1 The central hypotensive activity of (+)-and (-)-propranolol (100 ig), pindolol (100 ig) and isoprenaline (1 and 4 pg) injected intracerebroventricularly (i.c.v.) was studied in rats anaesthetized with urethane and chloralose. Blood pressure, cardiac output and heart rate were measured; systolic stroke volume and peripheral vascular resistance were calculated. 2 (+)-and (-)-Propranolol and pindolol induced a fall of blood pressure but (+)-propranolol was less active. The heart rate was reduced more by (-)-propranolol than by (+)-propranolol or (-)-pindolol. The decrease of systolic stroke volume was greater for (-)-propranolol and pindolol than for (+)-propranolol. Peripheral vascular resistance was reduced to the same level but with different time courses, (-)-propranolol having a longer effect than (+)-propranolol and pindolol. 3 Isoprenaline induced a hypotensive effect, while cardiac output and heart rate increased; the systolic stroke volume remained stable but peripheral vascular resistance was significantly decreased. 4 These results suggest that different central regulatory centres are involved in the control of cardiac function and peripheral vascular tone.

1 Presynaptic fi-adrenoceptor activity was studied in rat isolated atria, previously loaded with[3H]-noradrenaline. The stimulation-induced release of 3H transmitter was measured in the presence of cocaine, and adrenaline was used as a facilitatory #-adrenoceptor agonist. 2 Adrenaline (0.1 and 2 nM) increased, by about 50%, the evoked effiux of tritium. With phenoxybenzamine present, the same activity was shown with 10 nm adrenaline. 3 The 2-selective adrenoceptor blocking drugs: IPS 339 and ICI 118 551 caused a concentrationdependent decrease in the activity of adrenaline. Cardioselective #-blocking drugs: acebutolol, betaxolol, nebivolol and its isomers (R 67 138 and R 67 145) also reduced dose-dependently the agonistic action of adrenaline. The order of potency for nebivolol and its isomers was R 67 138 > nebivolol > R 67 145. The activity of pindolol was not concentration-dependent. The inhibitory effect of acebutolol was also observed in the presence of blockade of a-adrenoceptors.4 The postsynaptic fi-adrenoceptor blocking activity of nebivolol and its isomers was studied in pithed rats. They reduced isoprenaline-induced tachycardia without altering hypotensive responses. The order of potency was: R 67 138 > nebivolol > R 67 145.5 It is concluded that in rat isolated atria, presynaptic 2-and #1-adrenoceptors coexist and that facilitatory fl1-adrenoceptors are stereospecific.

1. Relaxing factors were studied in two perfused preparations of the same vascular area in the rat: resistance mesenteric arterioles and conduit mesenteric artery. 2. In both preparations, an acetylcholine (ACh) infusion inhibited noradrenaline (NA) vasoconstrictor effects but at a ten-times greater concentration in conduit artery than in resistance arterioles. 3. Endothelium destruction with hypotonic Krebs solution did not change basal perfusion pressure, but increased NA responses and suppressed ACh inhibitory effects in arterioles and arteries. Likewise, L-NAME abolished the ACh effect in mesenteric arterioles but only reduced it in mesenteric artery. 4. Basal release of cyclic GMP was significantly greater in mesenteric artery than in resistance arterioles. By contrast, ACh-induced cGMP release was higher in mesenteric arterioles. Endothelium removal did not change basal release of cGMP in mesenteric arterioles but reduced it in mesenteric artery. 5. These results suggest that in basal conditions several relaxing factors are present in higher concentrations in conduit mesenteric artery than in resistance mesenteric arterioles. However, although it releases higher basal amount of cGMP, this vessel has a reduced role in vascular control than do smaller arteries.