Zaprinast increases cyclic GMP levels in plasma and in aortic tissue of rats.
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.
Dundore
R L
RL
Department of Vascular and Biochemical Pharmacology, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, PA 19426-0900.
Clas
D M
DM
Wheeler
L T
LT
Habeeb
P G
PG
Bode
D C
DC
Buchholz
R A
RA
Silver
P J
PJ
Pagani
E D
ED
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
D011688:Purinones; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D006152:Cyclic GMP