In vitro production of prostaglandins by isolated aorta strips of normotensive and hypertensive rats.

When suspended in oxygenated Krebs solution at 37 degrees C, strips derived from thoracic aortae of spontaneously hypertensive rats maintain their initial intrinsic tone and release prostaglandin-like material in the suspending medium, while similar preparations from normal Wistar rats relax progressively and produce significantly smaller amounts of prostaglandins. Indomethacin, a potent antagonist of prostaglandin synthesis, has two major effects: it favors the relaxation of both strips of hypertensive rats and of normal rats; and it inhibits the accumulation of prostaglandin-like material in the suspending medium, as evaluated with a specific and sensitive biological assay (rat stomach strip or chick rectum). Carotid and femoral arteries taken from the same animals show similar differences as the aorta strips, with regard to the production of prostaglandin-like material. The generation of prostaglandin is markedly decreased by the absence of O2, while it is unaffected by the absence of the extracellular Ca2+. It is proposed that the absence of relaxation of aorta strips taken from hypertensive, compared to normal rats, is due to increased intramural synthesis and release of prostaglandins.     

Binding of [3H]des-Arg9-BK to rabbit anterior mesenteric vein

Binding studies of [3H]des-Arg9-BK have been performed on pieces of rabbit anterior mesenteric veins. Kinetic studies have permitted us to evaluate an affinity constant of 1.04 X 10(-7) M, which is not so different from the apparent affinity constant determined by bioassay (1.6 X 10(-7) M). Furthermore, inhibition of the binding of [3H]des-Arg9-BK with various kinins results in an order of potency of kinins very similar to that observed in the bioassay. Taken together, these results suggest that we are dealing with binding sites which might be the same as those subserving the biological action of des-Arg9-BK (pharmacological receptors). The preincubation of tissues in Krebs' solution brings about an increase of the specific binding from 0.06 pmol/mg of wet weight at time 0 to 0.75 pmol after 24 h; cycloheximide inhibits this increase for at least 6 h. Veins taken from animals treated with LPS, which have shown an increase in sensitivity compared with veins extracted from untreated animals, have a higher number of specific binding sites for [3H]des-Arg9-BK. The results support the hypothesis that the increased response of tissues to des-Arg9-BK is due to the de novo synthesis of receptors for kinins in some experimental and pathological conditions.