title: Relaxation and cyclic GMP levels in response to sildenafil in human pulmonary arteries from donors.
abstract: We measured cyclic GMP formation and relaxation response to sildenafil given either alone or in combination with sodium nitroprusside (SNP) in pulmonary arteries obtained from 13 multi-organ donors. Sildenafil (10(-9)-10(-4) M) caused concentration-dependent relaxations and amplified the relaxation induced by SNP. Relaxation was unaffected by endothelium removal or by pre-treatment with the inhibitor of nitric oxide synthase L-NMMA (10(-4) M). SNP (10(-7) M) caused elevation of cyclic GMP levels that was potentiated by sildenafil (10(-6) M). Thus, the enhancement of SNP-induced relaxation by sildenafil is mainly due to an increase in cyclic GMP accumulation.
authors.affiliation: Departamento de Fisiología, Universidad de Valencia, Valencia, Spain.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Mauricio
authors.forename: Gloria
authors.initials: G
authors.lastname: Segarra
authors.forename: Pascual
authors.initials: P
authors.lastname: Medina
authors.forename: Martin
authors.initials: M
authors.lastname: Aldasoro
authors.forename: Juan B
authors.initials: JB
authors.lastname: Martínez-León
authors.forename: José M
authors.initials: JM
authors.lastname: Vila
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000328:Adult; D006152:Cyclic GMP / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009599:Nitroprusside; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP