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5-HT induced an increase in blood pressure in the pithed rat which was antagonized by LY 53857 a selective 5-HT 2 receptor antagonist. It was not antagonized by spiroxatrine, MDL 72222, idazoxan or AR-C 239, respectively 5-HT 1 -like and 5-HT 3 receptor antagonists, α 2 - and α 1 -adrenocepto antagonists. 5-MeODMT also induced an increase in blood pressure which was antagonized by LY 53857 but not by the other 5-HT receptor antagonists and α-adrenoceptor antagonists used, suggesting a 5-HT 2 component in the pressor effect of 5-MeODMT. The maximal effect of 5-MeODMT was less marked than that of 5-HT. 8-OH-DPAT, RU 24969 and TFMPP were far less effective than 5-HT and 5-MeODMT to increase blood pressure. In contrast, 5-CT induced a vasodepressor effect. It is therefore suggested that the vasoconstriction induced by 5-HT and 5-MeODMT in pithed rats could be due mainly to the selective stimulation of postjunctional 5-HT 2 receptors because selective α 2 - and α 2 -adrenoceptor antagonists were ineffective against the vasoconstrictor effects of 5-HT and 5-MeODMT. The relative lack of effect of 8-OH-DPAT, RU 24969 and TFMPP to increase blood pressure suggested that postjunctional 5-HT 1 -like receptors play only a minor role — if any — 5-HT induced vasoconstriction in the pithed rat.

Fentanyl (10 and 30 mug/kg), a narcotic analgesic, induced in cats a decrease in blood pressure and heart rate and reduced spontaneous splanchnic nerve activity. Fentanyl reduced the pressor response to medullary stimulation, but did not change the pressor response to hypothalamic or cervical spinal cord stimulation. Fentanyl reduced the potential evoked in the splanchnic nerve by stimulation at low frequency of a pressor area of the medulla oblongata. The potentials evoked in the splanchnic nerve by hypothalamic or cervical spinal cord stimulation were only slightly changed. Nalorphine (0.5 mg/kg) or naloxone (30 mug/kg) induced a recovery in blood pressure, heart rate and spontaneous splanchnic discharges which had been reduced by fentanyl, but nalorphine or naloxone did not restore pressor response to medullary stimulation or potentials evoked in the splanchnic nerve by medullary stimulation, which had been decreased by fentanyl.

Injection of a small dose of yohimbine, an alpha 2-adrenoceptor blocking agent (0.1 mg X kg-1 i.v.) increased systolic blood pressure, heart rate and cardiac performance in anaesthetized dogs. A larger dose of this drug (1 mg X kg-1 i.v.) influenced the cardiovascular system in an opposite way. The tachycardiac effect of yohimbine was also observed when the drug was administered either into the vertebral artery or the cisterna magna of chloralosed dogs. The increase in heart rate was found to be due to an increase in sympathetic tone and to a decrease in vagal tone. Some data reported here suggest that yohimbine could impair central cardiovascular regulation by acting on the baroreceptor reflex pathway. Indeed, intracisternal administration of yohimbine at small doses (1) reduced the tachycardiac and pressor responses to carotid occlusion, (2) reduced the bradycardia produced by intravenous noradrenaline. It is also suggested from the results of this investigation that yohimbine decreases the vagal part of the bradycardia resulting from the stimulation of the aortic baroreceptors but not those resulting from the stimulation of carotid sinus baroreceptors. Intracisternal administration of yohimbine also produced a significant inhibition of the Bezold-Jarish reflex induced by intravenous veratridine.

The influence of some α- and β-adrenoceptor blocking agents on the sleep induced by clonidine (1.2 mg/kg, i.m.) in chickens has been investigated. Yohimbine (0.1 – 2 mg/kg) antagonized very effectively the effect of clonidine. 883F (20 mg/kg), dibozane (20 mg/kg), ethomoxane (20 mg/kg), azapetine (20 mg/kg), mosixylite (20 mg/kg) lacked effect. Pindolol (1 mg/kg), Ko 1366 (1 mg/kg) and S.2395 (1 mg/kg), three potent β-adrenoceptor blocking compounds, as well as alprenolol, sotalol, practolol and dichloroisoproterenol were without effect. In mice, yohimbine antagonized very effectively the prolongation of chloral-induced sleep by clonidine; 883F was effective at high dosage but the other α-adrenoceptor blocking agents were ineffective. These results support the hypothesis that sedation induced by clonidine is mediated by the activation of α-adrenoceptors different from the peripheral adrenoceptors.

Dose-response curves for nine α-sympathomimetic drugs were determined in pithed rats. The order of potency was: norepinephrine 1, phenylephrine 0.1, oxymetazoline 0.1, clonidine 0.029, LD 2855 0.028, naphazoline 0.087, tramazoline 0.030, tetryzoline 0.01, Bayer 1470 0.0003. Pretreatment with reserpine (10 mg/kg 24 hr before) did not change the dose-response curves; phentolamine (2 mg/kg) shifted the dose-response curve to the right but did dose-response curve to the right and reduced the maximal response suggesting non-competetive antagonism. Cocaine (5 mg/kg) and imipramine (2 mg/kg) reduced the hypertension produced by clonidine but increased slightly hypertension following naphazoline. Clonidine (3–30 μg/kg) induced biphasic changes in blood pressure — a rise followed by a long decrease, bradycardia, decrease in aortic blood flow, femoral and coronary blood flows. Naphazoline (5 to 45 μ/kg) induced a rise in blood pressure, a fall in aortic blood flow, a bradycardia, a pulmonary hypertension, a decrease in femoral and coronary blood flows. Total, pulmonary, coronary and femoral resistances were elevated. Performances of the left ventricle were reduced. The mechanisms of these changes were discussed.

2(2, 6-dichlorophenylamino)-2 imidazoline hydrochloride (S.T. 155) induced in dogs a long lasting hypotension following a brief increase in blood pressure. At low doses, S.T. 155 decreased strikingly the discharges in the splanchnic and inferior cardiac nerves; this was also obtained in debuffered animals. This reduced sympathetic tone appeared to be the cause of the fall in blood pressure.

2-(2,6-Dimethylphenylamino)-4-H-5,6-dihydro-1,3-thiazin (Bayer 1470) produced short-lasting hypertension followed by long-lasting hypotension and a reduced heart rate in dogs, cats, rabbits and rats. In pithed rats, Bayer 1470 produced only hypertension and reduced pressor responses to stimulation of the entire sympathetic system at low intensity or frequency but did not change the maximal effect. In dogs and cats, Bayer 1470 markedly reduced action potentials recorded from the splanchnic nerve and the inferior cardiac nerve. The effect was centrally mediated for it was encountered in debuffered dogs. In cats and rabbits, the electrical activity in the cervial sympathetic trunk was reduced but less so than in other sympathetic nerves. Bayer 1470 reduced pressor responses to carotid occlusion although an increased splanchnic discharge could still be elicited. In rats, Bayer 1470 reduced the frequency and amplitude of splanchnic discharges which were in phase with respiration but in contrast to dogs and cats a clearcut correlation between central inhibition of the sympathetic tone and the hypotension was not obtained. In addition Bayer 1470 reduced the pressor responses and splanchnic discharges caused by hypothalamic stimulation. Intracisternal and intraventricular injections of Bayer 1470 produced hypotension and a decreased sympathetic discharge. In conclusion, Bayer 1470 reduced sympathetic tone both by a central and peripheral action; the central action appeared to predominate. Its mechanism of action appears to be closely related to that of St 155.

IT has been shown1,2 that the effects of sympathomimetic amines, called indirect (tyramine, phenylethylamine, phenylethanolamine, ephedrine, amphetamine), are abolished by pretreatment with reserpine. However, immediately after an injection of reserpine, the effects of indirect sympathomimetic amines are potentiated2,3. On the other hand, it has been reported that bretylium enhances the effects of tyramine4.

