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Several studies have suggested that clonidine, guanfacine and rilmenidine decrease systemic blood pressure by stimulating central alpha 2-adrenergic receptors. However, we have shown that these molecules interact not only with alpha 2-adrenergic but also a new type of "non catecholamine" receptor in rabbit and human renal proximal tubules. This receptor, which we have called the imidazoline-guanidium receptor site (IGRS) seems to be pharmacologically, biochemically and fractionally distinct from alpha 2-adrenergic receptors. In order to determine the relative affinity of rilmenidine for these two types of receptor, we studied its capacity to inhibit the liaison of (H3)-idazoxan, a ligand with a high affinity for the IGRS, and of (H3)-rauwolscine, a ligand selective for alpha 2-adrenergic receptors in the rabbit kidney. The results based on the apparent constants of inhibition (Ki) of the two radioligands [231 +/- 34 nM for (H3)-idazoxan and 2440 +/- 322 nM for (H3)-rauwolscine] showed that the selectivity of rilmenidine was 10 times greater for IGRS than for alpha 2-adrenergic receptors. This preferential activity on IGRS was confirmed by studies of the influx of Na22 into isolated renal proximal tubule cells of the rabbit. They showed that rilmenidine, in contrast to catecholamines, inhibited the transport of Na22 into the renal cells. In conclusion, the data from our studies shows that rilmenidine interacts with renal IGRS and inhibits cellular transport of sodium by a mechanism other than the stimulation of alpha 2-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA immunization is a common complication of transfusion therapy in 30% to 60% of oncohematologic patients. Evidence shows that leukocytes present in cellular blood products are the main component involved in the occurrence of HLA immunization, and several studies showed that leukocyte-poor blood products are less able to induce it. However, leukocyte-poor platelet concentrates obtained by conventional techniques, ie, centrifugation, frequently have a high level of remaining leukocytes. Cotton wool filter Imugard IG 500 can be used to obtain leukocyte-poor cellular blood products. The technique is easy to perform, even in an emergency, and can be used with either packed RBCs or platelet concentrates. Means of 97%, 92%, and 76% elimination of leukocytes are obtained for packed RBCs, pooled standard platelet concentrates, and single-donor platelet concentrates, respectively. Patients were randomized to receive either standard (control group) or filtered (leukocyte-poor group) blood products. Of 112 randomized patients, 69 were evaluable, 35 in the control group and 34 in the leukocyte-poor group. Both groups are comparable according to age, diagnosis, sex ratio, previous transfusions, and pregnancies. There is a significant difference in regard to the HLA immunization rate (31.4% in the control v 11.7% in the leukocyte-poor group, P less than .05) and frequency of refractoriness to platelet transfusions (46.6% v 11.7%, P less than .05). We conclude that this filtration technique can be an efficient means to reduce the HLA immunization rate in polytransfused oncohematologic patients.

Isolated proximal cells were prepared from rabbit kidney cortex by mechanical dissociation. The intracytoplasmic pH (pHi) was measured in HCO3(-)-free media (external pH (pHe), 7.3) using the fluorescent dye 2,7-biscarboxyethyl-5,6-carboxyfluorescein (BCECF). Cells were acid-loaded by the nigericin technique. Addition of 70 mM Na+ to the cells caused a rapid pHi recovery, which was blocked by 0.5 mM amiloride. When the cells were exposed to 5 mM sodium butyrate in the presence of 1 mM amiloride, the H+ efflux was significantly increased and followed Michaelis-Menten kinetics. Increasing pHe from 6.4 to 7.6 at a constant pHi of 6.4 enhanced the butyrate activation of the H+ efflux. Increasing pHi from 6.5 to 7.2 at a constant pHe of 7.2 reduced the butyrate effect. 22Na uptake experiments in the presence of 1 mM amiloride showed that 1.5 mM butyrate increased the Na+ flux in the proximal cells (pHi 7.10). The efficiency of monocarboxylic anions in promoting a pHi recovery increased with the length of their straight chain (acetate less than propionate less than butyrate less than valerate). The data show that when the Na+/H+ antiporter is blocked, the proximal cells can regulate their pHi by a Na+-coupled absorption of butyrate followed by non-ionic diffusion of butyric acid out of the cell and probably also by OH- influx by means of the OH-/anion exchanger.