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)

Plasma levels of a variety of hormones have been measured in patients within two hours of the onset of symptoms of myocardial infarction and before commencement of any treatment. Increased plasma concentrations were found for norepinephrine, epinephrine, glucagon, aldosterone, vasopressin, atrial natriuretic peptide, corticotrophin, prolactin, cortisol and substance P while plasma renin activity was raised. The plasma concentrations of insulin, growth hormone, neurotensin, bombesin and vasointestinal peptide were normal.
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PMID:Hormonal response in untreated myocardial infarction. 210 97

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

Immunocytochemical studies on lumbar dorsal root ganglia obtained at routine postmortem 24-36 h after death were carried out, and neuronal cross-sectional areas measured. The subjects were elderly (76-81 years), of both sexes, had died from heart attack or haemorrhage, and had no clinical evidence of clinical neuropathy or of disease known to be associated with neuropathy. The data were consistent between ganglia from the three subjects. There were striking similarities with data from other species. Two populations of cell profiles with overlapping size distributions were distinguished with an anti-neurofilament antibody, neurofilament-rich (45% of cell profiles) with a large mean area and neurofilament-poor with a smaller mean area. Anti-substance P and anti-peripherin antibodies both labelled a population with a small mean area, with extensive co-localization between them. There were also some differences between these human dorsal root ganglia and dorsal root ganglia from some other species. More neuronal profiles were labelled for substance P in humans (44%) than in rat (20%). More neuronal profiles were labelled for SSEA4 (stage specific embryonic antigen 4) in human (40.5%) than in rat dorsal root ganglia (10%), and the SSEA4-positive profiles were relatively smaller in human than in rat. No selective accumulation of lipofusin in profiles of large cells was apparent. This study also shows that quantitative morphometric analysis of immunocytochemically labelled dorsal root ganglion neuronal profiles can be carried out successfully on human sensory ganglia obtained at post-mortem. This is the first demonstration of the two main subgroups of dorsal root ganglia neurones with neurofilament-rich and poor somata in human tissue. The size distributions of neurons with neurofilament, substance P and peripherin are consistent with these neuronal populations having similar functional properties to those described in other species. From the known sensory and fibre loss with aging, it is speculated that the loss of some large diameter neurones with myelinated fibres and low mechanical thresholds, might account for the high percentage of neurones expressing substance P.
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PMID:Substance P, neurofilament, peripherin and SSEA4 immunocytochemistry of human dorsal root ganglion neurons obtained from post-mortem tissue: a quantitative morphometric analysis. 752 99

1. Venous resistance contributes very little to total peripheral resistance; more than half of the total blood volume, however, is contained in the extrathoracic veins. Owing to marked differences between venous and arterial anatomy and physiology, studies on veins and arteries usually require different methodological approaches. Whereas for arteries the most relevant parameters are resistance, pressure and flow, for veins volume and compliance are most important. For studies of general aspects of the peripheral circulatory system, venous occlusion plethysmography is probably the most useful method. The determination of both the rate of rise in limb volume and the total volume rise after inflating a proximally applied occlusion cuff to a subdiastolic pressure permits the concomitant estimation of both arterial flow and venous compliance. 2. Studies of direct pharmacological or physiological effects on veins, interactions of various pharmacological or physiological stimuli, or pathophysiological changes in venous responsiveness have been facilitated by the development of investigational techniques relying on direct measurements of the compliance of single human veins in vivo. One of these, relying on the use of a linear variable differential transformer (LVDT) for determining changes in the compliance of superficial veins at a standardized congestion pressure, has been found very suitable for the practical application in both patients and healthy subjects. 3. Physiological studies were carried out on the effect of age, exercise, temperature, and the menstrual cycle on venous compliance and venous responsiveness to various stimuli. In addition, interindividual variability in venous responsiveness in monozygotic and dizygotic twins and in unrelated subjects was investigated, and studies on the function of the endothelium were carried out in man in vivo. 4. Pathophysiological studies using this technique were reported from patients with hypertension, orthostatic hypotension, myocardial infarction, varicosis, cystic fibrosis, asthma, diabetes, systemic sclerosis, and cluster headache. 5. Clinical pharmacological studies represent a most important field for the use of this method. Studies were carried out on the effects of a large number of constrictor and dilator agents, and also on drug interactions on human veins in vivo. Venoconstriction was observed after local administration of alpha-adrenoceptor and 5-HT-receptor agonists, ergot derivatives, angiotensinogen, angiotensin I and II, and several prostaglandins. 6. Owing to the low venous tone present under effects can usually be quantified only on veins e.g. noradrenaline or 5-hydroxytryptamine. Under these conditions dilatation was observed after the administration of beta-adrenoceptor agonists, cholinergic (muscarinic) agonists, nitrates, calcium antagonists, bradykinin, substance P and several prostaglandins.
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PMID:Clinical pharmacology, physiology and pathophysiology of superficial veins--1. 782 19

Occlusion of aortocoronary venous grafts can be due to thrombosis, atherosclerosis, or vasospasm. Investigations have focused on properties of the graft itself, and little is known about the vascular reactivity and function of the native arteries proximal and distal to the vein graft, although spasm of the native artery distal to the graft site has been observed in patients. We hypothesized that the function of the endothelium of the native arteries may be altered after surgery. Autogenous venous grafts were placed in femoral arteries of rabbits to study the reactivity of the native arteries after grafting. Four weeks after graft implantation, the vein graft, ipsilateral vein, and native artery proximal and distal to the graft were removed for in vitro studies. Morphological evaluation by scanning electron microscopy and fluorescence microscopy after labeling with acetylated low density lipoprotein labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate indicated the presence of an intact, metabolically active endothelial layer. There was no alteration in the contractile responses to phenylephrine of the arteries, vein grafts, or veins. Precontracted vein grafts, veins, and arterial segments proximal to the grafts relaxed when exposed to endothelium-dependent vasodilators (acetylcholine, arachidonic acid, and substance P), but the native arteries distal to the grafts did not. In bioassay cascade experiments, the distal artery did not release any measurable relaxing factor when exposed to acetylcholine. We conclude that the endothelium of the distal artery did not function normally. The extent and reversibility of altered endothelial function remain to be determined. This observation may help to explain the occurrence of myocardial infarction after aortocoronary bypass grafting in some patients.
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PMID:Alteration of reactivity of native arteries induced by venous graft placement. 841 86

The first goal of this study was to test the hypothesis that chronic myocardial infarction alters reactivity of rat skeletal muscle arterioles in vivo. At 4, 8, and 16 wk after induction of chronic myocardial infarction or sham (control) surgery, the spinotrapezius muscle was prepared for direct visualization of the microcirculation. Responses of third-order arterioles (37.9 +/- 0.9 microns) were measured after topical suffusion of acetylcholine (ACh; 0.1, 1.0, and 10 microM), calcitonin gene-related peptide (CGRP; 0.01, 0.1, and 1.0 nM), substance P (SP; 0.01, 0.1, and 1.0 microM), and sodium nitroprusside (SNP; 1.0, 10, and 100 microM). Arteriolar reactivity was impaired after chronic myocardial infarction in response to ACh and CGRP at all time periods examined. In contrast, vasodilatation in response to SP and SNP was preserved after 4, 8, and 16-wk of chronic myocardial infarction. The second goal of this study was to explore the possibility that impaired arteriolar reactivity during chronic myocardial infarction may be related to an altered availability of L-arginine (L-Arg). Suffusion of L-Arg (1.0 mM) partially restored impaired ACh- and CGRP-induced responses in myocardial-infarcted animals toward that observed in controls. Thus the present study demonstrates that impaired reactivity of skeletal muscle arterioles during chronic myocardial infarction appears to be partially related to an alteration in L-Arg availability.
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PMID:Effect of chronic myocardial infarction on in vivo reactivity of skeletal muscle arterioles. 917 11

Hypertension is an important risk factor for the development of atherosclerosis. Traditional antihypertensive therapy is not fully effective in prevention of cardiovascular abnormalities of hypertension. Two classes of hypotensive drugs, calcium antagonists and angiotensin-converting enzyme (ACE) inhibitors, reduce atherosclerosis in several experimental models in animals. Anti-atherosclerotic effects of calcium antagonists include attenuation of endothelial dysfunction, prevention of LDL modification, stimulation of LDL receptor activity, inhibition of superoxide radical generation and inhibition of vascular smooth muscle cells proliferation and migration. In large angiographic trials calcium antagonists reduced the development of new atherosclerotic plaques. ACE inhibitors also lead to the lower incidence of atherosclerosis in experimental animals. They inhibit migration and proliferation of vascular smooth muscle cells, reduce macrophage-derived foam cell accumulation, preserve protective endothelium function, reduce LDL modification and increase fibrinolytic activity. It depends on reduced angiotensin II synthesis, increased concentration of kinins, substance P and angiotensin-(1-7), inhibition of leukotriene B4 formation and improvement of insulin action. In some studies they also reduce plasma lipids concentration, including lipoprotein (a). ACE inhibitors were found to be ineffective in prevention of restenosis after PTCA in human but data derived from large, multicenter trials indicate that they are effective in the secondary prevention of myocardial infarction.
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PMID:[Anti-atherosclerotic action of hypotensive drugs]. 924 14

The D allele of the insertion (I)/deletion (D) polymorphism in the angiotensin-converting enzyme (ACE) gene and the C allele of the A1166-C polymorphism in the angiotensin II type 1 receptor (AGT1R) gene have been associated with altered vascular structure and with an increased risk of myocardial infarction. The aim of this study was to determine whether differences in vascular function could be demonstrated to link the previously described changes in structure and the disease outcome. 70 subjects were recruited at random from patients undergoing colonic resection, resistance arteries were excised and were mounted in a small vessel wire myograph. Vasomotor responses to potassium chloride, noradrenaline, prostaglandin F(2alpha), angiotensin I, angiotensin II, acetylcholine and substance P were performed in 30 subjects. Genotype was established in a blinded fashion after completion of myography. To exclude the possibility of masking of genetic influence by non-ACE conversion of angiotensin I, vasomotor responses were then performed to proline(10)-angiotensin I in a further 30 subjects and to angiotensin I in the presence of chymostatin in a further 10 subjects. No significant effect of the I/D polymorphism of the ACE gene was seen on vasomotor function. The C allele of the AGT1R gene was associated with an increase in sensitivity to prostaglandin F(2alpha) but not with alteration to the other vasoactive agents studied. The I/D ACE and A1166-C AGT1 receptor polymorphism do not appear to result in differences in vasomotor function in isolated human mesenteric resistance arterioles in subjects without evidence of underlying hypertensive or cardiovascular disease.
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PMID:Human vascular reactivity and polymorphisms of the angiotensin-converting enzyme and the angiotensin type 1 receptor genes. 1062 20

A subpopulation of capsaicin-sensitive cardiac C-fibre afferents co-store calcitonin gene-related peptide (CGRP), substance P and neurokinin A. CGRP exerts positive inotropic and chronotropic effects and is one of the most potent endogenous vasodilators yet discovered. A number of endogenous agents and conditions cause activation of cardiac C-fibre afferents with subsequent local release of CGRP. In myocardial ischaemia with its clinical manifestations angina pectoris and infarction, C-fibre afferents not only convey the sensation of pain, but there is also a local 'efferent' release of CGRP in the heart. After being released, CGRP causes coronary vasodilatation and attenuates the development of myocardial infarction. CGRP may thus represent an endogenous local myocardial protective substance with interesting clinical implications.
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PMID:Potential of calcitonin gene-related peptide in coronary heart disease. 1062 36

Actions mediated by the renin-angiotensin system may be inhibited at various levels: renin itself may be inhibited, angiotensin-I (A-1) conversion to angiotensin-II (A-II), or binding of A-II at the A-II type 1 (A-II1) receptor. The angiotensin-converting enzyme (ACE) inhibitors and the A-II1 receptor antagonists are now clinically established. Because ACE is a relatively unspecific peptidase which catalyses the breakdown of A-I, bradykinin and neuropeptides like substance P and neurotensin, the effects of ACE inhibitors go far beyond the prevention of A-II production. On the other hand, in certain tissues like vascular and cardiac tissue, A-II is produced by other enzymes, for instance chymase, and ACE inhibitors do not consistently prevent A-II production. The action of A-II1 receptor antagonists may also not be confined to prevention of binding of A-II at the A-II1 receptor, as by rebound more A-II may bind at the A-II type 2 (A-II2) receptor and thus mediate until now not well defined effects. Thus, anti-ischemic actions of these drugs may be related to multiple mechanisms. Inhibition of A-II effects at the A-II1 receptor may prevent systemic and coronary vasoconstriction and growth effects of A-II on various cell types. In addition, A-II may potentiate, by pre- and postsynaptic mechanisms, activation of the sympathetic nervous system. Prevention of breakdown of bradykinin, substance P and neurotensin may result in direct vasodilation or release of nitrous oxide from the endothelium. Thus, growth-inhibiting effects may also be mediated. All these mechanisms seem to direct to a reduction of cardiac load by vasodilation and to a limitation of cardiovascular cell growth. While the systemic circulating renin-angiotensin system is probably responsible for control of cardiac load, local systems seem to control cell growth. Systemic effects seem to depend on activation of the renin-angiotensin system which has been shown in various ischemic syndromes. Activation of various components of the renin-angiotensin system has been demonstrated in myocardial ischemia, acute myocardial infarction and coronary occlusion and reperfusion models as well as in chronic left ventricular dysfunction post-myocardial infarction. While animal models of stress-induced myocardial ischemia have revealed predominantly positive results, clinical studies, which mostly were small and not well controlled, were equivocal. Large clinical trials with ACE inhibitors in acute myocardial infarction showed small benefits over placebo. Hypotension seems to be a critical side-effect in this situation. Experimental models show protective effects of both ACE inhibitors and A-II1 receptor antagonists in the situation of ischemia and reperfusion. New data on large clinical trials in patients at risk of cardiovascular events but normal left ventricular function demonstrate clear benefits of an ACE inhibitor. Large clinical trials in patients with chronic left ventricular dysfunction post-myocardial infarction show reduction of ischemic events.
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PMID:Anti-ischemic potential of drugs related to the renin-angiotensin system. 1139 74


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