Prostanoids are the cyclooxygenase metabolites of arachidonic acid and include prostaglandin (PG) D2, PGE2, PGF2α, PGI2, and thromboxne A2. They are synthesized and released upon cell stimulation and act on cells in the vicinity of their synthesis to exert their actions. Receptors mediating the actions of prostanoids were recently identified and cloned. They are G protein-coupled receptors with seven transmembrane domains. There are eight types and subtypes of prostanoid receptors that are encoded by different genes but as a whole constitute a subfamily in the superfamily of the rhodopsin-type receptors. Each of the receptors was expressed in cultured cells, and its ligand-binding properties and signal transduction pathways were characterized. Moreover, domains and amino acid residues conferring the specificities of ligand binding and signal transduction are being clarified. Information also is accumulating as to the distribution of these receptors in the body. It is also becoming clear for some types of ...

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Prostanoid Receptors: Structures, Properties, and Functions

Blood flow measurements with radionuclide-labeled particles.

The alterations in myocardial energy substrate metabolism that occur in heart failure, and the causes and consequences of these abnormalities, are poorly understood. There is evidence to suggest th...

/pdf/myocardial-substrate-metabolism-in-the-normal-and-failing-1cql6lgwxf.pdf

Myocardial Substrate Metabolism in the Normal and Failing Heart

Prospective Trial of Supranormal Values of Survivors as Therapeutic Goals in High-Risk Surgical Patients

Nonsteroidal anti-inflammatory drugs (NSAIDs) represent one of the most highly utilized classes of pharmaceutical agents in medicine. All NSAIDs act through inhibiting prostaglandin synthesis, a catalytic activity possessed by two distinct cyclooxygenase (COX) isozymes encoded by separate genes. The discovery of COX-2 launched a new era in NSAID pharmacology, resulting in the synthesis, marketing, and widespread use of COX-2 selective drugs. These pharmaceutical agents have quickly become established as important therapeutic medications with potentially fewer side effects than traditional NSAIDs. Additionally, characterization of the two COX isozymes is allowing the discrimination of the roles each play in physiological processes such as homeostatic maintenance of the gastrointestinal tract, renal function, blood clotting, embryonic implantation, parturition, pain, and fever. Of particular importance has been the investigation of COX-1 and -2 isozymic functions in cancer, dysregulation of inflammation, and Alzheimer's disease. More recently, additional heterogeneity in COX-related proteins has been described, with the finding of variants of COX-1 and COX-2 enzymes. These variants may function in tissue-specific physiological and pathophysiological processes and may represent important new targets for drug therapy.

Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition

Techniques are described for insertion of vinyl catheters into the umbilical and limb vessels of the fetus of the sheep or the goat through small uterine incisions, with the ewes under spinal analg...

https://www.ahajournals.org/doi/pdf/10.1161/01.RES.21.2.163

The Circulation of the Fetus in Utero METHODS FOR STUDYING DISTRIBUTION OF BLOOD FLOW, CARDIAC OUTPUT AND ORGAN BLOOD FLOW

Cardiovascular responses to hypoxemia and acidemia in fetal lambs.

The changes in circulation with advancing gestation were investigated in 44 fetal lambs in utero; gestational ages ranged from about 60 days to 150 days. Spinal analgesia was administered to the ewe, polyvinyl catheters were inserted into fetal vessels, and umbilical blood flow was measured by the steady-state diffusion Fick method during antipyrine infusion. Cardiac output, distribution of cardiac output, and actual organ blood flows were calculated from injections of nuclide-labeled microspheres (50µ diam) into a forelimb and into an umbilical or hindlimb vein. Umbilical Po 2 , Pco 2 and pH did not change significantly during gestation. Umbilical blood flow and total cardiac output increased in proportion to fetal weight. The proportion of the combined ventricular output distributed to the placenta decreased from about 50% in the youngest fetuses to about 40% just before term. The proportion of the cardiac output distributed to the lungs, as well as the actual flow in relation to lung weight, increased throughout gestation, with a more rapid rise after about 120 days. There was also a late increase in intestinal flow. Cerebral blood flow increased gradually throughout gestation, both as a proportion of cardiac output and in relation to brain weight. There were no significant changes in percent of cardiac output, or flow related to weight in the kidney, heart, or skin and muscular tissues. The studies suggest that, since lung blood flow is a relatively small proportion of total cardiac output, it is not important in regulating distribution of blood flow, but that the peripheral circulation in skin and muscle, which receives a large percent of fetal cardiac output, is the site where vasomotor responses may effect major redistribution of the fetal circulation.

Circulatory Changes during Growth in the Fetal Lamb

Inhibition of prostaglandin synthesis constricts the ductus arteriosus in fetal lambs in utero. We administered the inhibitors, aspirin or indomethacin to 18 premature infants with patent ductus arteriosus, and assessed the effects clinically and by echocardiography (left atrial/aortic-root ratio). After aspirin (20 mg per kilogram, every six hours for four doses) the ductus closed permanently in one infant within 24 hours; in another, constriction occurred with clinical improvement, and the third did not respond. In five infants given 0.3 mg per kilogram of indomethacin, complete closure occurred within one day; two of them, who received three doses had an elevated serum creatinine for one week. In one infant the ductus reopened, requiring a second dose of indomethacin 11 days after the first. Ten infants received 0.1 mg per kilogram of indomethacin, and closure occurred within 24 to 30 hours in eight. One had a soft murmur for four days, and one did not respond to two doses of indomethacin. A murmur reappeared after three to seven days in three infants but only one required further treatment. In infants receiving a single dose of 0.3 mg per kilogram, or one or more doses of 0.1 mg per kilogram, renal function was unaltered.

https://www.nejm.org/doi/pdf/10.1056/NEJM197609022951004?listPDF=true

Abraham M. Rudolph

Papers

Blood flow measurements with radionuclide-labeled particles.

The Circulation of the Fetus in Utero METHODS FOR STUDYING DISTRIBUTION OF BLOOD FLOW, CARDIAC OUTPUT AND ORGAN BLOOD FLOW

Cardiovascular responses to hypoxemia and acidemia in fetal lambs.

Circulatory Changes during Growth in the Fetal Lamb

Closure of the Ductus Arteriosus in Premature Infants by Inhibition of Prostaglandin Synthesis