title: Atypical antipsychotics such as risperidone, but not paliperidone, worsen vascular endothelial function via upregulation of adhesion molecules VCAM-1, ICAM-1, and E-selectin in diabetic rats.
abstract: Schizophrenia doubles the odds of diabetes, and atypical antipsychotics (AAPs) also increase risk of diabetes. Indeed, little is known about the effects of AAPs on vascular dysfunctions associated with diabetes. This study aimed to determine the effects of risperidone (RISP) and paliperidone (PALI) on the vascular function of diabetic rats. Diabetes was induced by feeding with a high-fat diet followed by the administration of streptozotocin (35 mg·(kg body mass)(-1), by intraperitoneal injection). Rats received RISP or PALI (1.25 mg·kg(-1)·d(-1), per os) for 3 weeks. Endothelium-dependent relaxation, systolic blood pressure, lipid profile, insulin resistance, and adhesion molecules, vascular cell-adhesion-molecule-1 (VCAM-1), intracellular-adhesion-molecule-1 (ICAM-1), and E-selectin were investigated. RISP significantly worsened the impaired endothelium-dependent relaxation of diabetic aortic rings with upregulation of the adhesion molecules VCAM-1, ICAM-1, and E-selectin, and proinflammatory cytokines MPC-1 and TNF-α. RISP augmented the metabolic dysfunctions and reduced insulin sensitivity in the insulin tolerance test as well as HOMA-IR. PALI produced insignificant effects on vascular and metabolic aberrations. Our results suggest that RISP, but not PALI, aggravates the metabolic abnormalities and vascular dysfunction associated with diabetes, which may be mediated by upregulation of VCAM-1, ICAM-1, and E-selectin. Nevertheless, future investigation for the possible mechanisms underlying the difference noticed between the 2 AAPs is warranted.
authors.affiliation: a Department of Pharmacology, Faculty of Medicine, Ain Shams University, Abbassia, Cairo 11566, Egypt.
authors.forename: Sawsan
authors.initials: S
authors.lastname: Aboul-Fotouh
authors.forename: Nesreen
authors.initials: N
authors.lastname: Elgayar
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D018932:Chemokine CCL2 / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D007555:Isoxazoles / Q000494:pharmacology; D008055:Lipids / Q000235:genetics; D008297:Male; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; C491766:Ccl2 protein, rat; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D016207:Cytokines; D019040:E-Selectin; D007555:Isoxazoles; D008055:Lipids; D011743:Pyrimidines; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D005947:Glucose; D018967:Risperidone; D000068882:Paliperidone Palmitate