Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Autonomic Pathways”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,297 records · Page 72Linked to original sources
PubMed1981

The organization of lumbar preganglionic neurons.

The organization of pre- and postganglionic neurons supplying blood vessels of the skin (vasoconstrictor neurons) and of the skeletal muscle (vasoconstrictor neurons), sweat glands (sudomotor neurons) and erector pilimuscles (pilomotor neurons) of the cat's hind limb and tail is discussed. Each sympathetic subsystem has its own, though as yet unknown, central organization which is reflected in the reaction patterns typically seen. The conduction velocities of the pre- and postganglionic axons of each subsystem have their unique distributions. Postganglionic vasoconstrictor neurons supplying skeletal muscle and skin are influenced via cholinergic muscarinic and non-cholinergic synaptic mechanisms from thin, probably unmyelinated, preganglionic axons; postganglionic sudomotor and pilomotor neurons most likely do not receive this synaptic input. A high proportion of preganglionic neurons projecting with their axons onto postganglionic neurons which supply skin and skeletal muscle are silent and do not exhibit reflex activity. Some of these neurons synapse with postganglionic pilomotor, vasodilatator and sudomotor neurons; part of them may also synapse with vasoconstrictor neurons. However, the high proportion of preganglionic neurons without reflex and resting activity which cannot be classified on the basis of functional properties presents a considerable problem in the analysis of the central organization of the sympathetic nervous system. It is concluded that the 4 types of pre- and postganglionic neurons mentioned constitute 4 largely separate channels which transmit information from the spinal cord to the respective target organs.

Afferent Pathways↗
PubMed1982

Changes in unmyelinated fibers including sympathetic postganglionic fibers of a skin nerve after peripheral neuroma formation.

Conduction velocities of unmyelinated fibers and proportions of postganglionic fibers which can be activated from the lumbar sympathetic trunk were determined for the superficial peroneal nerve of the cat's hindlimb. The nerve was either left intact (4 control experiments) or cut and ligated peripherally 6-245 days before the experiments so that neuromata developed (15 experiments). Additionally, 3 control experiments were performed on the sural nerve. Our findings are that about 20-30% of all unmyelinated fibers in intact skin nerves are postganglionic sympathetic fibers. This percentage of postganglionic axons, which can be activated from the preganglionic side, decreases to 0-7% 100 days or more after the nerve section. In intact skin nerves the conduction velocity of the afferent unmyelinated fibers is greater (mean +/- 1 S.D.: 0.88 +/- 0.17 m/s) than that of postganglionic axons (0.69 +/- 0.14 m/s). The conduction velocities in both types of axons decrease by 25-30% in nerves with peripheral neuroma. This occurs largely during the first 15 days following the nerve section described.

Adrenergic Fibers↗
PubMed1982

Parasympathetic preganglionic neurons in the sacral spinal cord.

Two types of preganglionic neurons have been identified in the sacral parasympathetic nucleus (SPN) of the cat. These neurons could be differentiated by various characteristics including axonal conduction velocities, morphology, location in the nucleus, organ of innervation and central reflex mechanisms controlling their activity. Neurons having myelinated axons (B-PGNs) with conduction velocities between 3.3 and 13 m/s were located in the lateral band of the SPN and innervated the urinary bladder. Neurons with unmyelinated axons (C-PGNs) with conduction velocities of 0.5-1.4 m/s were located in the dorsal band of the nucleus and innervated the large intestine. B-PGNs were excited by distention of the bladder and inhibited by distension or mechanical stimulation of the intestine, whereas C-PGNs exhibited the opposite responses to these stimuli. C-PGNs often exhibited a low level of spontaneous discharge in absence of stimulation but exhibited marked firing (3.5-10 spikes/s) during a defecation reflex elicited by mechanical stimulation of the rectum-anal canal. The excitatory responses were elicited by C-fiber afferents via a spinal reflex pathway. B-PGNs were inactive when intravesical pressure was below the threshold for inducing micturition (5 cm H2O) but raising the pressure above the threshold induced firing consisting of repetitive bursts of action potentials occurring at relatively high frequencies (15-60 spikes/s). These bursts coincided with rhythmic bladder contractions. The frequency of bladder contractions and associated bursts of PGN-firing and the mean PGN-firing rate (2-8 spikes/s) increased as intravesical pressure was increased in steps between 5 and 30 cm H2O. However, as indicated by interspike interval histograms, the frequency of firing within a burst of action potentials was unchanged. It is concluded that the micturition reflex pathway is organized as a simple on-off switching circuit and that B-PGNs receive a maximal synaptic input when intravesical pressure exceeds the micturition threshold. This circuit was triggered by vesical A delta afferents via a spinobulbospinal pathway. Transection of the spinal cord interrupted the reflex pathway and blocked micturition. However, in chronic spinal animals a spinal reflex mechanisms emerged which contributed to the recovery of bladder function. This mechanism, which was weak or non-existent in animals with an intact neuraxis, exhibited a number of important differences from the normal micturition reflex, most notably being activated by a C-fiber afferent rather than a A delta afferent limb. The mechanism underlying the emergence of C-fiber evoked bladder reflexes in spinal animals is uncertain.

