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A dramatic 15-fold increase in uterine blood flow in pigs occurs during pregnancy in association with marked increases in uterine arterial (UA) diameter. This study was conducted to determine UA collagen and elastin content, diameter, alpha 1- and alpha 2-adrenergic receptor (AR) numbers, norepinephrine (NE) and in vitro reactivity to phenylephrine on d 0, 20, 50, 80 and 110 of pregnancy in the pig. Uterine arterial collagen content declined progressively throughout pregnancy (P less than .01), whereas the content of elastin remained constant from d 0 to d 80, then increased (P less than .05) from d 80 to d 110. The UA collagen to elastin ratio was correlated with UA diameter (r = -.69; P less than .01), which increased from 4.5 mm on d 0 to 9.0 mm on d 110. Uterine arterial alpha 1-AR numbers remained low and constant throughout pregnancy, consistent with its retained ability to contract in response to phenylephrine. Uterine arterial NE content declined (P less than .05) from d 20 to d 80 before increasing slightly to d 110. Uterine arterial alpha 2-AR numbers remained high from d 0 to d 80 before decreasing (P less than .05) to low values on d 110. These data are consistent with a reduced adrenergic neuronal control and increased elasticity of the UA during pregnancy in the pig.

The uterine paracervical ganglion (Frankenhauser's ganglion) contains the terminal ganglion cells of the sacral parasympathetic system and, in some species, the short adrenergic system. Histochemical studies also show numerous chromaffin cells with morphologic attributes of interneurons. The present study explores the function of cell types present in this ganglion, by seeking changes in reproductive function following either parasympathetic decentralization (transection of the cauda equina) or excision of the ganglion itself. Two well-known reproductive phenomena were observed after each surgical intervention, namely, induction of uterine hyperemia by estrogen administration, and maintenance of normal vaginal cycles. Estrogen-induced uterine hyperemia was not affected by parasympathetic decentralization or ganglion excision. Therefore, nerves originating in, or passing through this structure may be eliminated as components of the vascular control mechanism. In contrast, compared to sham-operated controls, ganglionectomy caused a significant reduction in the proportion of animals exhibiting normal vaginal cycles postoperatively (P less than 0.05). Cycle distribution was more evident in animals ganglionectomized on metestrus (P less than 0.01) and proestrus (P less than 0.05) than in animals ganglionectomized on diestrus or estrus. Since parasympathetic decentralization did not produce cycle disruption similar to ganglionectomy, one may conclude that the cycle-modulating effect does not involve preganglionic fibers of the sacral parasympathetic nerves.

Human cathepsin G is a serine proteinase with chymotrypsin-like specificity found in both polymorphonuclear leukocytes (neutrophils) and the U937 leukemic cell line. Utilizing RNA from the latter, we have constructed a cDNA library in lambda gt11 and isolated a clone which apparently codes for the complete amino acid sequence of this enzyme. Analysis of the sequence reveals homology with rat mast cell proteinase II (47%) but a greater degree of identity (56%) with a product of activated mouse cytotoxic T lymphocytes. The close relationship between the three proteins indicates similarities in substrate specificity and in biosynthesis which we predict involves removal of a two amino acid activation peptide during or just before packaging into their respective storage granules.

Phenylbutazone (Butazolidin), and anti-inflammatory agent, has been reported to decrease renal excretion of sodium and water. Whether or not an alteration in renal hemodynamics could be involved in producing these effects was tested in anesthetized dogs. Renal blood flow (RBF) was monitored with electromagnetic flow probes. After i.v. administration of phenylbutazone, 2 mg/kg, RBF fell by 20%. Glomerular filtration rate, sodium and water excretion were also decreased and blood pressure increased slightly. The reduction of RBF and glomerular filtration rate by phenylbutazone indicates that a hemodynamic mechanism could be involved in the retention of sodium and water induced by this agent. The decreased blood flow was correlated with a depressed renal secretion of prostaglandin E. Also, in animals pretreated with indomethacin, another inhibitor of prostaglandin synthesis, administration of phenylbutazone did not result in any additional changes in renal hemodynamics or excretion of sodium and water. In addition, phenylbutazone antagonized the ability of furosemide to increase RBF, an inhibition which has previously been shown to occur with indomethacin. Thus, phenylbutazone appears to alter renal mechanisms in a manner similar to indomethacin.

The human U937 cell line, a promonocyte-like leukemic line, has been shown to synthesize neutrophil elastase (Senior, R. M. et al. (1982) J. Clin. Invest. 69, 384-393). We have constructed a lambda gt11 cDNA library using RNA from this cell line and isolated a clone encoding part of the protein sequence of neutrophil elastase. Nucleotide sequencing indicates the clone encodes residues 108-243 (standard chymotrypsinogen numbering) of the enzyme, plus a hitherto unsuspected 20 residue-C-terminal extension of unusual structure. Comparison of the nucleotide and amino-acid sequence of elastase with the recently reported sequence of medullasin, a proteinase isolated from bone marrow, suggests they are identical.

A method for constructing miniaturized Doppler blood flow probes is presented. Since these probes weigh less than 100 mg and have crystal heads less than 0.5 mm in size, they are suitable for chronic placement on vessels as small as 200 micron. The probes are positioned under the vessel and rotated to optimize the Doppler signal. While held in that position, the crystal head is attached to the adventitia of the vessel with cyanoacrylate glue. A cuff holding the vessel and probe in the chosen position is then formed in situ by the application of a drop of silicone polymer. Data are presented showing the linearity of a flow probe response with the volume blood flow at rates as low as 14 microliter/min. With the use of the uterine artery of the conscious, unrestrained rat as an example, the probe was demonstrated to detect a dynamic change in flow.