ABSTRACT
Urinary excretion of thromboxane B2 metabolites as markers of thromboxane A2 synthesis was measured in eight patients with moderate to severe pregnancy-induced hypertension and in six normotensive pregnant women at term. Excretion of both 2,3-dinor-TxB2 (median 3919, range 683-16,680 pg/mg creatinine) and 11-dehydro-TxB2 (median 10,187, range 434-57,203 pg/mg creatinine) was significantly higher in the patients with pregnancy-induced hypertension than in the normotensive pregnant group (927[273-1343] and 774[500-2760] pg/mg creatinine, respectively). Thromboxane metabolite excretion correlated with mean arterial blood pressure, plasma lactate dehydrogenase, and platelet count which are indices of the severity of pregnancy-induced hypertension. Excretion of both metabolites fell rapidly post partum in parallel with resolution of clinical signs. Thus, increased thromboxane A2 biosynthesis correlates with disease severity and may have a pathogenetic role in pregnancy-induced hypertension. These findings provide a rationale for the use of aspirin in the treatment as well as in the prevention of this disorder.
Subject(s)
Hypertension/metabolism , Pregnancy Complications, Cardiovascular/metabolism , Thromboxane A2/biosynthesis , Adolescent , Adult , Aspirin/therapeutic use , Evaluation Studies as Topic , Female , Humans , Hypertension/blood , Hypertension/prevention & control , Hypertension/urine , Platelet Activation/drug effects , Platelet Activation/physiology , Platelet Count/drug effects , Pregnancy , Pregnancy Complications, Cardiovascular/blood , Pregnancy Complications, Cardiovascular/prevention & control , Pregnancy Complications, Cardiovascular/urine , Severity of Illness Index , Thromboxane B2/analogs & derivatives , Thromboxane B2/urineABSTRACT
Several N-allyl derivatives of 1-phenylcyclohexylamine (PCA) were prepared, and their pharmacology was briefly characterized. The mono- and diallyl derivatives had phencyclidine-like activities in mice but were less potent behaviorally than phencyclidine (PCP). None were PCP antagonists. In vitro these compounds were competitive inhibitors of butyrylcholinesterase (BChE) and protected against inhibition by DFP. In addition, these agents displaced tritiated N-methyl-4-piperidyl benzilate from mouse-brain homogenates and inhibited the effects of acetylcholine on isolated guinea pig ileum. None of these in vitro effects correlated with their PCP-like behavioral activity in vivo in mice.
Subject(s)
Phencyclidine/analogs & derivatives , Phencyclidine/pharmacology , Animals , Brain/metabolism , Butyrylcholinesterase , Chemical Phenomena , Chemistry , Cholinesterase Inhibitors/pharmacology , Drug Interactions , Guinea Pigs , Horses , Ileum/drug effects , Isoflurophate/pharmacology , Male , Mice , Mice, Inbred ICR , Motor Activity/drug effects , Muscle Contraction/drug effects , Phencyclidine/chemical synthesis , Phencyclidine/toxicity , Rats , Rats, Inbred Strains , Receptors, Muscarinic/drug effects , Structure-Activity RelationshipABSTRACT
The effects of stretching and of prostaglandin F2alpha on spontaneous and induced with local deformation contractile activity of rat uterus were studied. It was found that stretching the uterus up to the length of the decontracted organ in vivo increased the contractile and bioelectric activity. The rise in spontaneous uterine activity was a factor reducing induction of additional contractions. The fall in the level of endogenous prostaglandins in the uterus following administration of indomethacin inhibited the spontaneous contractile activity but was without effect on the contractions induced by local deformation of the myometrium. Prostaglandin F2alpha added to the bath in a concentration of 0.001 ng/ml exerted an inhibitory action on the different tested parameters of the contractile activity. After high doses stimulation of the uterine activity was observed.