title: Apelin elevates blood pressure in ICR mice with L‑NAME‑induced endothelial dysfunction.
abstract: Apelin is the endogenous ligand of APJ, which belongs to the family of G protein‑coupled receptors. Apelin and APJ are highly expressed in various cardiovascular tissues, including the heart, kidney and vascular endothelial and smooth muscle cells. Although apelin exerts hypotensive effects via activation of endothelial nitric oxide synthase (eNOS), the ability of apelin to regulate blood pressure under pathological conditions is poorly understood. In the current study, NG‑nitro‑L‑arginine methyl ester (L‑NAME), a potent NOS inhibitor, was administered chronically, to induce peripheral vascular damage in mice. L‑NAME‑treated mice exhibited hypertension, increased vascular cell adhesion molecule‑1 and plasminogen activator inhibitor‑1 mRNA levels in the aorta and impaired vasodilatation associated with decreased aortic eNOS expression, consistent with endothelial damage. Three days following withdrawal of L‑NAME treatment, the blood pressure response to apelin stimulation was assessed. Although apelin reduced blood pressure in non‑treated mice, it was found to transiently elevate blood pressure in L‑NAME‑treated mice. These results indicate that apelin functions as a vasopressor peptide under pathological conditions, including vascular endothelial dysfunction in mice.
authors.affiliation: Life Science Center, Tsukuba Advanced Research Alliance, Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305‑8577, Japan.
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Nagano
authors.forename: Junji
authors.initials: J
authors.lastname: Ishida
authors.forename: Madoka
authors.initials: M
authors.lastname: Unno
authors.forename: Tanomu
authors.initials: T
authors.lastname: Matsukura
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D019331:NG-Nitroarginine Methyl Ester; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D013599:Systole / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D014662:Vasoconstrictor Agents; C495199:apelin-13 peptide; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester