The purposes of our study were to determine the contribution of the CNS to the hypotensive effect of urapidil in the cat and the specific brain site of action of this agent. For the first purpose, ...urapidil was studied on preganglionic sympathetic nerve activity, arterial pressure, and heart rate. Three systemic bolus doses of urapidil were administered (0.22, 0.44, and 1.3 mg/kg). All three doses lowered arterial pressure, and the highest dose produced a significant decrease in sympathetic nerve discharge in five of six animals studied. The lower two doses had no significant effect on sympathetic activity, and none of the doses altered heart rate. These results suggest that a high i.v. dose of urapidil is required to evoke hypotension by an action in the central nervous system (CNS). For the second purpose, urapidil was applied bilaterally to the intermediate area of the ventral surface of the medulla in doses of 25 and 50 µg. These doses caused decreases in arterial pressure of −6.1 ± 2.2 (p < 0.05) and −21.0 ± 5.9 (p<0.05) mm Hg, respectively, but no change in heart rate. In addition, respiratory stimulation also occurred with the higher dose as respiratory minute volume increased by 81 ± 14 ml/min (p < 0.05). The highest dose of urapidil had no effect on arterial pressure when applied to other chemosensitive areas of the ventral surface of the brain. Comparative studies with prazosin (10 µg applied bilaterally to the intermediate area) indicated no hypotensive effect of this α1-adrenoceptor blocking agent. These results suggest that the central hypotensive effect of urapidil occurs at the intermediate area and does not involve blockade of α1-adrenoceptors.
In addition to allowing for the long-term culture of both murine and human cytolytic T lymphocytes, T-cell growth factor (TCGF) functions as the key proliferation-inducing second signal in both ...T-cell antigen sensitization and mitogenesis. The observation that thymocytes responded normally to T-cell mitogens in the presence of TCGF, prompted the investigation of the effect of TCGF on nude mouse lymphocyte responses in vitro. We found that spleen, lymph node, and bone marrow cells, isolated from nude mice, were incapable of producing TCGF yet responded normally to T-cell mitogen sensitization provided stimulation was conducted in the presence of TCGF. Nude mouse spleen cells were also capable of responding to alloantigen sensitization in mixed lymphocyte cultures (NLMC) conducted in the presence of TCGF. Thy-1 antigen-positive cells harvested from TCGF-supplemented nude mouse MLC effectively mediated the cytolysis of alloantigen-specific target cells as tested in standard 51Cr-release assays. Cytolytic nude mouse effector cells have remained in TCGF-dependent culture for over 3 mo during which they have continued to mediate significant levels of alloantigen-specific cytolytic reactivity. These results suggest that prothymocytes present in nude mice are capable of responding to immunologic stimuli by differentiating, in vitro, into cytolytic T lymphocytes and that furthermore, a major function of the thymus may be to effect the maturation of TCGF-producing cells.
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