neuropeptide-y and Carotid-Stenosis

Atherosclerotic-occlusive changes could be observed in orofacial branches of the external carotid artery. Atherosclerosis-induced ischemia caused alteration in production and release of endothelial factors. The aim of this study was to investigate the influence of carotid artery occlusion (10, 30 and 60 min) on vascular effects of norepinephrine (NOR) and neuropeptide Y (NPY) in the isolated glandular branch of the rabbit facial artery, the main feeding artery for the submandibular gland.. Changes in isometric tension were recorded in organ bath studies with arterial rings, before and after carotid artery occlusion.. Concentration-dependent vasocontractile effect of NOR was significantly augmented after 30 and 60 min of carotid occlusion, but only in the rings with intact endothelium. Given alone, NPY showed no effect in isolated glandular branch of the rabbit facial artery, but enhanced NOR vasoconstriction in all the investigated rings. NOR vasocontractile effect enhancement in the presence of NPY was attenuated after 30 and 60 min of carotid occlusion. Also, enhancement of NOR vasoconstriction by NPY was significantly higher in endothelium-intact rings compared to endothelium-denuded rings obtained after 30 and 60 min of carotid occlusion.. The present investigation provides results of increased vasocontractile effect of NOR and decreased enhancing effect of NPY on NOR vasoconstriction in the rabbit facial artery after carotid occlusion that is related to altered endothelium function.

Topics: Animals; Arteries; Carotid Stenosis; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular; Face; Neuropeptide Y; Norepinephrine; Rabbits; Submandibular Gland; Vasoconstriction; Vasoconstrictor Agents; Vasodilation

We reported previously that neuropeptide Y (NPY) induces an atherosclerotic-like lesion that is significantly reduced by NPY-Y1 and NPY-Y5 receptor (R) inhibitors. Because antagonists also inhibit neointima induced by angioplasty alone, we now test whether stress-induced endogenous NPY release mimic these changes.. Rats were nonstressed or stressed (4 degrees C water; 2 hours per day for 14 days) starting immediately before and continuing after carotid artery angioplasty. Stress acutely and chronically increased blood pressure and doubled plasma NPY levels. After 14 days, angioplasty-induced neointima was markedly greater in stressed (than nonstressed) rats, in which most of the vessels became occluded with an atherosclerotic-like lesion containing macrophages, lipids, thrombus, and microvessels that was similar but more inflammatory than the injury in the NPY-treated vessels. Fourteen days after angioplasty combined with stress or NPY, Y1R and Y5R (mRNA and protein) became upregulated in areas of neointima, microvessels, and macrophages in injured carotid arteries. Stress- and NPY-induced changes were completely prevented by a selective Y1R antagonist (0.02 micromol/kg per minute for 14 days), whereas neointima induced by angioplasty alone was reduced by 60%.. Because of sympathetic NPY release, stress may be a less-than-appreciated risk factor for restenosis/atherosclerosis, and Y1R antagonists a potential therapy for these conditions.

Topics: Angioplasty, Balloon; Animals; Blood Pressure; Carotid Artery Diseases; Carotid Artery Injuries; Carotid Stenosis; Chronic Disease; Cold Temperature; Male; Neuropeptide Y; Rats; Rats, Wistar; Receptors, Neuropeptide Y; Recurrence; Risk Factors; RNA, Messenger; Stress, Physiological; Sympathetic Nervous System; Tunica Intima; Tunica Media

Attempts to restore blood flow through atherosclerotic vessels by angioplasty often result in restenosis. Because the role of nerves in this process is unclear, we investigated whether neuropeptide Y (NPY), a sympathetic cotransmitter with vascular mitogenic activities, contributes to postangioplasty restenosis.. Carotid artery balloon angioplasty upregulated vascular expression of NPY and its processing enzyme (DPPIV/cd26) and receptors (Y1, Y2, Y5 mRNA and protein) within 6 to 24 hours and stimulated neointima formation and accumulation of NPY in platelets after 14 days. NPY pellets (1 to 10 microg/pellet for 14 days) inserted next to the injured artery elevated platelet and vascular NPY immunoreactivity to stress-like levels and dose-dependently augmented angioplasty-induced neointima. Strikingly, 10 microg NPY for 14 days led to vessel occlusion with an atherosclerotic-like lesion, with thrombus and neointima containing neovessels, macrophages, matrix, and lipids. Y1 or Y5 receptor antagonist completely prevented the effect of NPY and reduced angioplasty-induced neointima by 50%.. Angioplasty upregulates platelet and vascular NPY systems, which then contribute to neointima formation via Y1 and Y5 receptor activation. Increasing NPY to high stress levels triggers formation of a thrombotic atherosclerotic-like lesion and vessel occlusion. Thus, NPY may be a risk factor for accelerated atherosclerosis, and NPY receptor antagonists may be a possible new treatment for restenosis.