Action Potentials↗
PubMedDate not supplied

Somato-vesical reflexes in chronic spinal cats.

The effects of afferent volleys in hindlimb cutaneous and muscle nerves on vesical tone and contractility and on the discharges in pelvic nerves to the bladder were measured in anesthetized CNS-intact and 2-19 months chronic spinal cats. In chronic spinal cats volleys in group III and IV fibers increased the tone of the quiet, empty bladder (excitatory somato-vesical reflex). The same volleys inhibited the slow, large, rhythmic micturition contractions of the expanded bladder (inhibitory somato-vesical reflex). In CNS intact cats single or short tetanic volleys induced a reflex discharge in pelvic vesical nerve branches with 3 distinct components. These reflexes could be observed during micturition contractions, not markedly between the contractions or when the bladder was empty and quiet. The latencies of the 3 components were 90, 320 and 770 ms, respectively. The two early components (AI- and A2-reflex) were evoked by volleys in group II and III hindlimb afferents. The late component (C-reflex) was induced by group IV volleys. In chronic spinal cats a group II and III-induced A-reflex (latency 90 ms) and a group IV-induced C-reflex (latency 340 ms) were observed. The central pathways and the physiological significance of the various somato-vesical reflexes are discussed.

Afferent Pathways↗
PubMed1985

The components of the hypogastric nerve in male and female guinea pigs.

A quantitative study has been made of the neural components of the hypogastric nerves of male and female guinea pigs using retrograde transport of horseradish peroxidase (HRP) to identify the population of neurones projecting in the nerve trunk, and electronmicroscopic analysis of the myelinated and unmyelinated axons present. Application of HRP to the transected axons of the hypogastric nerve labelled the cell bodies of sensory neurones in lumbar and sacral dorsal root ganglia, preganglionic neurones in the lumbar and sacral spinal cord, and postganglionic neurones in the inferior mesenteric ganglion and in the lumbar paravertebral chain; some ganglion cells of the pelvic plexus were also labelled. The number and distribution of each type of neurone with axons in the hypogastric nerve differed between the sexes: in particular, about twice as many preganglionic axons were present in the male as in the female.

Afferent Pathways↗
PubMed1985

Reflex patterns in postganglionic vasoconstrictor neurons following chronic nerve lesions.

Lesions of limb nerves in man may be associated with a variety of painful disorders with trophic changes described by the generic term 'reflex sympathetic dystrophy'. Our hypothesis is that pain and trophic changes are produced by an abnormal discharge pattern in postganglionic neurons supplying the limb (see refs. 3,24). In relation to this hypothesis, reflex patterns in postganglionic vasoconstrictor neurons supplying the skin (CVC) and the skeletal muscle (MVC) of the cat hindlimb were investigated at various times after a peripheral nerve lesion had been produced. These reflex patterns were compared with those in animals without nerve lesions (control preparations). The following lesions were made: cutting and ligating the superficial peroneal nerve (skin nerve) with subsequent neuroma formation, suturing the central stump of the superficial peroneal nerve to the peripheral stumps of muscle branches of the deep peroneal nerve, suturing the central stumps of muscle branches of the deep peroneal nerve to the peripheral stump of the superficial peroneal nerve, cutting and resuturing the superficial peroneal nerve, deafferentation of the whole hindlimb. The responses of vasoconstrictor neurons to stimulation of arterial chemoreceptors, arterial baroreceptors (cardiac rhythmicity of postganglionic activity) and cutaneous nociceptors were tested. In the animals with nerve lesions, the following groups of postganglionic vasoconstrictor neurons were analyzed: neurons projecting to the lesioned nerve, neurons projecting to hairy skin through an intact skin nerve (sural nerve) and neurons projecting to skeletal muscle through intact muscle nerves. In control preparations without nerve lesions, MVC neurons were excited by stimulation of arterial chemoreceptors and cutaneous nociceptors and inhibited by stimulation of arterial baroreceptors. Most CVC neurons were inhibited by stimulation of chemoreceptors and nociceptors and weakly inhibited by stimulation of baroreceptors. In animals with nerve lesions a and b, many CVC neurons in the lesioned nerves, as well as in the non-lesioned cutaneous nerve nearby, behaved in the same manner as MVC neurons. With respect to the control, this difference proved to be statistically significant. In preparations with lesions a, b and c, MVC neurons did not change their reflex patterns. After nerve lesions d and e, no major changes of reflex patterns were observed in CVC and MVC neurons. The inhibitory influence of arterial baroreceptors on CVC activity decreased in deafferented preparations (lesion e).(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1992

Pharmacological prospects for alpha 2-adrenoceptor antagonist therapy.

The discovery of various alpha 2-adrenoceptor subtypes in numerous tissues and studies of alpha 2-adrenoceptor-mediated mechanisms has generated considerable interest in their physiological functions. It has also increased possibilities for the design of new pharmacological tools and for the study of the pharmacological impact of new drugs. Alpha 2-adrenoceptors are located pre- and postsynaptically both in the central noradrenergic pathways and on the autonomic nerve endings. It is difficult to dissociate alpha 2-adrenoceptor-mediated autoregulation, involving presynaptic receptors, from actions dependent on post- and extrajunctional alpha 2-adrenoceptor activation. A lot of alpha 2-adrenoceptors are subject to permanent tonic activation by the sympathetic nervous system. Max Lafontan and colleagues review the major actions of alpha 2-adrenoceptors and consider the sites of impact of alpha 2-antagonists that could initiate further research for putative applications of these drugs. Many of the possible targets for alpha 2-adrenoceptor antagonists have not yet been explored clinically.

Adrenergic alpha-Antagonists↗
PubMed1988

Anatomical localization of afferent and postganglionic sympathetic neurons innervating the rat ovary.

The fluorescent retrograde tracer, True blue, was applied directly to either the superior ovarian nerve (SON) or the ovarian plexus nerve (OPN) in the rat. Afferent perikarya were located in lower thoracic-upper lumbar dorsal root ganglia and projected to the ovary via both nerve routes. Postganglionic sympathetic efferent perikarya were located in both prevertebral and thoracolumbar paravertebral ganglia and also utilized both the SON and OPN to reach the ovary. The significance of the dual origin of postganglionic sympathetic neurons innervating the rat ovary is not known.

Afferent Pathways↗
PubMed1982

Substance P as an excitatory transmitter of primary afferent neurons in guinea-pig sympathetic ganglia.

Electrophysiological and neurochemical experiments were carried out to examine a possible transmitter role substance P in the prevertebral ganglia of the guinea-pig. When potentials were recorded intracellularly from neurons of the isolated ganglia, stimulation of the pre- or postganglionic nerves elicited a non-cholinergic slow excitatory postsynaptic potential (EPSP). This synaptic potential was compared with the effects of substance P. Brief application of substance P caused a depolarization of the ganglion cells with a similar time course to that of the non-cholinergic slow EPSP. Changes in membrane resistance during the substance P-induced depolarization resembled those associated with the non-cholinergic slow EPSP. During the substance P-induced depolarization the non-cholinergic slow EPSP was markedly depressed. Attempts were made to determine the origin of the fibers eliciting the non-cholinergic slow EPSP. In the inferior mesenteric ganglia isolated together with preganglionic nerves that retained intact connections with spinal nerve roots, dorsal root stimulation evoked a non-cholinergic slow EPSP but not a cholinergic fast EPSP in the ganglion cells, whereas ventral root stimulation caused only cholinergic fast EPSPs. Following the prolonged treatment with capsaicin, the non-cholinergic slow EPSP was greatly depressed or abolished. Radioimmunoassay revealed that after ligation or section of pre- or postganglionic nerves an accumulation of substance P occurred in the proximal stumps of the interrupted nerves. Stimulation with high potassium medium evoked a release of immunoreactive substance P from the prevertebral ganglia and the release was calcium-dependent. The present findings suggests that axon collaterals of certain visceral primary efferents form synapses with principal cells in the prevertebral ganglia and release substance P as a transmitter for the non-cholinergic slow EPSP.

Adrenergic Fibers↗
PubMed1982

The organization of afferent projections to the midbrain periaqueductal gray of the rat.

