Alpha 1-adrenoreceptor blockade reduces the angiotensin II-induced vascular smooth muscle cell DNA synthesis in the rat thoracic aorta and carotid artery.

We explored effects of alpha 1-adrenoreceptor blockade with prazosin on the increased vascular smooth muscle cell (SMC) DNA synthesis induced by angiotensin II (Ang II) in rats. Ang II was infused with or without prazosin or its solvent. Observations were compared with those in rats receiving saline or solvent. In group A, Ang II was infused for 2 weeks by subcutaneously implanted osmotic minipumps at a rate of 35 ng/100 g per minute. Group B received Ang II together with the alpha 1-adrenoreceptor antagonist prazosin (0.35 micrograms/100 g per minute). Group C received Ang II and 50% dimethyl sulfoxide (DMSO), the solvent of prazosin; group D received 50% DMSO; and group E received 0.9% NaCl (Ang II vehicle). All animals were infused with 5-bromo-2'-deoxyuridine for 2 weeks via separate minipumps to measure DNA synthesis. Ang II significantly increased the fraction of DNA synthesizing SMCs in the media of the thoracic aorta from 0.4 +/- 0.1% (mean +/- SD) in group E (n = 6) to 10.8 +/- 7.0% in group A (n = 8). Addition of prazosin to Ang II reduced the labeling fraction of SMCs to 3.0 +/- 2.2% (group B, n = 9). The remaining SMC DNA synthesis in the prazosin-treated group was probably due to the effects of the solvent of prazosin, i.e., 50% DMSO, since infusion of 50% DMSO alone increased the labeling fraction to 4.1 +/- 2.0% (group D, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of ischemia due to "steal" by arteriovenous fistula with distal artery ligation and revascularization

Three cases are described of upper extremity ischemia occurring after the creation of fistulas (AVFs) (one case) and bridge AVFs (two cases) for hemodialysis access. All three cases were successfully treated with ligation of the artery immediately distal to the origin of the AVF in conjunction with a reversed saphenous vein bypass. The latter was constructed from the artery proximal to the origin of the fistula to the artery distal to the site of ligation. Preoperative and postoperative hemodynamic measurements and complete disappearance of symptoms indicated that this procedure corrected the ischemic steal phenomenon. Angioaccess function was not affected in these three cases, thereby allowing continuation of its use immediately after corrective surgery and for follow-up periods of 1 month, 6 months, and 8 years.     

Inhibition of inward K+ channels and stomatal response by abscisic acid: an intracellular locus of phytohormone action.

Abscisic acid (ABA), a plant hormone whose production is stimulated by water stress, reduces the apertures of stomatal pores in the leaf surface, thereby lessening transpirational water loss. It has been thought that inhibition of stomatal opening and promotion of stomatal closure by ABA are initiated by the binding of extracellular ABA to a receptor located in the guard-cell plasma membrane. However, in the present research, we employ three distinct experimental approaches to demonstrate that ABA can act from within guard cells to regulate stomatal apertures. (i) The extent to which ABA inhibits stomatal opening and promotes stomatal closure in Commelina communis L. is proportional to the extent of ABA uptake, as assayed with [3H]ABA. (ii) Direct microinjection of ABA into the cytoplasm of Commelina guard cells precipitates stomatal closure. (iii) Application of ABA to the cytosol of Vicia faba L. guard-cell protoplasts via patch-clamp techniques inhibits inward K+ currents, an effect sufficient to inhibit stomatal opening. These results demonstrate an intracellular locus of phytohormone action and imply that the search for hormone receptor proteins should be extended to include intracellular compartments.     

Erythrocyte glutathione peroxidase activity in asthmatic children

Erythrocyte glutathione peroxidase (GPX) levels were determined in 56 asthmatic children. Lowest levels were found during acute asthmatic attack (13.53 +/- 2.94 IU) which were significantly less than controls (20.4 +/- 5.44 IU) (P less than .001). Post-attack levels 1 week later rose significantly (16.77 +/- 2.63 IU), but were still less than normal values (P = .001). GPX levels (16.96 +/- 3.28 IU) were less than controls (P less than .03) even in patients with mild symptomatology. Asymptomatic patients receiving theophylline had normal levels. Low GPX activity in asthmatic patients may play a role in the pathogenesis of the disease.     

Expression and characterization of glutathione peroxidase activity in the human blood fluke Schistosoma mansoni.

Antioxidants may play an important role in immune evasion by schistosome parasites. Previous studies have focused on the roles of superoxide dismutase and glutathione S-transferase. In the present study, glutathione peroxidase (GPX) activity was measured in different fractions of worm extracts from several developmental stages of Schistosoma mansoni. The enzyme activity was shown to be developmentally regulated, with higher specific activities being found in the tegument-enriched Nonidet P-40 extract of adult worms (the stage least susceptible to immune killing) than in the larval stages (which are most susceptible to immune elimination). In all extracts tested, the activity against cumene hydroperoxide, even when glutathione S-transferase activity was removed, was higher than that for hydrogen peroxide. The expression of GPX cDNA in pGEX-2T by bacteria produced a 50-kDa fusion protein and a 32-kDa truncated protein. The latter was due to termination at the internal UGA codon that codes for selenocysteine. GPX activity was detected in the recombinantly produced GPX but not with Sj26-glutathione S-transferase from the vector. Mutating the TGA codon to TGT produced a full-length product, GPXm (19 kDa), that was used to produce 19 monoclonal antibodies. Anti-GPXm monoclonal antibodies recognized a 19-kDa molecule in adult-worm extract which, upon removal by immunoprecipitation, resulted in the loss of over 90% of the GPX activity, suggesting that a single form of GPX exists in the schistosome.