Centrally administered ANF promotes appearance of a circulating sodium pump inhibitor.

We have previously reported that release of an endogenous Na pump inhibitor, a putative natriuretic hormone associated with many hypertensive states, may be regulated by the central nervous system (CNS). The atrial natriuretic factor (ANF), which causes diuresis, vasorelaxation, and inhibition of aldosterone and vasopressin release, has been documented in the CNS as well as the atria and peripheral blood. Our experiments investigate the possible interaction of ANF with a circulating specific inhibitor of the Na pump in normal rats. The Na pump inhibitory capacity of plasma from rats previously injected with either [Arg101-Tyr126]ANF or vehicle into the lateral cerebral ventricle was measured in cultured aortic smooth muscle cells (ASMC) using 86Rb uptake methodology. Plasma from rats injected with ANF inhibited the Na pump activity (18 +/- 4%, n = 4 experiments) in ASMC compared with plasma obtained from rats injected with the vehicle. The nonspecific 86Rb uptake was not affected by the ANF treatment. Plasma obtained from rats injected intravenously with ANF did not affect the Na pump activity in the ASMC. Furthermore, ANF did not directly affect Na pump activity in ASMC when added to the culture dishes in vitro. These findings raise the possibility that central ANF regulates the release of circulating Na pump inhibitor.

Pre-incubation of human monocytes results in loss of effector activity and diminished stimulation of the autologous mixed lymphocyte reaction.

Human monocytes were cultured at 37 degrees C for 72 h, washed, adjusted for viability and compared to freshly prepared monocytes for stimulation of the autologous mixed lymphocyte reaction (AMLR) and effector function. Pre-incubated monocytes were less potent AMLR stimulators than were freshly prepared cells. Pre-incubated monocytes demonstrated less antibody-dependent tumour killing of CCRF-CEM, less killing of Staphylococci and less spontaneous tumour killing of K-562 than did fresh monocytes. Pre-incubated monocytes produced less prostaglandin E2, demonstrated less surface Ia antigen and were less efficient accessory cells for antigen presentation than were fresh monocytes. AMLR stimulation correlated with monocyte killing (r = 0.95) and PGE2 production (r = 0.98). Thus, monocytes pre-incubated for 3 days are less active effector cells, display less surface Ia antigen and are less potent stimulators of the AMLR than fresh monocytes. Moreover, in this system, monocyte effector activity correlates with ability to stimulate the AMLR.

Estradiol and tamoxifen stimulation of lapine articular chondrocyte prostaglandin synthesis.

The effect of estradiol and tamoxifen on prostaglandin (PG) synthesis by rabbit articular chondrocytes in secondary monolayer cultures was investigated. Radioimmunoassay for PGE2, PGF2 alpha, 6-oxo-PGF1 alpha and thromboxane B2 was performed on media from cultures containing estradiol and tamoxifen (10-12M-10-7M). Radiometric thin-layer chromatography was also carried out. The time course of estradiol/tamoxifen effect on chondrocyte PG synthesis was evaluated and its relationship to cell density in culture examined. Estradiol stimulated the synthesis of PGs by chondrocytes. Stimulation was noted at picomolar concentrations of estradiol without further stimulation at markedly higher concentrations. In time studies, after a lag, the effect of estradiol was present fully by 5 hrs, remained steady for 24 hrs and then declined by 48 hrs. Estradiol stimulation of PG synthesis was dependent upon chondrocyte culture plating density. Tamoxifen stimulated chondrocyte PG synthesis to relatively lower levels than estradiol. The characteristics of estradiol/tamoxifen stimulation of chondrocyte PG synthesis suggest a mechanism involving estradiol cytoplasmic receptors.