Bradykinin stimulation of oxidative metabolism in renal cortical tubules from rabbit. Possible role of arachidonic acid.

Vasoactive peptides may have direct effects on both renal vasculature and renal tubules. In this study, we examined the direct and immediate effects of bradykinin on oxygen consumption by suspensions of cortical tubules from rabbit kidney. Bradykinin (10(-11) to 10(-7) M) stimulated oxygen consumption rates (QO2) in a dose-dependent manner with a maximal increase of +0.80 +/- 0.13 nmol X mg protein-1 X min-1. This stimulation was prevented by calcium-free media or by the addition of inhibitors of calcium transport, calcium-calmodulin complex formation, Na,K-ATPase activity, mitochondrial respiration, and phospholipase activity. Addition of bradykinin increased the ADP and AMP contents of cortical tubules without changing the ATP content. These data indicate that bradykinin stimulates ATP use and Na,K-ATPase activity. We also examined the effects of exogenous arachidonic acid on QO2 in cortical tubules. Acute additions of arachidonic acid stimulated QO2 at low concentrations (10(-8) to 10(-6) M) and uncoupled mitochondrial respiration at high concentrations (10(-5) M). The effect of arachidonic acid on adenosine nucleotide content was dose-dependent and indicated increased use of ATP. Bradykinin increased QO2 in the presence of low concentrations of arachidonic acid (10(-11) to 10(-9) M), but had no further effect on QO2 in the presence of higher concentrations of arachidonic acid (10(-8) to 10(-6) M). Bradykinin stimulation of QO2 was not prevented by inhibition of cyclooxygenase activity with indomethacin but was prevented by inhibition of lipoxygenase-like activity with nordihydroguariaretic acid. These results suggest that the bradykinin effect on QO2 may be mediated by arachidonic acid release and subsequent metabolism.

'Diaphragmlike' stricture and ulcer of the colon during diclofenac treatment.

Diclofenac sodium is a widely used enteric-coated nonsteroidal anti-inflammatory drug. We describe a woman with Hemoccult-positive stools and iron deficiency anemia who developed both a colonic ulcer and a "diaphragm-like" colonic stricture while taking enteric-coated diclofenac. These lesions were evident on colonoscopy but not on barium studies. Biopsy specimens of the ulcer and stricture revealed particulate matter that was indistinguishable from diclofenac pill fragments by electron microscopy. Discontinuation of diclofenac therapy resulted in resolution of anemia and Hemoccult-positive stools. We conclude that (1) enteric-coated diclofenac is associated with both colonic ulcers and diaphragm-like colonic strictures; (2) the pathophysiologic mechanism for the development of both ulcers and strictures may involve a direct action of diclofenac within these lesions; (3) colonoscopy may be superior to barium studies in evaluating patients receiving diclofenac who have iron deficiency anemia and/or Hemoccult-positive stools.

An objective measure of stool color for differentiating upper from lower gastrointestinal bleeding.

Subjective reporting of the color of blood passed per rectum has been used to predict the location of gastrointestinal bleeding, but the validity of this clinical approach has never been evaluated systematically. In this study we determined the spectrum of patient and physician descriptors used to characterize the color of blood passed per rectum and evaluated prospectively if an objective test of stool color would correlate with or improve upon subjective descriptions in predicting bleeding locations. The objective test employed was a card containing five numbered colors that typify the spectrum of stool blood colors. One hundred twenty patients used 23 different descriptors or terms to verbalize the color of blood they passed per rectum, and in 22% of cases there was a seeming discrepancy between their verbalized color and the color they pointed to on the test card. Patients pointing to card color 4 (the black color) resulted in closer matching to an upper bleeding source than physicians using terminology such as melena or tarry stools. Likewise, patients picking card colors 1 and 2 (the brightest red colors) resulted in closer matching to a coloanorectal bleeding source than physicians using the terms hematochezia or bright red blood per rectum (P < 0.02 for each comparison). The positive predictive value of card color 4 for an upper bleeding source was very high both when patients pointed to this color or when it was determined from the available stool (0.95 and 0.98, respectively). The positive predictive value of card color 1 for lower bleeding was greater for patients selecting this color than for a direct stool comparison (1.00 vs 0.83).(ABSTRACT TRUNCATED AT 250 WORDS)