Relaxation and cyclic GMP levels in response to sildenafil in human pulmonary arteries from donors.
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.
Mauricio
Maria D
MD
Departamento de Fisiología, Universidad de Valencia, Valencia, Spain.
Segarra
Gloria
G
Medina
Pascual
P
Aldasoro
Martin
M
Martínez-León
Juan B
JB
Vila
José M
JM
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*
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