of plasma leptin in patients with phaeochromocytoma?

The relationship between plasma leptin and catecholamine concentrations during chronic and acute catecholamine excess is studied. Patients with phaeochromocytoma, divided according to gender, were examined under basal conditions (n=18) and at selected time-points during surgical removal of the tumour (n=12). Appropriate controls were used (n=23) for the basal study. Plasma leptin was determined by radioimmunoassay (RIA) and plasma noradrenaline (NA) and adrenaline (A) by highperformance liquid chromatography (HPLC). Statistical evaluation employed Student's t-test, Wicoxon test and Spearman's correlation coefficient. Gender-related differences in plasma leptin in normal subjects was confirmed, and these were maintained in the patients. Phaeochromocytoma patients had normal plasma leptin levels in the basal state and decreased levels following the massive catecholamine surge provoked by surgery. Plasma leptin concentration did not correlate with plasma NA or A in either group studied. In the patients with phaeochromocytoma, acute but not chronic catecholamine excess affected plasma leptin, suggesting a role for sympathetic activity in modulating leptin release.

Do catecholamines influence the level of plasma leptin in patients with phaeochromocytoma?

The relationship between plasma leptin and catecholamine concentrations during chronic and acute catecholamine excess is studied. Patients with phaeochromocytoma, divided according to gender, were examined under basal conditions (n = 18) and at selected time-points during surgical removal of the tumour (n = 12). Appropriate controls were used (n = 23) for the basal study. Plasma leptin was determined by radioimmunoassay (RIA) and plasma noradrenaline (NA) and adrenaline (A) by high-performance liquid chromatography (HPLC). Statistical evaluation employed Student's t-test, Wicoxon test and Spearman's correlation coefficient. Gender-related differences in plasma leptin in normal subjects was confirmed, and these were maintained in the patients. Phaeochromocytoma patients had normal plasma leptin levels in the basal state and decreased levels following the massive catecholamine surge provoked by surgery. Plasma leptin concentration did not correlate with plasma NA or A in either group studied. In the patients with phaeochromocytoma, acute but not chronic catecholamine excess affected plasma leptin, suggesting a role for sympathetic activity in modulating leptin release.

The effects of genetic factors on selected indicators of the activity of the sympathoadrenal system and the renin-angiotensin-aldosterone system in twins.

BACKGROUND: There are numerous data indicating a significant role of the sympathoadrenal system and the reninangiotensin- aldosterone system in the regulation of blood pressure and the pathogenesis of essential hypertension. However, the genetic background of essential hypertension remains unclear. AIM: To determine the effects of genetic factors on selected indicators of the activity of the sympathoadrenal system and the renin-angiotensin-aldosterone system in twins. METHODS: We studied 39 monozygotic twin pairs (age 33+/-7 years) and 37 same-gender dizygotic twin pairs (age 36+/-7 years). We measured blood and urine adrenaline (A), noradrenaline (NA), dopamine (DA) and aldosterone (ALD) levels, as well as plasma renin activity (PRA) and serum angiotensin-converting enzyme (ACE) activity. Parameters of the genetic models for age- and gender-adjusted data were estimated by model fitting and path analysis technique using LISREL 8. RESULTS: The effects of genetic factors on the variability of blood and urine catecholamine levels were 69% and 65% for A, 42% and 76% for NA, and 58% and 40% for DA, respectively. We also found shared environmental components for blood NA (28%) and urine DA (17%). Genetic factors accounted for 36% of the variability of PRA and 80% of the variability of ACE. ALD levels were related only to environmental factors (including a shared environmental component, estimated at 25%, for urine ALD). CONCLUSIONS: We found significant effects of genetic factors on the activity of the sympathoadrenal system, as indicated by blood and urine catecholamine levels. We also found the effect of genetic factors on PRA and ACE, but not on aldosterone levels.