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

Static muscular contraction has been shown to increase cardiovascular and ventilatory function in reflex manner. The sensory arm of this reflex arc is comprised of group III and IV muscle afferents. The discharge properties of these muscle afferents whose activation causes the pressor reflex response to contraction were investigated. Group III afferents were more responsive to mechanical stimuli, such as tendon stretch and probing their receptive fields than were group IV afferents. In contrast, group III afferents were less responsive to ischemic contraction than were group IV afferents. Equal percentages of group III and IV afferents were stimulated by potassium, lactic acid and arachidonic acid, each of which are metabolic products of contraction. Adenosine, phosphate and lactate, however, had no effect on the discharge of the afferents. Intrathecal injection of antagonists or antibodies to substance P and somatostatin attenuated the pressor response to contraction by about half, a finding that suggests a role for these 2 peptides in the spinal transmission of the reflex.
Am J Cardiol 1988 Sep 09
PMID:Pressor reflex response to static muscular contraction: its afferent arm and possible neurotransmitters. 245 28

Endothelin, a 21 amino acid peptide synthesized by cultured porcine aortic endothelial cells, has recently been identified and shown to produce a potent and prolonged constriction of mammalian blood vessels in vitro. Using tissue obtained from explanted hearts at the time of cardiac transplantation, the response of isolated human epicardial coronary arteries to endothelin was studied. The presence of endothelin binding sites was demonstrated in these vessels using an autoradiographic technique. Endothelin produced a dose-dependent increase of tension in the isolated coronary vessels with a maximal tension achieved equal to 135% of that induced by 90 mM of potassium. The maximal response was slow to develop and had a prolonged duration of 15 to 20 minutes. Nicardipine (4 microM) failed to affect the contraction induced by low doses of endothelin, but decreased the tension obtained at high doses. However, adenosine, substance P and glyceryl trinitrate were all effective in reversing the contraction induced by endothelin, while indomethacin and acetylcholine were ineffective. These features differ from those of other endogenous constrictor agents and make endothelin a potential candidate for long-term modulation of vascular tone.
Am J Cardiol 1989 Jun 01
PMID:Influence of endothelin on human coronary arteries and localization of its binding sites. 265 27

In the last few years, experimental evidence has accumulated which suggests a substantial role for the endothelium in the control of vascular tone. Endothelium-dependent dilatations have been demonstrated in various arteries of numerous mammalian species including man. Among the stimuli which elicit endothelium-dependent dilatation are such varying stimuli as increases in blood flow and hypoxia, as well as endogenous (acetylcholine, ATP, ADP, bradykinin, substance P) and pharmacological agents (calcium ionophore A 23187, ergometrine, hydralazine, melittin). The functional importance of endothelium-dependent dilatation is emphasized by the fact that the direct vasoconstrictor effects of some of these substances (acetylcholine, histamine, norepinephrine, serotonin) on vascular smooth muscle is attenuated or even reversed by their simultaneous stimulatory effect on endothelial cells, resulting in the release of a vasodilator signal. Bioassay experiments have shown that a humoral vasodilator agent with a biological half-life in the range of seconds is released from the endothelium (native or cultured) during stimulation with acetylcholine, ATP and calcium ionophore. Experimental data are presented, which suggest that EDRF may act by direct stimulation of guanylate cyclase, resulting in smooth muscle relaxation due to increased smooth muscle cyclic GMP levels. The chemical nature of this nonprostaglandin endothelium-derived relaxant factor (EDRF) is still not known. The possible physiological and pathophysiological significance of endothelium-dependent dilatation in situ is discussed. Special attention is paid in this context to the potential role of EDRF activity in coronary vasomotor control.
Basic Res Cardiol
PMID:The role of endothelium in the control of vascular tone. 300 Mar 43