The retrograde transport technique was utilized in the present study to investigate the afferent projections to the periaqueductal gray of the rat. Iontophoretic injections of horseradish peroxidase were made into the periaqueductal gray of 22 experimental animals and into regions adjacent to the periaqueductal gray in 6 control animal. Utilization of the retrograde transport method permitted a quantitative analysis of the afferent projections not only to the entire periaqueductal gray, but also to each of its four intrinsic subdivisions. The largest cortical input to this midbrain region arises from areas 24 and 32 in the medial prefrontal cortex. The basal forebrain provides a significant input to the periaqueductal gray and this arises predominantly from the ipsilateral lateral and medial preoptic areas and from the horizontal limb of the diagonal band of Broca. The hypothalamus was found to provide the largest descending input to the central gray. Numerous labeled cells occurred in the ventromedial hypothalamic nucleus, the lateral hypothalamic area, the posterior hypothalamic area, the anterior hypothalamic area, the perifornical nucleus and the area of the tuber cinereum. The largest mesencephalic input to the periaqueductal gray arises from the nucleus cuneiformis and the substantia nigra. The periaqueductal gray was found to have numerous intrinsic connections and contained a significant number of labeled cells both above and below the injection site in each case. Other structures containing significant label in the midbrain and isthmus region included the nucleus subcuneiformis, the ventral tegmental area, the locus coeruleus and the parabrachial nuclei. The medullary and pontine reticular reticular formation provide the largest input to the periaqueductal gray from the lower brain stem. The midline raphe magnus and superior central nucleus also supply a significant fiber projection to the central gray. Both the trigeminal complex and the spinal cord provide a minor input to this region of the midbrain. The sources of afferent projections to the periaqueductal gray are extensive and allow this midbrain region to be influenced by motor, sensory and limbic structures. In addition, evidence is provided which indicates that the four subdivisions of the central gray receive differential projections from the brain stem as well as from higher brain structures.

Afferent Pathways↗
PubMed1993

Central nervous system innervation of the penis as revealed by the transneuronal transport of pseudorabies virus.

Transneuronal tracing techniques were used in order to identify putative spinal interneurons and brainstem sites involved in the control of penile function. Pseudorabies virus was injected into the corpus cavernosus tissue of the penis in rats. After a four day survival period, rats were perfused with fixative and virus-labelled neurons were identified by immunohistochemistry. Postganglionic neurons were retrogradely labelled in the major pelvic ganglia. In the spinal cord, sympathetic and parasympathetic preganglionic neurons were labelled transneuronally. Presumptive interneurons were also labelled in the lower thoracic and lumbosacral spinal cord in locations consistent with what is currently known about such interneurons. In the brainstem, transneuronally labelled neurons were found in the medulla, pons and hypothalamus. Regions consistently labelled included the nucleus paragigantocellularis, parapyramidal reticular formation of the medulla, raphe pallidus, raphe magnus, A5 noradrenergic cell group, Barrington's nucleus and the paraventricular nucleus of the hypothalamus. This study confirmed previous studies from our lab and others concerning the preganglionic and postganglionic neurons innervating the penis. The number, morphology and location of these neurons were consistent with labelling seen following injection of conventional tracers into the penis. The brainstem nuclei labelled in this study were also consistent with what is currently known about the brainstem control of penile function. The labelling appeared to be highly specific, in that descending systems involved in other functions were not labelled. These results provide further evidence that the pseudorabies virus transneuronal tracing technique is a valuable method for identifying neural circuits mediating specific functions.

Afferent Pathways↗
PubMed1988

The neurophysiology of vomiting.

Nausea and vomiting can be induced by a wide variety of stimuli such as pregnancy, space travel, raised intracranial pressure, radiation and cytotoxic drugs. The mechanisms by which all these diverse stimuli culminate in a final common act is unknown. From studies in the 1950s a model of the emetic reflex emerged consisting of a chemoreceptor trigger zone in the area postrema and a vomiting centre in the brain stem. This concept has been reviewed and revised in the light of recent studies. Many discussions of emesis involve detailed descriptions of the gastrointestinal events associated with the act of vomiting only-nausea and retching receiving little attention. Here we have tried to give a broader view by considering the neurophysiology of such events and have included nausea and retching, phenomena that are usually inseparable from vomiting. The possible biological function of these events is also discussed. The involvement of visceral systems (such as the heart, airways and gut) is included, and particular attention is paid to vagal mechanisms underlying the changes in gut motor activity. Emesis has long been thought to be organized by a 'vomiting centre'; the possibility that this vomiting centre could be the parvocellular reticular formation is reviewed, as is the concept that the 'centre' is larger than an anatomically defined single group of cells. The mechanism of action of two clinically relevant emetic stimuli--radiation and cytotoxic drugs-is considered in detail. Recent studies of the antiemetic properties of novel 5-HT-3 receptor antagonists against radiation and cytotoxic drug-induced vomiting are discussed; these studies suggest that important advances will be made in the treatment of emesis induced by these and other related agents.

