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At least 19 recordsLinked to original sources
PubMed1977

High sensitivity of cultured cardiac muscle cells to autonomic agents.

We have established conditions under which cultured embryonic myocardial cells are highly sensitive to the autonomic agents norepinephrine and acetylcholine and have determined that the most important factors affecting this sensitivity involve the application protocol. Using cells 3-5 days in culture, isolated from ventricles of 13-day chick embryos, the ED50 for noerpinephrine was 800 pM and that for acetylcholine was 370 pM. These cells were more than 2 orders of magnitude more sensitive than 13-day embryonic hearts freshly isolated, but not dispersed. Intracellular recording of the membrane actions of norepinephrine and acetylcholine on these cultured cells showed changes in pacemaker slope similar to those seen in freshly isolated hearts. These data demonstrate that preparation of ventricular muscle as isolated cells in culture does not necessarily result in the loss of sensitivity to autonomic agents. On the contrary, the isolated cells show the highest sensitivity to norepinephrine and acetylcholine that has been reported for the myocardium.

Acetylcholine↗
PubMed1976

Effect of experimental diabetes, food deprivation and genetic obesity on the sensitivity of pithed rats to autonomic agents.

1 The sensitivities of alloxan and streptozotocin diabetic and hereditary obese pithed rats to acetylcholine, isoprenaline and noradrenaline were compared to those of controls. 2 Blood pressure and heart rate recordings made before dosing was started showed the streptozotocin-treated animals to have a significantly reduced heart rate and increased pulse pressure as compared with controls. 3 Both diabetic groups were found to have reduced sensitivities to the pressor effect of noradrenaline, the depressor effect of acetylcholine, the positive chronotropic and inotropic effect of isoprenaline and the reduction in diastolic pressure induced by isoprenaline. The reduction in sensitivity was generally much greater in the streptozotocin diabetic animals. 4 The genetically obese rats were found to have similar sensitivities to all three agents as did their non-obese litter mates. 5 When either diabetic group was deprived of food for 24 h preceding the tests the sensitivities were found to be raised significantly towards normal in almost all cases. 6 The results are contrasted with previous in vitro results and possible causative metabolic factors discussed. It is suggested that sensitivity changes are unevenly distributed within the cardiovascular system.

Acetylcholine↗
PubMed1978

Effect of autonomic agents on the amount of androgen-dependent granules in convoluted tubular cells of the mouse submandibular gland.

The convoluted tubular cells of the male mouse submandibular gland contain many serous-like granules in their apical cytoplasm. The autonomic regulation of the secretory process of the contents of these granules was studied by the following two methods: (1) immunochemical method using an antiserum specific to the granular components; and (2) histometric observations using light and electron microscopes. The results obtained by these two methods were well in agreement. When male mice were administered either phenylephrine or norepinephrine, the amount of granules in the glands significantly decreased. These two adrenergic stimulators were very effective, whereas synephrine was less effective. When mice were injected with a beta-adrenergic agent(isoproterenol) or a parasympathomimetic agent (pilocarpine), the amount of granules in the glands did not change. The alpha-adrenergic blockers phenoxybenzamine and phentolamine almost completely neutralized the effect of alpha-adrenergic agents on the glands, whereas another alpha-blocker (ergotamine) was less effective. These facts suggest that the secretion of the granular components is mediated by way of alpha-adrenergic receptor sites in the glands.

Adrenergic alpha-Agonists↗
PubMed1979

Reactivity of isolated canine bronchus and pulmonary blood vessels to autonomic, autacoid agents and antigen.

Adult dogs were sensitized to horse plasma. Reactivity of isolated bronchus and pulmonary blood vessels to antigen and some selected autonomic and autacoid agents were studied. Pulmonary veins contracted to bradykinin, 5-HT, PGF2alpha, PGE2, histamine, carbachol and antigen (Schultz-Dale reaction). Pulmonary arterial strips contracted to 5-HT and histamine, but only weakly to horse plasma. Bronchial strips contracted to carbachol, 5-HT, histamine and horse plasma, relaxed to isoprenaline, PGE1 and PGE2. Subsequent antigen challenge produced 'desensitization'. Allowing the tissues to 'rest' for 1 and 2 h resulted in partial 'recovery' of the anaphylactic response. This investigation suggests that the contractions of sensitized pulmonary vein and bronchus to specific antigen may contribute to the patho-physiology of pulmonary hypersensitivity in dogs.

Anaphylaxis↗
PubMed1978

Effect of autonomic blocking agents on chronotropic actions of 1-alpha-acetylmethadol.

The objective of this investigation was to determine whether or not autonomic receptors are involved in the chronotropic responses to 1-alpha-acetylmethadol (LAAM) and congeners (1-alpha-acetylnormethadol, norLAAM; 1-alpha-acetyldinormethadol, dinorLAAM). The effects of atropine were studied in vitro using isolated guinea-pig right atria and in vivo in anesthetized dogs. The effect of d,l-propranolol, a beta-adrenergic receptor blocking agent was studied in vitro only. Atropine attenuated, but did not block completely, the negative chronotropic responses to the narcotic agonists. Propranolol blocked completely the positive chronotropic response to norLAAM and appeared to increase the negative chronotropic response to dinorLAAM. It is concluded that: 1) muscarinic cholinergic receptors play a role in the negative chronotropic response; 2) the positive chronotropic response to norLAAM involves activation of beta-adrenergic receptors.

Animals↗
PubMed1975

[Antiviral chemotherapeutic agents. XVIII. Adamantane derivatives of amphetamine. Their potential interest as autonomic and antiparkinson agents].

Adamantane isologs of amphetamine, methamphetamine and pheniprazine and several derivatives were synthesized in order to study the influence of their more pronounced lipophilic characteristics on their biological properties. A preliminary examination of their toxicity, antiviral, CNS stimulant and antiparkinson activity is described. The adamantyl amphetamine, which proved active, will be further studied.

Adamantane↗
PubMed1979

Mechanisms of late decelerations in the fetal heart rate. A study with autonomic blocking agents in fetal lambs.

Fetal heart rate decelerations resembling the late deceleration FHR pattern were produced in fetal sheep by periodic occlusion of the maternal common hypogastric artery for 30-60 sec. Transient fetal hypertension also occurred during the occlusions. Alpha-adrenergic blockade with phentolamine eliminated or markedly reduced the hypertensive response. FHR decelerations still occurred intermittently with some occlusions; however, their character was greatly altered. After parasympathetic blockade with atropine, the decelerations were replaced by periodic FHR accelerations during the occlusions. These accelerations were, in turn, eliminated by the beta-adrenergic blocking agent, propranolol. In the presence of combined parasympathetic, alpha- and beta-adrenergic blockade, the FHR remained essentially constant during the hypogastric artery occlusions in non-acidemic fetuses. FHR decelerations persisted after parasympathetic or total autonomic blockade when the fetuses were significantly hypoxic, as judged by depressed arterial blood pH and base excess values. Beat-to-beat variability of the baseline FHR persisted in the face of severe hypoxia and acidosis. These observations demonstrate that reflex mechanisms are involved importantly in the genesis of late deceleration FHR patterns in the acutely hypoxemic fetus, but that direct depression of myocardial rhythmicity becomes a factor as hypoxic acidosis develops.

Acetylcholine↗
PubMed1976

Analysis of cardiac chronotropic responses to some autonomic blocking agents in conscious trained dogs.

The changes of heart rate in response to i.v. administration of methylatropine (0.5 mg/kg) and/or propranolol (2 mg/Kg) or practolol (2.5 mg/Kg) were studied in conscious trained dogs. Cholinergic blockade alone or combined blockade of sympathetic and parasympathetic effector systems resulted in cardiac acceleration. Conversely, beta-adrenoceptor antagonism with either propranolol or practolol reduced heart rate. The data were analysed by means of a new method, whereby the heart (HRN) of the dog is considered to be the product of the intrinsic heart rate (HR0) and 3 further factors: HRN-HR0 times S times V times W (Multiplicative model). 2 of these factors represent the tonic sympathetic (S) and parasympathetic (V) influences, whereas the third (W) represents the sympathetic-parasympathetic interaction. This type of analysis reveals that W was approximately 1, i.e., the sympathetic-parasympathetic interaction did not play any significant role in determining the heart rate of conscious resting dogs (HRN = HRO-S-V-W = HRO-S-V). The change of heart rate due to the action of parasympathetic system (-53% of the intrinsic heart rate) was more important than the change caused by the action of the sympathetic system (26% of the intrinsic heart rate).

Animals↗
PubMedDate not supplied

The beta-adrenergic blocking agents and the treatment of glaucoma.

The autonomic nervous system is divided into the parasympathetic and sympathetic systems, with three types of adrenergic receptors: alpha (smooth muscle contraction), beta1 (cardiac acceleration and fatty acid mobilization) and beta2 (smooth muscle relaxation). Substances affecting the function of the adrenergic system are the agonists or stimulators, which mimic the effects of endogenous norepinephrine or epinephrine, and antagonists or blockers, which block the receptors and prevent stimulation by the agonists. Autonomic stimulation in the eye mediates various changes which apparently affect outflow facility and rate of formation of aqueous humor. Alteration of either or both of these factors by autonomic agonists or antagonists may have a direct or an indirect effect on intraocular pressure. Beta-adrenergic blocking substances have been used to treat a variety of diseases. Some of the effects of these drugs are attributable to properties other than beta blockade, such as intrinsic sympathomimetic activity and local anaesthetic activity. Side effects of this class of drugs require caution in cases of congestive heart failure and in asthmatics. Autonomic agents used in the treatment of ocular hypertension and glaucoma include pilocarpine, a chilinergic agonist, epinephrine, an adrenergic agonist, and various beta adrenergic blockers or antagonists including propranolol, atenolol and timolol. The physico-chemical properties and pharmacokinetics of timolol are reviewed. Data showing a significant reduction in intraocular pressure as a result of ocular instillation of timolol are presented. Reduction of the rate of aqueous formation appears to be the mechanism of action. A low incidence of non-serious side effects is reported.

Adrenergic beta-Antagonists↗
PubMed1979

Oxybutynin influence on autonomic measures in dogs.

In the conscious dog, the most apparent oxybutynin effect was a dose-related tachycardia. Associated with this heart rate increase were a very slight, sometimes significant, elevation in diastolic pressure and an insignificant increase in systolic pressure. Under pentobarbital anesthesia, the systolic/diastolic arterial pressure oxybutynin responses were reversed and showed a dose-related systolic and diastolic hypotension. However, the tachycardic response to oxybutynin still appeared. The arterial pressure and heart rate responses produced by the autonomic agents were altered by the oxybutynin treatment in a pattern indicative of an anticholinergic mechanism of action. Differences in many response profiles were observed with either conscious or anesthetized dogs, but the statistically significant inhibition of the acetylcholine-induced systolic and diastolic arterial pressure and bradycardic responses were constant in both conditions. Oxybutynin is an anticholinergic agent with mild to moderate cardiovascular activity.

Anesthesia↗
PubMed2026

Artificial intelligence agents and agentic artificial intelligence applied to precision medicine.

Precision medicine seeks to individualise care by integrating multimodal biomedical data, yet most deployed clinical artificial intelligence (AI) remains assistive, providing predictions without managing workflows or adapting autonomously. Agentic AI, built on large language models (LLMs), has emerged as a paradigm characterised by autonomy, goal-directed reasoning, memory, planning and tool use. This review synthesises evidence on agentic AI and LLMs applied to precision medicine, encompassing drug discovery, genomics, oncology, rare disease diagnostics and clinical pharmacology. This review also examines architectural components, recent validation milestones and emerging challenges, including hallucination, sociodemographic bias and evolving regulatory frameworks across the FDA, the EU AI Act and the WHO.

agentic AI↗
PubMed1976

Pharmacodynamic actions of (S)-2-[4,5-dihydro-5-propyl-2-(3H)-furylidene]-1,3-cyclopentanedione (oudenone).

The pharmacodynamic actions of (S)-2-[4,5-dihydro-5-propyl-2(3H)-furylidene]-1,3-cyclopentanedione (oudenone) were studied in both anesthetized animals and isolated organs. Oudenone (10--40 mg/kg i.v.) induced an initial rise in blood pressure followed by a prolonged hypotension in the anesthetized rats. In unanesthetized spontaneously hypertensive rats (SHR), oudenone (5--200 mg/kg p.o.) caused a dose-related decrease in the systolic blood pressure. The initial pressor effect was diminished by pretreatments with phentolamine, guanethidine, hexamethonium and was abolished in the pithed rats. In addition, intracisternal administrations of oudenone (100--600 mug/kg) showed a marked increase in blood pressure in the anesthetized rats, suggesting that the pressor effect may be due to centrally mediated actions. Oudenone, given intra-arterially into the femoral artery (400--800 mug/kg), caused a long-lasting vasodilation in anesthetized dogs. At a relatively high dose (40 mg/kg i.v.), oudenone antagonized all pressor responses to autonomic agents and central vagus nerve stimulation in anesthetized rats and dogs, however, oudenone showed no anti-cholinergic,-histaminergic, beta-adrenergic and adrenergic neuron blocking properties.

Adrenalectomy↗
PubMed1977

Motor innervation of the smooth muscle of the rat seminal vesicle.

Frequency-related isovolumetric contractions of the rat seminal vesicle elicited with transmural electrical stimulation were blocked by tetrodotoxin but unaffected by hexamethonium. The postganglionic motor innervation of the rat seminal vesicle is purely excitatory and contains both an adrenergic and a cholinergic component which are excited simultaneously during transmural stimulation. Contractions elicited by adrenergic nerve stimulation were mediated by norepinephrine acting via alpha adrenoceptors, i.e., 1) responses of untreated vesicles to transmural stimulation and to exogenous norepinephrine were antagonized by phentolamine and potentiated by cocaine, 2) pretreatment of animals with reserpine or 6-hydroxydopamine produced a marked depletion of tissue norepinephrine concentration and reduced the responses to transmural stimulation to a level which resembled that of untreated organs in the presence of phentolamine, 3) the residual responses of vesicles from pretreated rats were not modified by phentolamine or cocaine, and 4) responses to tyramine in untreated organs were antagonized by phentolamine but not by cocaine and were observed in organs from reserpine-pretreated rats only after repletion with exogenous norepinephrine. Responses elicited by cholinergic nerve stimulation were mediated by acetylcholine through muscarinic receptors, i.e., 1) responses of untreated vesicles to transmural stimulation and to exogenous acetylcholine were antagonized by atropine, 2) the residual responses to transmural stimulation of vesicles from animals pretreated with reserpine of 6-hydroxydopamine were nearly abolished by atropine and 3) physostigmine potentiated and prolonged the responses of organs from untreated and reserpine-pretreatd animals to transmural stimulation; these effects of physostigmine were abolished by atropine.

Animals↗