Sixteen patients with metastatic carcinoid tumors of ileal or cecal origin were studied in order to evaluate the frequency and degree of cardiac involvement in a nonselected patient group. We have also studied the correlation between plasma hormone levels (e.g., 5-hydroxytryptamine (5-HT) and substance P) and the degree of cardiac involvement. The patients underwent physical examinations, electrocardiograms, chest x-rays, cardiac catheterization, and echocardiography. Plasma levels of 5-HT and substance P were analyzed. Carcinoid heart involvement was found in 3 of 16 patients (19%) but no patient had subjective symptoms associated with heart disease. Four patients (25%) had slight pulmonary hypertension. No left-sided heart lesions were seen. No correlation between blood levels of 5-HT or substance P and heart involvement was found. Eight patients died during the follow-up period, but in none of these was the cause of death cardiac failure. Carcinoid heart disease is not as common in our patients as in patients selected on a cardiological basis described in earlier studies. Echocardiography appears to be the most efficient technique for detection of even subclinical heart involvement and a useful tool for following its progress.
Clin Cardiol 1986 Jan
PMID:Heart involvement in metastatic carcinoid disease. 394 30

1. An enzyme which can be extracted from brain inactivates nerveside in the optimum pH range 5.8-7.0.2. The polybasic acids trypan blue and its analogue trypan red, bromphenol blue and its analogue bromthymol blue at concentrations of 0.22 mM and ethylenediaminetetra-acetic acid (EDTA) at a concentration of 1 mM are strong inhibitors of the enzyme.3. Penicillin which is a monobasic carboxylic acid also inhibits the enzyme but only if concentrations as high as 3.6 mM are used. The antibiotic streptomycin which is a basic substance does not inhibit the enzyme.4. Caffeine at a concentration of 7.2 mM only weakly inhibits the enzyme.5. Chymotrypsin and wheat germ acid phosphatase also inactivate nerveside at pH 5.9 and are inhibited by the acidic dyes and penicillin. EDTA inhibits wheat germ phosphatase but activates chymotrypsin.6. Inactivation of nerveside by the brain enzyme and by wheat germ phosphatase is different from the action of chymotrypsin. Nerveside solutions incubated with chymotrypsin completely lose all biological activity whereas if incubation is carried out with either the brain enzyme or wheat germ acid phosphatase a residual biological activity remains even when the concentration of these two enzymes is increased. This residual biological activity is due to a peptide as it is destroyed by chymotrypsin.7. The manner in which nerveside is inactivated by the brain enzyme is uncertain as the preparation of the latter contained phosphodiesterase and protease activities which were similarly inhibited by the acid dyes, penicillin and EDTA.8. Pentylenetetrazole, picrotoxin, strychnine and tetanus toxin do not inhibit the brain enzyme.9. The nerveside-inactivating enzyme is not identical with the Substance P-inactivating enzyme in brain as the former is inhibited by EDTA while the latter is not.
 ...
PMID:The inhibitory effect of convulsant agents on the enzyme in brain which inactivates nerveside. 439 Mar 85

Patients with hypercholesterolemia have impaired endothelium-dependent vasodilation. However, previous human studies have invariably used muscarinic agents to assess endothelial function. The purpose of this investigation was to determine whether impaired endothelium-dependent vasodilation of hypercholesterolemic patients is related to a specific and isolated defect of the muscarinic receptor, or to a broader abnormality of the endothelial cells. The forearm vascular responses to the endothelium-dependent agents acetylcholine (7.5, 15, and 30 micrograms/min) and substance P (1, 2, and 4 pmol/min), and to the direct smooth muscle dilator sodium nitroprusside (0.8, 1.6, and 3.2 micrograms/min) were studied in 16 hypercholesterolemic patients (8 men and 8 women; age [mean +/- SD] 50 +/- 7 years; serum cholesterol > 250 mg/dl) and 16 normal volunteers (8 men and 8 women; age 47 +/- 8 years; serum cholesterol < 200 mg/dl). Drugs were infused into the brachial artery and the response of the forearm vasculature was measured by strain-gauge plethysmography. The vasodilator response to acetylcholine was reduced in hypercholesterolemic patients compared with normal controls; at the highest dose (30 micrograms/min) the increase in forearm blood flow was 13.5 +/- 7 ml/min/100 ml in controls and 7.54 +/- 6 in patients (p < 0.05). The response to substance P was also blunted in hypercholesterolemic patients; at the highest dose (4 pmol/min), the increase in forearm blood flow was 12.1 +/- 5 ml/min/100 ml in controls and 7.6 +/- 4 in patients (p < 0.03). A significant correlation was found between the highest blood flow responses with acetylcholine and with substance P (r = 0.58; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Cardiol 1995 Jan 01
PMID:Impaired endothelium-dependent vascular relaxation in patients with hypercholesterolemia extends beyond the muscarinic receptor. 752 64