Mitochondrial DNA isolated from cysts of Artemia salina (brine shrimp) was found to have a closed-circular structure 5.1 μm long and a buoyant density of 1.697 g/cm3. Escherichia coli RNA polymerase can transcribe this DNA. RNA synthesis is greatly stimulated by the σ subunit and is influenced by the presence of KCl. After formation of an initial complex between the enzyme and the mitochondrial DNA only a limited synthesis of RNA took place in the presence of rifampicin. The products obtained with holo enzyme and core enzyme in the presence of excess nucleoside triphosphates have a mean molecular weight of 1.5 × 106 and greater than 3 × 106 respectively, as determined by acrylamide-agarose gel electrophoresis. Addition of the termination factor ϱ to the reaction mixture reduced the molecular weight of the products to 1.0 × 106 at a KCl concentration of 0.05 M but not at 0.1 M KCl. Under limiting UTP concentrations, a few discrete RNA bands of shorter size (about 8 × 105, 105 and 3 × 104 mol. wt) are synthesized. Addition of ϱ factor to the reaction mixture caused the disappearance of the higher-molecular-weight band (8 × 105) while the other RNA bands remained. Little self-annealing was observed upon heating the [3H]RNA synthesized in vitro at 70 °C. On the other hand, when the [3H]RNA was heated in the presence of unlabeled mitochondrial rRNA, about 54% of the labeled product was resistant to degradation by a mixture of T1 and pancreatic RNase. In hybridization-competition experiments, annealing of the [3H]RNA synthesized in vitro was reduced by 65% upon addition of unlabeled mitochondrial rRNA. RNA-RNA annealing is thought to be the main cause for this competition reaction since similar results were obtained by simultaneous or step-wise hybridization procedures. It is concluded that transcription in vitro of closed circular-mitochondrial DNA from Artemia by E. coli RNA polymerase proceeds mainly on the anti-rRNA strand.

IT has been reported by Atlas, Hanski and Levitzki that muscle cells have an unusually high number of β adrenoreceptors, 80,000 per cell1 However, we consider the pharmacological characterisation of these receptors as specific β adrenoreceptors unsatisfactory. We report here that the number of specific β adrenoreceptors in a similar but not identical muscle cell line of the same origin is 8,000 rather than their stated figure of 80,000, and is therefore comparable to that found on C6 glioma cells.

We tested the hypothesis that atrial natriuretic peptide (ANP) has a direct negative inotropic effect on the cultured chick embryo ventricular cell, an experimental system devoid of endogenous neurotransmitters. At 10(-8) and 2.5 x 10(-7) mol/l ANP [rat ANP-(1-23)] significantly and reversibly decreased contractility in spontaneously beating cells. The positive inotropic effect of angiotensin II (2.5 X 10(-7) mol/l) on spontaneously beating cells was fully antagonized by ANP (2.5 X 10(-7) mol/l) and the amplitude of contraction decreased below control levels. In contrast (1) the increase in contractility in response to extracellular calcium was significantly less altered by ANP and (2) the time-course of the positive inotropic effect of the calcium-channel agonist Bay-K-8644 (5 x 10(9) mol/l) or of the beta-adrenergic agonist isoproterenol (10(-6) mol/l) was unchanged by ANP. These results indicate that ANP-(1-23) has a direct negative inotropic effect on cultured chick heart cells and may affect intracellular messengers involved in the cardiac effects of angiotensin II.

The blood pressure is not disturbed by a local injection of norepinephrine into the hypothalamus, but the excitability of vasopressor centres is affected. Often, the excitability of these centres is decreased; sometimes, it is increased, and, more rarely, it is first potentiated and then inhibited. Epinephrine has the same action, but dopamine is less potent; isoprenaline produces both facilitation and inhibition of these centres, but the facilitating effect is more frequent than with norepinephrine.