title: Involvement of prostacyclin and potassium channels in the diabetes-induced hyporeactivity of the rabbit carotid artery to B-type natriuretic peptide.
abstract: The relation between diabetes and stroke is bidirectional: diabetes is an important risk factor for ischemic stroke, and acute stroke frequently induces hyperglycemia. On the other hand, plasma B-type natriuretic peptide (BNP) levels are raised in diabetes and stroke. The purpose was to study how alloxan-induced diabetes might modify the effects of BNP in rabbit carotid arteries and the mechanisms involved in such actions. To do this, isometric tension in isolated rabbit carotid artery was recorded and prostanoids release and plasma NT-proBNP were measured by enzyme immunoassay. BNP induced a relaxation of phenylephrine-precontracted carotid arteries, and this relaxation was lower in diabetic than in control rabbits. Endothelium removal did not modify the relaxation to BNP in control rabbits but increased this relaxation in diabetic rabbits. In control rabbits, indomethacin inhibited the BNP-induced relaxation in the presence and in the absence of endothelium. In diabetic rabbits, indomethacin did not modify the BNP-induced relaxation in arteries with endothelium and inhibited it in arteries without endothelium. In the presence of BNP the carotid artery released thromboxane A2 and prostacyclin, and the release of endothelial prostacyclin was inhibited in diabetic rabbits. Glibenclamide and 4-aminopyridine inhibited the relaxation to BNP, and these inhibitions were lower in diabetic than in control rabbits. In conclusion, our results provide a new understanding concerning the mechanisms of the diabetes-induced hyporeactivity of the carotid artery to BNP, that at least include the loss of endothelial prostacyclin and a reduced participation of ATP-sensitive K(+) channels (KATP) and voltage-sensitive K(+) channels (KV).
authors: Departamento de Fisiología, Universidad de Valencia, Valencia, Spain.
authors: José M
authors: JM
authors: Centeno
authors: Vannina G
authors: VG
authors: Marrachelli
authors: Luis
authors: L
authors: Miranda
authors: María
authors: M
authors: Castelló-Ruiz
authors: María C
authors: MC
authors: Burguete
authors: Teresa
authors: T
authors: Jover-Mengual
authors: Juan B
authors: JB
authors: Salom
authors: Germán
authors: G
authors: Torregrosa
authors: Francisco J
authors: FJ
authors: Miranda
authors: Enrique
authors: E
authors: Alborch
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000378:metabolism*; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D011817:Rabbits; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D010446:Peptide Fragments; D015221:Potassium Channels; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide; D011464:Epoprostenol; D017461:Receptors, Atrial Natriuretic Factor; D011188:Potassium