title: Zaprinast increases cyclic GMP levels in plasma and in aortic tissue of rats.
abstract: The purpose of this study was to determine if significant relationships exist between plasma and aortic cyclic GMP (cGMP) levels and pharmacodynamic effect after the i.v. administration of the cGMP-selective phosphodiesterase inhibitor zaprinast to conscious, spontaneously hypertensive rats. Zaprinast dose-dependently increased plasma and aortic cGMP levels at 10, 18 and 30 mg/kg and decreased mean arterial blood pressure (MAP) at 18 and 30 mg/kg. The concentrations of cGMP in the plasma and in the aorta were significantly correlated (r = 0.765, P < 0.0001). The changes in MAP were significantly correlated to aortic (r = -0.750, P < 0.0001) and plasma (r = -0.762, P < 0.0001) cGMP levels. We conclude that plasma cGMP may be an index of cGMP-selective phosphodiesterase inhibition in vivo.
authors.affiliation: Department of Vascular and Biochemical Pharmacology, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, PA 19426-0900.
authors.forename: R L
authors.initials: RL
authors.lastname: Dundore
authors.forename: D M
authors.initials: DM
authors.lastname: Clas
authors.forename: L T
authors.initials: LT
authors.lastname: Wheeler
authors.forename: P G
authors.initials: PG
authors.lastname: Habeeb
authors.forename: D C
authors.initials: DC
authors.lastname: Bode
authors.forename: R A
authors.initials: RA
authors.lastname: Buchholz
authors.forename: P J
authors.initials: PJ
authors.lastname: Silver
authors.forename: E D
authors.initials: ED
authors.lastname: Pagani
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000704:Analysis of Variance; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D011688:Purinones / Q000008:administration & dosage / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D011688:Purinones; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D006152:Cyclic GMP