Afferent Pathways↗
PubMed2004

Involvement of nuclei in the hypothalamus in cardiac sympathoexcitatory reflexes in cats.

The hypothalamus is considered to be an important area in the central regulation of cardiovascular function. However, its role in processing excitatory cardiovascular reflexes induced by stimulation of cardiac afferents has not been established. In the present study, using c-Fos immunoreactivity, we located neurons in the hypothalamus activated by inputs from cardiac sympathetic afferents. Following bilateral barodenervation and cervical vagotomy in anesthetized cats, bradykinin (BK, 1-10 microg, in 0.1 ml; n=7) was applied repetitively (6x, every 20 min) to the anterior epicardial surface of the left ventricle. This chemical stimulation caused consistent excitatory cardiovascular reflexes characterized by increases in blood pressure (BP) and heart rate (HR), while the vehicle for BK (0.9% saline, n=6) produced no such responses. Compared to control cats, c-Fos immunoreactive cells were significantly increased (P<0.05) in the arcuate nucleus (ARC), dorsal hypothalamic area (HDA), dorsomedial nucleus, paraventricular hypothalamic nucleus (PVN) and periventricular nucleus in the BK-treated animals. More neurons double-labeled with c-Fos and nitric oxide synthase (NOS) were observed in the PVN following epicardial application of BK (P<0.05). There was no significant increase in co-localization of these two labelings in the other nuclei. These results suggest that several nuclei in the hypothalamus respond to activation of cardiac sympathetic afferents, leading to sympathoexcitatory reflexes. Nitric oxide (NO) may function as a neurotransmitter or as a neuromodulator in the PVN during these cardiac-cardiovascular responses.

Afferent Pathways↗
PubMed2003

The effects of deafferentation and exogenous NGF on neurotrophins and neurotrophin receptor mRNA expression in the adult superior cervical ganglion.

Levels of nerve growth factor (NGF) and neurotrophin-3 (NT-3) protein and neurotrophin receptor mRNA in adult sympathetic neurons were investigated following surgical removal of preganglionic input and/or in vivo administration of NGF. Expression of trkC and p75, but not trkA, was significantly decreased following a 3-week deafferentation of the superior cervical ganglion (SCG). Protein levels of NGF and NT-3 in the SCG were unchanged by deafferentation. A 2-week intracerebroventricular infusion of NGF without deafferentation resulted in enhanced mRNA levels of trkA, trkC, and p75 as well as significantly increased NGF and NT-3 protein in the SCG. When NGF infusion followed deafferentation, both trkA and p75 showed significant increases while trkC levels were similar to control values. NGF protein was not increased in the SCG when deafferentation preceded exogenous NGF, yet NT-3 was elevated and levels were similar to cases receiving NGF infusion only. These results support a role for preganglionic input in trkC and p75 expression in adult sympathetic neurons. The increased levels of NT-3 protein and trkC gene expression observed following NGF infusion suggest that NGF influences NT-3 regulation in adult sympathetic neurons. In addition, the present findings provide evidence that, when preganglionic input is removed prior to the NGF infusion, NT-3 effectively competes with NGF for trkA binding. Taken together, we propose that NT-3 may play a role in the robust sprouting of sympathetic cerebrovascular axons previously observed following NGF administration, particularly when deafferentation precedes the NGF infusion period.

Afferent Pathways↗
PubMed2004

Control of bladder function by peripheral nerves: avenues for novel drug targets.

