The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism.
Apelin is an endogenous ligand of the human orphan receptor APJ. We detected apelin-like immunoreactivity in the adipocytes, gastric mucosa, and Kupffer cells in the liver. We also detected apelin-like immunoreactivity localized within the endothelia of small arteries in various organs. Further, it was found that mean arterial pressure after the administration of apelin-12, apelin-13, and apelin-36 at a dose of 10 nmol/kg in anaesthetized rats was reduced by 26+/-5, 11+/-4, and 5+/-4 mm Hg, respectively. In the presence of a nitric oxide (NO) synthase inhibitor, the effect of apelin-12 on blood pressure was abolished. Furthermore, the administration of apelin-12 (10 nmol/kg) in rats produced a transitory elevation of the plasma nitrite/nitrate concentration from a basal level of 21.4+/-1.6 to 27.0+/-1.5 microM. Thus, apelin may lower blood pressure via a nitric oxide-dependent mechanism.
Tatemoto
K
K
Department of Molecular Physiology, Institute for Molecular and Cellular Regulation, Gunma University, 371-8512, Maebashi, Japan. tatekazu@akagi.sb.gumma-u.ac.jp
Takayama
K
K
Zou
M X
MX
Kumaki
I
I
Zhang
W
W
Kumano
K
K
Fujimiya
M
M
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000138:chemical synthesis; D000073861:Apelin; D000075244:Apelin Receptors; D001794:Blood Pressure / Q000187:drug effects*; D002352:Carrier Proteins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood; D009928:Organ Specificity; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled
C104575:APLNR protein, human; D000959:Antihypertensive Agents; D000073861:Apelin; D000075244:Apelin Receptors; C498579:Apln protein, rat; C491284:Aplnr protein, rat; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D009566:Nitrates; D009573:Nitrites; D010455:Peptides; D017448:Receptors, Dopamine D2; D043562:Receptors, G-Protein-Coupled; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester