15.5.79 Specialia 647 fused amounts reached 0.3-3.0 mg/kg. In rabbits with intact circulation (IC) acebutolol induced a significant decrease in heast rate; no significant effects upon mean blood pressure and peripheral resistance (table), and aortic blood flow were observed. By contrast, in all animals under TCB (at constant arterial reinjection frequency) we noted a decrease in mean blood pressure and peripheral resistance (table); aortic blood flow did not change significantly. A progressive increase in baroreceptor activity occurred immeeiately after the start of infusion of acebutolol in all experiments (IC or TCB). Reductions in renal nerve activi- ty were observed during infusion of acebutolol in rabbits with IC (-27.0+2.3%; n= 3 animals). Discussion. The present experiments show that acute i.v. administration of acebutolol in rabbits induced an increase m baroreceptor firing and decreased postganglionic sympa- thetic renal-nerve discharge. Blood pressure and calculated peripheral resistance were reduced under TCB in contrast with the results obtained in rabbits with IC. The increase in peripheral resistance observed under IC in some animals might result from a reflex response to the reduced cardiac output. This interpretation could be consistent with our Haemodynamic and baroreceptor responses to i.v. infusion of acebutolol (mean • SEM) Intact Total cardiopulmonary circulation by-pass Heart rate in - 17.7_+ 4.7 0 beats/min n = 7 (%) p<0.001 Mean blood - 6.0_+7.8 - 8.8+_3.5 pressure n = 7 n = 5 (mm Hg) NS p<0.01 Peripheral + 4.0 • 22.1 - 15.8 +_ 4.9 resistance in AU n = 4 n = 5 (%) NS p<0.01 Baroreceptor activity + 19.9_+ 4.2 + 14.4_+ 9.9 in counts/sec n = 7 n = 5 (%) p < 0.001 p < 0.05 n: Number of animals, NS: not significant, AU: arbitrary units. findings in TCB experiments, where a decrease in peripher- al resistance was constantly noted after drug. Sympathetic renal nerve activity was reduced by acebuto- lol. Similar results were obtained with ill- f12- adrenocep- tot-blocking agents 2~ and with another fll-adrenoceptor- blocking agent, atenolol< As observed with/?l- fl2-adrenoceptor-blocking agents, aor- tic baroreceptor firing was increased by acebutolol (and by atenolol; unpublished experiments) in spite of a diminished blood-pressure level. This increase in baroreceptor dis- charge was probably not caused by the vasodilation, which was not observed in all experiments. It is conceivable that the drug-induced change in aortic nerve activity could be due to an indirect effect mediated via central nervous effects on sympathetic nerve activity to the receptor area. Another possibility would be that inhibition of beta-adre- nergic tone by the drugs leads to some contraction of aortic smooth-muscle cells, mimicking the effects of sympathetic activity and noradrenaline upon the baroreceptor area. In conclusion it is noteworthy that all the fl-adrenoceptor- blocking agents studied (with common antihypertensive properties but with different pharmacological patterns) induced an increase in baroreceptor activity. This phenomenon may initiate or contribute to the reduction in sympathetic outflow described at the splanchnic 6,7 and at the post ganglionic 2-5 levels, 1 We wish to thank Mrs H. Bodard and Mrs F. Raimbault for their technical collaboration and Specia Laboratories for sup- plying acebutolol. This work was supported by a grant from INSERM (ATP No. 15.75.38). 2 A. Friggi, A.M. Chevalier-Cholat and J. Torresani, C.r. Acad. Sci. Paris 284, 1835 (1977). 3 A. Friggi, A.M. Chevalier-Cholat and J. Torresani, Eur. J. Pharmac. 45, 295 (1977). 4 A.M. Chevalier-Cholat, A. Friggi and J. Torresani, Biomedi- cine 28, 67 ((978). 5 A. Friggi, A.M. Chevalier-Cholat and H. Bodard, Experientia 33, 1207(1977). 6 P.J. Lewis and G. Haeusler, Nature 256, 440 (1975). 7 N.T. Daskalopoulos and H. Schmitt, Thdrapie 30, 843 (1975). Embryotoxicity and teratogenicity of Cis-diamminedichloroplatinum R. Lazar, P. C. Conran and I. Damjanov University of Connecticui Health Center, ~brmington (CT 06032, USA), and Hahnemann Medical College, Philadelphia (Pennsylvania 19102, USA), lO August 1978 Summary. Cis-diamminedichloroplatinum has lethal, toxic and teratogenic effects on presomitic mouse embryos in doses that are not toxic to adult animals. Cis-diamminedichloroplatinum (II) (DDP) is a new antitu- mor compound that has shown promising effects in preclin- ical and clinical trials 1. In addition to tumoricidal effects DDP has antimicrobial, immunosuppressive and mutagenic properties. In this paper we report that DDP is also extremely embryotoxic and teratogenic in the mouse. Material and methods. Timed-pregnant outbred Swiss Web- ster mice were injected i.p. with freshly dissolved DDP on day 8 of pregnancy. The day the vaginal plug was found was considered to be day 1. Animals were injected with DDP in a single dose of either 13, 8 or 3 mg/kg b.wt. Control animals were either not injected at all or injected with 0.5 ml of saline. Pregnant dams were sacrificed on the 18th day of pregnancy. The numbers of live and stillborn fetuses and early and late resorptions were recorded. Each fetus was weighed. All the fetuses were examined under a dissecting microscope. Every third fetus was fixed in etha- nol, cleared in glycerol and stained with alizarin red S for detection of skeletal anomalies. The experimental data were analyzed by use of Student's t-test. Results. The data on embryotoxicity of DDP are sum- marized in the table. No maternal death was observed in any of the experimental groups. The live fetuses born to DDP treated dams weighed less than the controls despite the fact that each pregnant uterus contained fewer viable fetuses and that this could have caused more weight gain in