The purpose of this study was to determine the effects of bradykinin (BK), substance P (SP) and histamine on plasma exudation in the skin of conscious dogs with and without pacing-induced heart failure. We also determined the role tissue angiotensin I-converting enzyme (ACE) and neutral endopeptidase (NEP) play in modulating these responses. We found that intradermal injection of BK, SP and histamine induced a significant, concentration-dependent Evans blue exudation in normal dogs (p < 0.05). Bradykinin-induced responses were significantly potentiated by captopril (p < 0.05). In contrast, phosphoramidon potentiated BK-induced responses only at low concentrations of BK. Both captopril and phosphoramidon had no significant effects on SP- and histamine-induced Evans blue exudation. BK- and SP-induced responses were significantly attenuated, whereas histamine-induced Evans blue exudation was significantly potentiated in dogs with heart failure. We conclude that heart failure is associated with attenuation of BK- and SP-, but not histamine-induced plasma exudation in the peripheral microcirculation and that these responses are not modulated by tissue ACE and NEP.
Basic Res Cardiol
PMID:Plasma exudation in conscious dogs with experimental heart failure. 753 20

Nitric oxide released by cardiac endothelial cells modulates myocardial contractile function through elevation of intracellular 3',5'-cyclic guanosine monophosphate (cGMP). In the absence of agonist stimulation, nitric oxide typically enhances myocardial relaxation and reduces diastolic tone, without significantly altering the rate of force or pressure development. This pattern of effect is observed with nitric oxide or with cGMP analogues in isolated rat cardiac myocytes, isolated ferret papillary muscle preparations, and isolated ejecting guinea-pig hearts. In human subjects studied at cardiac catheterisation, low-dose bicoronary infusions of sodium nitroprusside or of substance P induce similar effects on left ventricular systolic and diastolic function. These changes may benefit from cardiac filling and coronary perfusion by increasing the diastolic interval, reducing extravascular compressive forces and increasing the driving pressure for filling, e.g., during exercise. Nitric oxide may also modulate inotropic and chronotropic responses to beta-adrenergic stimulation. Under pathological conditions, overproduction of nitric oxide by an inducible nitric oxide synthase may be detrimental for contractile function. Dysfunction of the constitutive nitric oxide pathway could also contribute to pathophysiology, e.g., in conditions characterised by diastolic dysfunction. The paracrine nitric oxide pathway is likely to be an important regulator of cardiac contractile function, acting in concert and interacting with other regulatory pathways.
Int J Cardiol 1995 Jul
PMID:The influence of endothelium-derived nitric oxide on myocardial contractile function. 853 45

