title: Beneficial Effects of Apelin on Vascular Function in Patients With Central Obesity.
abstract: Patients with central obesity have impaired insulin-stimulated vasodilation and increased ET-1 (endothelin 1) vasoconstriction, which may contribute to insulin resistance and vascular damage. Apelin enhances insulin sensitivity and glucose disposal but also acts as a nitric oxide (NO)-dependent vasodilator and a counter-regulator of AT1(angiotensin [Ang] II type 1) receptor-induced vasoconstriction. We, therefore, examined the effects of exogenous (Pyr1)apelin on NO-mediated vasodilation and Ang II- or ET-1-dependent vasoconstrictor tone in obese patients. In the absence of hyperinsulinemia, forearm blood flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during saline or apelin administration (bothP>0.05). During intra-arterial infusion of regular insulin, however, apelin enhanced the vasodilation induced by both acetylcholine and nitroprusside (bothP<0.05). Interestingly, the vasodilator effect of concurrent blockade of AT1(telmisartan) and AT2(PD 123,319) receptors was blunted by apelin (3±5% versus 32±9%;P<0.05). Similarly, during apelin administration, blockade of ETAreceptors (BQ-123) resulted in lower vasodilator response than during saline (23±10% versus 65±12%;P<0.05). NO synthase inhibition by L-NMMA (l-N-monometylarginine) during the concurrent blockade of either Ang II or ETAreceptors resulted in similar vasoconstriction in the absence or presence of apelin (P>0.05). In conclusion, in patients with central obesity, apelin has favorable effects not only to improve insulin-stimulated endothelium-dependent and endothelium-independent vasodilator responses but also to blunt Ang II- and ET-1-dependent vasoconstriction by a mechanism not involving NO. Taken together, our results suggest that targeting the apelin system might favorably impact some hemodynamic abnormalities of insulin-resistant states like obesity.
authors.affiliation: From the Departments of Internal Medicine (F.S., C.C.), Surgery (A.V.), Pharmacology (N.M.), and Biochemistry (A.B.), Catholic University, Rome, Italy; and Department of Internal Medicine, University of Tor Vergata, Rome, Italy (N.D.D., M.T.).
authors.forename: Francesca
authors.initials: F
authors.lastname: Schinzari
authors.affiliation: From the Departments of Internal Medicine (F.S., C.C.), Surgery (A.V.), Pharmacology (N.M.), and Biochemistry (A.B.), Catholic University, Rome, Italy; and Department of Internal Medicine, University of Tor Vergata, Rome, Italy (N.D.D., M.T.).
authors.forename: Augusto
authors.initials: A
authors.lastname: Veneziani
authors.affiliation: From the Departments of Internal Medicine (F.S., C.C.), Surgery (A.V.), Pharmacology (N.M.), and Biochemistry (A.B.), Catholic University, Rome, Italy; and Department of Internal Medicine, University of Tor Vergata, Rome, Italy (N.D.D., M.T.).
authors.forename: Nadia
authors.initials: N
authors.lastname: Mores
authors.affiliation: From the Departments of Internal Medicine (F.S., C.C.), Surgery (A.V.), Pharmacology (N.M.), and Biochemistry (A.B.), Catholic University, Rome, Italy; and Department of Internal Medicine, University of Tor Vergata, Rome, Italy (N.D.D., M.T.).
authors.forename: Angela
authors.initials: A
authors.lastname: Barini
authors.affiliation: From the Departments of Internal Medicine (F.S., C.C.), Surgery (A.V.), Pharmacology (N.M.), and Biochemistry (A.B.), Catholic University, Rome, Italy; and Department of Internal Medicine, University of Tor Vergata, Rome, Italy (N.D.D., M.T.).
authors.forename: Nicola
authors.initials: N
authors.lastname: Di Daniele
authors.affiliation: From the Departments of Internal Medicine (F.S., C.C.), Surgery (A.V.), Pharmacology (N.M.), and Biochemistry (A.B.), Catholic University, Rome, Italy; and Department of Internal Medicine, University of Tor Vergata, Rome, Italy (N.D.D., M.T.). carmine.cardillo@unicatt.it.
authors.forename: Carmine
authors.initials: C
authors.lastname: Cardillo
authors.affiliation: From the Departments of Internal Medicine (F.S., C.C.), Surgery (A.V.), Pharmacology (N.M.), and Biochemistry (A.B.), Catholic University, Rome, Italy; and Department of Internal Medicine, University of Tor Vergata, Rome, Italy (N.D.D., M.T.).
authors.forename: Manfredi
authors.initials: M
authors.lastname: Tesauro
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D017302:Annexins / Q000187:drug effects*; D000073861:Apelin; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology*; D011725:Pyridines / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D000077333:Telmisartan; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: C115436:APLN protein, human; D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D017302:Annexins; D000073861:Apelin; D001562:Benzimidazoles; D001565:Benzoates; D007093:Imidazoles; D036341:Intercellular Signaling Peptides and Proteins; D011725:Pyridines; C052038:vasocortin; C073402:PD 123319; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000109:Acetylcholine; D000077333:Telmisartan
keywords: angiotensin II; endothelin-1; insulin; obesity; vasodilation