Cyclic GMP-phosphodiesterase inhibition does not alter cerebral oxygen consumption.
The effect of zaprinast, a cyclic guanosine monophosphate inhibitor, on the level of cyclic GMP and cerebral O2 consumption was determined. Anesthetized male Long-Evans rats were divided into a control group (n = 15) and a zaprinast treated group (n = 15). Vehicle was applied topically to the left cortex and 3*10-3 M zaprinast was applied to the right cortex. A saline treated control group was also studied. Regional cerebral blood flow was determined by [14C]-iodoantipyrine and regional 0(2) extraction was determined by microspectrophotometry. The level of cyclic GMP was measured by radioimmunoassay. There were no hemodynamic or blood gas differences between groups. The level of cyclic GMP was not significantly different between the right and left cerebral cortex of the control group (17.0 + or - 4.3 and 17.7 + or - 4.6 pmol/g). In the zaprinast treated group, there was a significant (46%) increase in the level of cyclic GMP in the zaprinast treated cortex (20.5 + or - 8.1) in comparison to the vehicle treated cortex (14.0 + or - 5.7). Zaprinast did not significantly alter cerebral blood flow. There were no significant differences in regional 0(2) extraction. The 0(2) consumption of the zaprinast treated cortex (8.0 + or - 3.3 ml O(2)*min(-1)*100 g(-1)) was not different from that of the vehicle ) treated cortex (7.0 + or - 2.9) or those of the control group. Thus, our data indicated that the increased level of cyclic GMP had no significant effect on cerebral oxygen consumption.
Wei
H M
HM
Department of Anesthesia, UMDNJ--Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA.
Shah
A J
AJ
Tse
J
J
Chi
O Z
OZ
Weiss
H R
HR
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011688:Purinones / Q000494:pharmacology*; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects*
D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D010100:Oxygen