Nitric oxide (NO) is an endogenous protectant against reperfusion-induced ventricular fibrillation (VF) in the rat isolated heart. Here, the following were investigated: (1) the tissue source of cardioprotective NO using a novel inhibitor (7-nitro indazole; 7-NI) of the neuronal form of NO synthase (NOS) and direct detection of coronary effluent NO by chemiluminescence; and (2) the species dependence by comparing rat and rabbit hearts. Perfusion with modified Krebs solution was followed by 60 min left regional ischemia and 10 min reperfusion. 7-NI (1 microM) increased the incidence of VF from 0% to 60% in rat hearts (n = 10; P < 0.05). Co-perfusion with L-arginine (1 mM) reduced VF incidence to 20% (P:N.S. v controls). The inactive analog of 7-NI (6-amino indazole: 6-AI) had no pro-fibrillatory activity. Neither 7-NI nor 6-AI affected coronary flow or recovery of flow during reperfusion. 7-NI reduced basal coronary effluent NO levels to below the limit of detection (< 1 pmol), but a massive increase in NO levels occurred when L-arginine was co-perfused with 7-NI. Although 7-NI had no effect on basal coronary flow and, by implication, resting NO release, it was found, in separate studies, to antagonise substance P-induced vasodilatation and NO release, suggesting that its neuronal selectivity is lost in the presence of an exogenously administered activator of endothelial NOS in rat hearts. In rabbit hearts, in contrast, 7-NI had no effect on VF or NO levels. However, in rabbit hearts the isozyme non-selective NO synthase blocker, NG-nitro-L-arginine methyl ester (L-NAME; 100 microM), increased VF incidence from 0 to 50% (P < 0.05) and, during the first minute of reperfusion, reduced NO levels from 4929 +/- 893 to 2505 +/- 483 pmol/min/g (P < 0.05) and recovery of coronary flow by 22% (P < 0.05). Each of these effects were prevented by L-arginine co-perfusion. These data indicate a role for basally released NO as an endogenous antifibrillatory cardioprotectant in rat and rabbit isolated heart and indicate that the tissue source (neuronal in rat but not in rabbit heart) is species-dependent.
J Mol Cell Cardiol 1996 Oct
PMID:Endogenous protection against reperfusion-induced ventricular fibrillation: role of neuronal versus non-neuronal sources of nitric oxide and species dependence in the rat versus rabbit isolated heart. 893 Aug 5

Dietary Mg-deficiency increases the susceptibility of rat hearts to ischemia-reperfusion (I-R) injury in vitro, and also promotes substance P-associated neurogenic inflammation in vivo. The relationship between Mg-deficiency-induced neurogenic inflammation and the subsequently-enhanced free radical-mediated oxidative and functional injury during I-R was examined using the substance P receptor antagonist, L-703,606. Rats maintained on 3-week Mg-deficient (MgD; <1.8 mmol Mg/kg food) or Mg-sufficient (MgS; 25 mmol Mg/kg) diets were treated during this time with either L-703,606 (1.0 or 3.5 mg/sustained-release pellet, s.c.) or a placebo, prior to isolated perfused I-R. Post-ischemic functional recovery (pressure-volume work), myocardial effluent lactate dehydrogenase (LDH) activity, and lipid hydroperoxides (LOOH) were assessed after 30-min global ischemia. Lipid peroxidation-derived free radical production was monitored by alpha-phenyl-N-t-butylnitrone (PBN) spin trap infusion (2-3 mM final) and toluene-extracted effluents were analyzed by electron spin resonance (ESR) spectroscopy. PBN/alkoxyl adducts (alpha(H) = 1.89-1.93 G, alpha(N) = 13.58-13.63 G) were the dominant ESR signals detected in MgS and MgD I-R hearts; however, MgD hearts exhibited greater total LOOH (2.9 x higher) and alkoxyl adduct production (2.3 x higher), higher tissue LDH release (1.8 x ) and lower functional recovery (51% less) than MgS hearts. MgD rats treated with L-703,606 displayed a dose-dependent improvement in myocardial functional recovery (1.5-2 x higher), and reductions in LDH release (42-59% lower), total LOOH content (36-73% lower) and alkoxyl production (40-65% lower). Interestingly. L-703,606 treatment did not reduce functional impairment or lessen the tissue and oxidative injury experienced by MgS I-R hearts. These findings suggest that L-703,606 reduced oxidative injury and improved functional recovery of MgD I-R hearts by retarding substance P-mediated inflammatory/pro-oxidant events during the in vivo development of Mg-deficiency.
J Mol Cell Cardiol 1997 Jan
PMID:Magnesium-deficiency-enhanced post-ischemic myocardial injury is reduced by substance P receptor blockade. 904 25


<< Previous 1 2 3 Next >>