title: L-arginine in combination with sildenafil potentiates the attenuation of hypoxic pulmonary hypertension in rats.
abstract: Chronic hypoxia induces an increased production of nitric oxide (NO) in pulmonary prealveolar arterioles. Bioavailability of the NO in the pulmonary vessels correlates with concentration of L-arginine as well as activity of phosphodiesterase-5 enzyme (PDE-5). We tested a hypothesis whether a combination of L-arginine and PDE-5 inhibitor sildenafil has an additive effect in reduction of the hypoxic pulmonary hypertension (HPH) in rats. Animals were exposed to chronic normobaric hypoxia for 3 weeks. In the AH group, rats were administered L-arginine during chronic hypoxic exposure. In the SH group, rats were administered sildenafil during chronic hypoxic exposure. In the SAH group, rats were treated by the combination of L-arginine as well as sildenafil during exposure to chronic hypoxia. Mean PAP, structural remodeling of peripheral pulmonary arterioles (%DL) and RV/LV+S ratio was significantly decreased in the SAH group compared to hypoxic controls even decreased compared to the AH and the SH groups in first two measured parameters. Plasmatic concentration of cGMP and NOx were significantly lower in the SAH group compared to hypoxic controls. We demonstrate that NO synthase substrate L-arginine and phosphodiesterase-5 inhibitor sildenafil administered in combination are more potent in attenuation of the HPH compared to a treatment by substances given alone.
authors.affiliation: Department of Physiology, Second Medical School, Charles University, Prague, Czech Republic. milan.chovanec@lfmotol.cuni.cz.
authors.forename: H
authors.initials: H
authors.lastname: Al-Hiti
authors.forename: M
authors.initials: M
authors.lastname: Chovanec
authors.forename: V
authors.initials: V
authors.lastname: Melenovský
authors.forename: O
authors.initials: O
authors.lastname: Vajnerová
authors.forename: A
authors.initials: A
authors.lastname: Baňasová
authors.forename: J
authors.initials: J
authors.lastname: Kautzner
authors.forename: J
authors.initials: J
authors.lastname: Herget
mesh_terms: D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D010879:Piperazines / Q000008:administration & dosage*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011687:Purines / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D001120:Arginine; D000068677:Sildenafil Citrate