Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to determine if endothelium-dependent vasodilation is preserved in the spastic segment of the epicardial coronary artery. Segmental responses of the coronary artery to substance P were examined by the use of a quantitative angiographic technique in 21 patients with variant angina. Coronary diameter at the basal state did not differ between the spastic and the nonspastic segments (2.3 +/- 0.2 mm, 2.3 +/- 0.4 mm, p greater than 0.05). Changes in coronary diameter in response to substance P did not differ between segments with ergonovine-induced spasm and nonspastic segments. Maximal dilation averaged 27.1 +/- 9.5% in the spastic segment and 24.4 +/- 9.6% in the nonspastic segment (expressed as a percent increase over the value before drug administration). It appears that both the potential of the endothelium to release endothelium-dependent relaxing factor and the dilating response of the smooth muscle to endothelium-dependent relaxing factor are preserved, even in the spastic segment.
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PMID:Preservation of endothelium-dependent vasodilation in the spastic segment of the human epicardial coronary artery by substance P. 137 Oct 34

Endothelial dysfunction has been implicated as a cause of coronary vasospasm in patients with variant angina. This study aimed to determine if endothelium-dependent vasodilation evoked with substance P (SP) was altered at the spastic site where vasospasm was induced by acetylcholine (ACH) in patients with variant angina. It has been shown that SP evokes endothelium-dependent vasodilation with no direct effect on vascular smooth muscle in excised human coronary arteries. SP and ACH were infused into the coronary arteries in nine patients with variant angina in whom coronary arteriograms showed normal or mild atherosclerotic lesions. The vasomotor responses of coronary arteries were assessed by quantitative arteriography. ACH at a high dose (100 micrograms/min) provoked coronary vasospasm associated with anginal attack in all patients. In contrast, SP at graded doses (13.5, 40, and 135 ng/min) caused the dose-dependent and comparable increases in the coronary diameter at the spastic and control sites. ACH at a low dose (10 micrograms/min) also caused comparable vasodilation at the spastic and control sites in patients with normal coronary arteries. Coronary vasodilating responses to SP were comparable in patients with variant angina and those with atypical chest pain. The results indicate that endothelium-dependent vasodilation evoked with SP and ACH at the low dose was present at the vasospastic site in patients with variant angina. These findings suggest that the ACH-induced coronary vasospasm in patients with variant angina results from hyperreactivity of vascular smooth muscle to ACH but not from endothelial dysfunction.
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PMID:Preserved endothelium-dependent vasodilation at the vasospastic site in patients with variant angina. 137 74

We measured substance P-like immunoreactivity (SPLI), beta-endorphin-like immunoreactivity (BELI), acetylcholinesterase activity, and total protein content in pericardial fluid and plasma of patients with angina pectoris and patients with no angina pectoris. SPLI and BELI levels, acetylcholinesterase activity, and total protein content were determined by radioimmunoassay, a colorimetric method, and by the method of Lowry et al. (J Biol Chem 1951; 193:265-75), respectively. In the pericardial fluid, patients with angina had SPLI, BELI, acetylcholinesterase, and total protein values of 1.69 +/- 0.23 fmol/mg protein, 0.16 +/- 0.13 fmol/mg protein, 0.06 +/- 0.02 units, and 25.7 +/- 3.2 mg/ml, respectively. Patients with no angina had SPLI, BELI, acetylcholinesterase, and total protein values of 0.93 +/- 0.17 fmol/mg protein, 0.19 +/- 0.10 fmol/mg protein, 0.16 +/- 0.02 units, and 44.6 +/- 5.3 mg/ml, respectively. SPLI levels were significantly higher (p less than 0.03), and acetylcholinesterase (less than 0.002) and total protein content (less than 0.004) were significantly lower in the pericardial fluid of patients with angina when compared with those of patients with no angina. BELI levels were not significantly different between the two groups. In the plasma, no significant differences were found in SPLI, BELI, acetylcholinesterase, and total protein values between the two groups of patients. Patients with angina had SPLI, BELI, acetylcholinesterase, and total protein values of 0.47 +/- 0.26 fmol/mg protein, 0.06 +/- 0.06 fmol/mg protein, 0.29 +/- 0.15 units, and 68.2 +/- 8.7 mg/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substance P, acetylcholinesterase, and beta-endorphin levels in the plasma and pericardial fluid of patients with and without angina pectoris. 170 48

The tone of isolated segments of human coronary arteries with manifestations of atherosclerotic lesions was increased by serotonin (10(-6) M) or prostaglandin F2 alpha (10(-6) M). Insignificant endothelium-dependent relaxation induced by bradikinin, calcium ionofore A-23187 or substance P was observed in several segments with marked (plaque) as well as macroscopically invisible sclerotic lesion. Segments of human coronary arteries without sclerotic damage demonstrated endothelium-dependent relaxation in response to activators of endothelial relaxation factor. Functional disturbance of coronary artery endothelium in endothelial relaxation factor production may be one of the causes of increased smooth muscle tonic contractions, responsible for coronary artery spasm underlying angina pectoris and myocardial infarction.
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PMID:[Endothelial function and spasm of the coronary artery]. 342 12

This study aimed to determine whether or not endothelium-dependent vasodilation is preserved in spastic segments of human epicardial coronary arteries. Segmental responses of coronary arteries to substance P were examined in 30 patients with variant angina and in 10 patients with atypical chest pain using a quantitative angiographic technique. Coronary diameter at the basal state was matched between spastic and non-spastic segments in patients with variant angina, normal coronary arteries and with atypical chest pain (2.3 +/- 0.2 mm, 2.3 +/- 0.4 mm, 2.4 +/- 0.3 mm, respectively). In segments where vasospasm was induced by ergonovine and/or acetylcholine, changes in diameter in response to substance P did not differ from those in non-spastic segments; maximal dilation averaged 27.1 +/- 9.5% in the spastic segments and 24.4 +/- 9.6% in the non-spastic segments (expressed as a percent increase over the value before drug administration). It would appear that the potential of the endothelium to release endothelium-dependent relaxant factor (EDRF) and the vasodilator response to EDRF are preserved, even in spastic segments.
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PMID:Preserved endothelial function in the spastic segment of the human epicardial coronary artery in patients with variant angina--role of substance P in evaluating endothelial function. 750 36

Electrical spinal cord stimulation (SCS) is an important method in the treatment of certain chronic pain syndromes which are difficult to manage with conventional techniques. The indications for this procedure have gradually narrowed to neuropathic pain states, especially those of peripheral origin, ischaemic pain due to peripheral vascular disease, and treatment-resistant angina pectoris. In spite of the clinical use of this method for more than 20 years, the mechanisms underlying the pain alleviating effect remain largely unknown. For the effect on ischaemic pain, recent animal research indicates a mediation via autonomic pathways. Concerning the effect on neuropathic pain progress in knowledge has been scanty. Data from spinal microdialysis in decerebrated or anaesthetized animals indicate the possible importance of serotonin and substance P in the dorsal horn for pain inhibition by SCS. However, data from experiments on anaesthetized animals are, for several reasons, not likely to truely reflect the mechanisms active in conscious humans under treatment with SCS. To avoid the influence of anaesthesia and to approach the clinical situation, we have developed an animal model enabling simultaneous SCS and supraspinal microdialysis in awake, freely moving rats. The animal model is described and some preliminary data indicating a release of gamma-amino butyric acid (GABA) induced by SCS in the periaqueductal grey matter (PAG), are presented.
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PMID:An animal model for the study of brain transmittor release in response to spinal cord stimulation in the awake, freely moving rat: preliminary results from the periaqueductal grey matter. 790 75

The vascular endothelium is the site of formation of several powerful mediators. One of these is NO, a chemically unstable radical formed by enzymatic conversion of L-arginine in the presence of molecular oxygen. NO elicits relaxation of VSMC by activating cytosolic guanylate cyclase. NO also counteracts platelet adhesion and aggregation. The biological actions of NO make it a key substance in the endogenous defense against vascular occlusion and thrombosis. The basal formation of NO maintains a moderate but significant vasodilation in the systemic resistance vessels and counteracts platelet activity. When blood flow in conduit arteries is increased there is an augmented endothelial formation of NO, eliciting flow-dependent vasodilation. Beside this, several vasodilators (acetylcholine, bradykinin, histamine, substance P) operate by stimulating endothelial NO formation. On the other hand, drugs like nitroglycerin and papaverine operate independently of the vascular endothelium. Vasodilator mechanisms, physiological as well as pharmacological, may therefore be characterized as endothelium-dependent (i.e. NO-mediated), or endothelium-independent (i.e. not mediated by NO). Physiologically, mixed mechanisms occur. Failure of the vascular endothelium to elicit NO-mediated vasodilatation may be due to decreased formation, increased degradation, decreased sensitivity to the NO formed, or a mixture of these factors. Irrespective of the mechanism behind, this is referred to as endothelial dysfunction. Endothelial dysfunction occurs in several cardiovascular settings, like atherosclerosis, hypercholesterolaemia, diabetes, and essential hypertension. Endothelial dysfunction leads to an impaired tissue perfusion, increased local vascular resistance, decreased defense against thrombus formation, and possibly also decreased defense against hypertrophy of the VSMC in the vessel wall media. In patients with CHD, endothelial dysfunction leads to an impaired coronary flow response to physical and mental stress, and to promotion of platelet adherence and aggregability. Endothelial dysfunction is thereby a probable aggravating factor in the atherosclerotic process, adding a functional component on top of the structural lesions characterizing this disease. A particular form of endothelial dysfunction, limited to the arterial resistance vessels, may explain the symptoms and clinical characteristics of microvascular angina. In patients with essential hypertension, endothelial dysfunction prevails, adding a functional component to the structural factors also in this disease. Hitherto, the only therapeutic tools available to restore endothelial dysfunction appear to be restriction of the dietary intake of lipids, possibly reinforced with intake of antioxidants like fish oil and vitamin E. However, large clinical trials to confirm the efficacy of such therapy in reversing endothelial dysfunction have not been conducted. In the future, more directly acting therapeutic regimens, aimed at supporting or substituting the endogenous formation of NO, are likely to appear as well.
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PMID:Endothelial nitric oxide and cardiovascular disease. 815 Dec 63

Several clinical characteristics of angina pectoris are reflected in the nature of the cardiac nervous system. The extent of silent ischemia, the slow onset of angina during the ischemic cascade, the diffuse character of the visceral component of the pain and the referred pain. Of putative myocardial pain messengers so far only adenosine fulfills Lewis criteria for a cardiac pain messenger. Dependent on the pattern of ischemic release, adenosine appears to stabilize or sensitize afferent cardiac nerves with silent or painful ischemia as a result. Through spatio-temporal summation sensitization may result in an alarm whereby the myocardium signals centrally its precarious state. The activity of adenosine-sensitized afferent nerves may become enhanced by additional stimuli such as potassium, protons, substance P and bradykinin. Primary and secondary afferents from the intrinsic and extrinsic intrathoracic cardiac nervous systems project towards the central nervous system via sympathetic and vagal elements. The main part of primary afferents have their cell bodies in extrinsic cardiac ganglia and only a minority in the dorsal root ganglia. No cardiotopical representation exists in the intrathoracic ganglia. The majority of neurons in intrinsic and extrinsic cardiac ganglia are interneurons integrating cardiac inotropic and vasomotor functions on a beat to beat basis. Multisynaptic transmission over secondary afferents may not only delay the anginal pain message; as somatic afferents also connect to the intrathoracic ganglia, these multisynaptic transmissions may also be a basis for referred pain or pain inhibition. Dorsal root afferents appear to convey only excitatory impulses. Probably due to interneurons, cardiac nodose ganglia activities can become either excitatory or inhibitory. Cardiocardiac reflexes occur from the axonal level up to the brain stem cerebral levels. The brain defense system including the basal ganglia and limbic system and the prefrontal but not the sensory cortex are activated during myocardial ischemia indicating its traumatic nature. The reflexogenic nature of angina pectoris is evident as in silent ischemia similar central nervous system activation occurs as in angina pectoris but with less intense prefrontal activation while in Syndrome X more intense activation occurs. Therapeutic interference of the reflex mechanism by sympathectomy, electrical stimulation or pharmacological interventions can counteract angina pectoris and relax the reflexogenic stress and vasomotor drive on the heart.
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PMID:Neurophysiological aspects of angina pectoris. 910 85

At the turn of this century, it was proposed that ischemic cardiac pain might be related to distension of the ventricular wall ("mechanical hypothesis"). Three decades later, it was hypothesized that ischemic pain might be elicited by the intramyocardial release of pain-producing substances induced by ischemia ("chemical hypothesis"). Studies carried out in the past 10 years have given strong support to the chemical hypothesis, because they have consistently shown that adenosine is a mediator of ischemic cardiac pain. Adenosine-induced ischemic cardiac pain is mediated primarily by stimulation of A1 receptors located in cardiac nerve endings and is potentiated by substance P. Conversely, the magnitude and rate of left ventricular dilation during ischemia do not predict the severity of angina. It is worth noting, however, that stretching of epicardial coronary arteries appears to potentiate the severity of angina caused by myocardial ischemia. The nervous activity generated by myocardial ischemia is modulated in intrinsic cardiac, mediastinal, and thoracic ganglia. Then it is further modulated in the central nervous system and projects bilaterally to the cortex, as demonstrated in humans by positron emission tomography, where it is decoded as a painful sensation. The causes responsible for the lack of angina during myocardial ischemia are probably different in patients who present both pain-free and painful myocardial ischemia, in patients with predominantly painless ischemia, and in diabetic patients.
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PMID:New look to an old symptom: angina pectoris. 939 81

Calcitonin gene-related peptide (CGRP) and substance P co-exist in capsaicin-sensitive primary sensory neurons and are released from the myocardium after activation of sensory nerve fibres as well as by ischemia in animals. This study was undertaken to try to clarify the potential involvement of immunoreactive (ir) CGRP in anginal pain and myocardial ischemia in humans. One clinical group (n = 87) and one experimental group (n = 14) were studied. The clinical group was admitted to a coronary care unit with suspected or definite acute myocardial infarction (AMI). The experimental group consisted of patients with severe angina pectoris (NYHA III-IV). This group was subjected to atrial pacing up to the appearance of angina pectoris. Mean irCGRP levels at admission for the clinical group with and without AMI showed no significant difference. Neither were any significant differences found in irCGRP concentrations between patients with pain as compared to those without pain or in the group who had had chest pain >30 min before hospital admission as compared to those with chest pain <30 min. Extraction ratios for lactate and irCGRP was calculated in the experimental group. No statistically significant covariance was found between irCGRP extraction ratio and lactate extraction ratio (r(xy) = -0.006) at the time of appearance of angina during atrial pacing. Despite the facts that CGRP may be liberated by a variety of physiological stimuli and may act as a potent vasodilator in the human vasculature, no evidence has been found in this study that CGRP release is increased as a consequence of ischemia or ischemic pain.
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PMID:Acute ischemic chest pain is not associated with increased calcitonin gene-related peptide (CGRP) levels in peripheral plasma nor in the coronary circulation. 1054 Sep 19


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