: The effects of pinacidil and nimodipine on endothelin‐1‐induced contractions in isolated cerebral arteries with and without endothelium were compared. The sensitivity to endothelin‐1 was increased ...(0.5 log units) in the rabbit basilar artery after removal of the endothelium. The nitric oxide synthase inhibitor Nω‐nitro‐L‐arginine (0.1 mM) also increased the sensitivity to endothelin‐1 (0.6 log units) in basilar arteries with endothelium, whereas Nω‐nitro‐D‐arginine (0.1 mM) and indomethacin (3 μM) had no effect, indicating that withdrawal of endothelium‐derived nitric oxide may account for the enhancement of the endothelin‐1‐induced contraction after endothelial denudation. Pinacidil (1 μM) shifted the concentration‐response curve for endothelin‐1 to the right without affecting the maximal response in arteries without endothelium, but had no effect on the endothelin‐1‐induced contraction in vessels with endothelium. Nimodipine (1 μM) reduced the maximal endothelin‐1‐induced contraction by approximately 50% in both the presence and absence of endothelium, whereas the sensitivity to endothelin‐1 was reduced only in vessels without endothelium. Incubation in "calcium‐free" medium reduced the maximal endothelin‐1‐induced contraction by 69% and 80% in vessels with and without endothelium, respectively. In human pial arteries with endothelium, pinacidil did not affect the endothelin‐1‐induced contraction, whereas nimodipine and exposure to "calcium‐free" solution reduced the maximal response by 31% and 74%, respectively. The results show that, in the rabbit, pinacidil and to a lesser extent nimodipine preferentially act on cerebral arteries with disrupted endothelium, indicating that vasoactive factors liberated from the endothelium may modify the effect of a vasodilator.
The materno-fetal transfer of methionine in the Rhesus monkey was investigated using positron emission tomography, a non-invasive in vivo tracer technique based on short-lived radionuclides. A bolus ...dose of 11CH3-l-methionine was administered intravenously and the radioactivity concentrations in the placenta, the fetus and the maternal arterial blood were measured as functions of time and fitted to an equation derived from a four compartment model of the feto-placental complex. Rate constants were calculated describing maternal placental blood flow, the transfer of 11CH3-l-methionine to the placental tissue and the fetus. The transfer rate of methionine to the fetus was estimated as 0.8-1.5 nmol/min/g placenta and was similar to the transfer to the placental tissue. An approximate blood flow through the intervillous space of 128 ml/min was found. The correlation between placental transfer to the fetus and the maternal blood flow in the intervillous space was low.
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