The micturition reflex involves afferent nerve activation when the bladder is sufficiently full and subsequent controlled firing of parasympathetic efferent nerves to contract the detrusor muscle as part of the voiding mechanism. Alteration of the sensitivity of afferent activation or loss of control over transmitter release could lead to sensory- or motor-activated incontinence, respectively. The control mechanisms that regulate these 2 activities remain poorly understood. Current opinion is that the sensation of bladder fullness is relayed by afferent nerves in the mucosal layer, which are activated by the release of chemical mediators, such as adenosine triphosphate (ATP), from the urothelium when it is stretched as the bladder fills. This hypothesis supports the concept that other chemical signals that affect bladder sensation (eg, changes in urine composition and agents such as capsaicin) can modulate the sensitivity of the basic system. It has also been proposed that a layer of myofibroblasts immediately below the basal lamina of the urothelium acts as a variable gain regulator of the sensory process between ATP release and afferent excitation. These myofibroblasts are functionally connected to form an electrical syncytium, make close contact with nerves, and respond by generating electrical responses and transient increases in intracellular Ca2+ when exposed to ATP. On the efferent side, using a guinea pig detrusor model, possible modulators of transmitter release have been investigated, including adenosine (the breakdown product of the neurotransmitter ATP). Adenosine reduces the force of nerve-mediated contractions by acting predominantly at presynaptic sites at the nerve-muscle junction via a subtype of an adenosine receptor-the A1 receptor. An additional effect, possibly via A2 receptors, is also present on the detrusor muscle itself. These actions of adenosine are less evident in human detrusor muscle but remain a potential modulatory target. In summary, the cellular and molecular regulation of bladder fullness sensation and efferent transmitter release are becoming better understood and represent potential drug targets for the management of detrusor overactivity.

Adenosine↗
PubMed2006

C2H2 zinc finger-SET histone methyltransferase is a plant-specific chromatin modifier.

Histone modification represents a universal mechanism for regulation of eukaryotic gene expression underlying diverse biological processes from neuronal gene expression in mammals to control of flowering in plants. In animal cells, these chromatin modifications are effected by well-defined multiprotein complexes containing specific histone-modifying activities. In plants, information about the composition of such co-repressor complexes is just beginning to emerge. Here, we report that two Arabidopsis thaliana factors, a SWIRM domain polyamine oxidase protein, AtSWP1, and a plant-specific C2H2 zinc finger-SET domain protein, AtCZS, interact with each other in plant cells and repress expression of a negative regulator of flowering, FLOWERING LOCUS C (FLC) via an autonomous, vernalization-independent pathway. Loss-of-function of either AtSWP1 or AtCZS results in reduced dimethylation of lysine 9 and lysine 27 of histone H3 and hyperacetylation of histone H4 within the FLC locus, in elevated FLC mRNA levels, and in moderately delayed flowering. Thus, AtSWP1 and AtCZS represent two main components of a co-repressor complex that fine tunes flowering and is unique to plants.

Amino Acid Sequence↗
PubMed1996

Nitric oxide and nitrovasodilators: similarities, differences, and interactions.

The endothelium functions as a semipermeable membrane separating the blood from the body and allowing the transport of macromolecules from the blood to the interstitial space. The endothelium secretes a number of diffusible substances. These include endothelium-derived relaxing factor (EDRF), endothelium-derived hyperpolarizing factor (EDHF), and prostacyclin, in addition to vasoconstrictors including endothelin, angiotensin, and endothelium-derived contracting factor. EDRF is now known to be nitric oxide, or a closely related molecule, which affects signaling by stimulation of soluble guanylate cyclase, causing increased intracellular levels of cyclic guanosine monophosphate (cGMP), in turn leading to relaxation of vascular smooth muscle as well as a variety of additional effects that include altered function of platelets and cardiac myocytes. Nitric oxide can be made available to cellular elements in two ways: by endogenous synthesis via one or more of the three nitric oxide synthases now known to exist in mammalian species; or by exogenous administration of pharmacologic sources of nitric oxide, usually as organic nitrate vasodilators that can be metabolically converted to biologically activated nitric oxide. This process appears to require free sulfydryl groups. The metabolic machinery necessary to convert organic nitrates to a biologically active form exists mainly in the vasculature and not in the myocardium. Numerous studies have demonstrated that the presence of coronary artery disease is associated with interruption of the endogenous production of nitric oxide. Under these circumstances, exogenous nitrates still produce coronary vasodilation as well as relaxation of vascular smooth muscle in the periphery. Other articles in this supplement will focus on the vascular effects of nitric oxide and nitrovasodilators; this article will conclude with a brief discussion of the role of the nitric oxide pathway in the control of cardiac autonomic responsiveness and the potential role of cytokines and the nitric oxide pathway to impair the ability of the myocardium to respond to catecholamines or other stimuli with a normal increase in contractile function.

Heart Failure↗