A cross-sectional study of platelet cyclic AMP in healthy and hypertensive pregnant women.
1. Platelet activation in vivo occurs in healthy pregnant women and is more marked in women with preeclampsia. During pregnancy platelets have also been shown in vitro to be less susceptible to the inhibitory effects of prostacyclin. The cyclic nucleotide cyclic AMP has a key role as an inhibitory second messenger in platelets and mediates the inhibitory effects of prostacyclin. 2. We have studied cyclic AMP in relation to platelet behaviour in healthy pregnant women in the third trimester and in women with pregnancy-induced hypertension and pre-eclampsia. Non-pregnant young women were used as controls. 3. Pharmacological agents which increase levels of cyclic AMP were significantly less effective as inhibitors of platelet activation during pregnancy, but there was no difference between the healthy and hypertensive pregnant subjects. 4. Basal platelet cyclic AMP levels were the same in all three groups. However, the production of cyclic AMP in response to a range of adenylate cyclase stimulators was reduced during pregnancy, but again there was no difference between healthy and hypertensive pregnant subjects. 5. The reduction in platelet cyclic AMP levels in pregnancy occurred not only with those adenylate cyclase stimulators which operate via surface receptors, but also on direct stimulation of the enzyme with forskolin. 6. The most likely explanation of these observations is a reduction in the ability of the platelet adenylate cyclase enzyme to respond to stimulation of the third trimester of pregnancy. The consequent reduction in formation of the inhibitory second messenger cyclic AMP may in part be responsible for platelet activation in vivo during pregnancy. There does not appear to be a further difference in platelet cyclic AMP production in hypertensive pregnant women.
Horn
E H
EH
Department of Therapeutics, University Hospital, Nottingham, UK.
Cooper
J
J
Hardy
E
E
Heptinstall
S
S
Rubin
P C
PC
D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D003430:Cross-Sectional Studies; D000242:Cyclic AMP / Q000096:biosynthesis / Q000097:blood*; D005260:Female; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D015539:Platelet Activation / Q000502:physiology; D011225:Pre-Eclampsia / Q000097:blood* / Q000378:metabolism; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D013929:Thromboxane B2 / Q000097:blood
D001095:Arachidonic Acids; D013929:Thromboxane B2; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D016285:Iloprost