Topics: Analysis of Variance; Angioplasty, Balloon; Animals; Arteriosclerosis; Blood Platelets; Carotid Artery, Common; Carotid Stenosis; Endothelium, Vascular; Male; Neuropeptide Y; Rats; Rats, Wistar; Receptors, Neuropeptide Y; Recurrence; Tunica Intima; Up-Regulation

We have recently demonstrated that subjects having Pro7 in the signal peptide ofneuropeptide Y (NPY) have higher serum cholesterol and apolipoprotein B levels than individuals with wild-type (Leu7Leu7) signal peptide sequence. We investigated the association of Leu7Pro polymorphism with common carotid intima media thickness (IMT) assessed by ultrasonograph in patients with type 2 diabetes (n = 81; 41 men and 40 women; mean age, 67.1 yr) and nondiabetic subjects (n = 105; 48 men and 57 women; mean age, 65.5 yr) and genotyped for the Leu7Pro polymorphism in prepro-NPY. The frequency of Pro7 in prepro-NPY was 9.9% (8 of 81) in diabetic patients and 14.3% (15 of 105) in control subjects (P = 0.360). The mean common carotid IMT was 1.04 +/- 0.02 mm in nondiabetic subjects without the Leu7Pro polymorphism and 1.14 +/- 0.04 mm in nondiabetic subjects with in (P = 0.156) and 1:18 +/- 0.03 and 1.58 +/- 0.21mm in diabetic patients without and with the Leu7Pro polymorphism (P = 0.004), respectively. In the analysis of covariance of the entire group, the mean common carotid IMT was independently associated with the Leu7Pro polymorphism (F = 5.165; P = 0.024) after adjustment for known risk factors. Thus, the presence of the Pro7 substitution in the prepro-NPY associates with increased carotid atherosclerosis.

Topics: Aged; Amino Acid Substitution; Arteriosclerosis; Autonomic Nervous System; Blood Pressure; Carotid Stenosis; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Genotype; Heart Rate; Humans; Leucine; Male; Neuropeptide Y; Polymorphism, Genetic; Proline; Risk Factors

Modifications in the tissue concentration of vasoactive peptides (Endothelin, Calcitonin Gene Related Peptide, Atrial Natriuretic Peptide) and excitatory amino acids (glutamate, aspartate) were found in the nervous tissue of Mongolian gerbils after transient cerebral ischemia which was induced by unilateral occlusion of the common carotid artery for 30 min 4 h. In fact, immunostaining for these peptides was more intense in the ischemic tissue: the greatest increases of tissue immunoreactivity were observed for Endothelin; smaller differences were found for Calcitonin Gene Related Peptide and Atrial Natriuretic Peptide. Immunostaining for Neuropeptide Y, another vasoactive neuropeptide, was virtually unchanged. Infarct areas, when present, contained numerous Endothelin-immunoreactive cell bodies. On the contrary, the same areas were completely void of glutamate- or aspartate-immunostained neurons, normally present in the correspondent regions of the control tissue. The present results suggest that severe cerebral ischemia is paralleled by an unbalance of local vasoactive factors. The predominance of vasoconstrictor action of Endothelin might play a major role in the irreversible damage, together with the excitotoxic effect of the extracellular accumulation of excitatory amino acids, probably due to a leakage from neuronal cell somata, as suggested by the disappearance of glutamate- or aspartate-immunostained neurons.

Topics: Animals; Atrial Natriuretic Factor; Brain Damage, Chronic; Calcitonin Gene-Related Peptide; Carotid Stenosis; Endothelins; Excitatory Amino Acids; Gerbillinae; Ischemic Attack, Transient; Neurons; Neuropeptide Y; Vasoconstriction