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)

A role for peptidergic nerves in the adult respiratory distress syndrome (ARDS) was examined by radioimmunochemically quantifying neuropeptides in pulmonary edema (PE) fluids from seven patients with ARDS and six patients with PE from congestive heart failure (CHF). The PE fluid mean concentrations of substance P (SP) and gastrin-releasing peptide (GRP) were significantly higher in ARDS (0.59 +/- 0.29 SD and 0.10 +/- 0.03 nM, respectively, P < 0.001 for both) than in CHF (0.19 +/- 0.08 and 0.04 +/- 0.01), whereas no difference was detected between the mean levels of vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) in the two forms of PE. Mean alveolar fluid concentration of SP was 8.7 nM (range 2.1-20.5 nM, N = 4) in sheep with acute lung injury from intravenous Pseudomonas aeruginosa, but was undetectable in sheep with balloon-induced high left atrial pressure simulating CHF (N = 2) or control sheep (N = 2). Pulmonary lymphatic clearance of SP, which reflected the rate of generation of SP in the lungs, attained a maximum of 25-95 pmol/h in sheep given P. aeruginosa intravenously, but was detected in only one of four control sheep at a lower level. Some pulmonary neuropeptides thus are released locally by acute lung injury and may contribute to endothelial and/or epithelial abnormalities underlying the altered capillary-alveolar permeability in ARDS.
 ...
PMID:Neuropeptides in pulmonary edema fluid of adult respiratory distress syndrome. 142 25

The effects of angiotensin-converting-enzyme (ACE) inhibitors on circulatory regulating mechanisms in congestive heart failure (CHF) were studied by comparison of plasma levels of catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), substance P (SP-LI), calcitonin gene-related peptide (CGRP-LI), vasopressin (ADH-LI), atrial natriuretic peptide (ANP-LI) and renin activity (PRA) in patients with severe CHF (NYHA III-IV) with (n = 15) or without (n = 17) ACE inhibitors in addition to digoxin and diuretic therapy. Data were also compared with those for healthy subjects (n = 31) and patients with moderate CHF (NYHA I-II). Catecholamines and NPY-LI were increased to the same extent in both groups with severe CHF. CGRP-LI showed no changes relative to controls in any of the patient groups, and was not affected by ACE inhibitors. The SP-LI level was significantly increased in all patient groups. Patients with severe CHF on ACE inhibition had a SP-LI level of 4.05 +/- 0.79 pmol l-1, compared to a concentration of 2.28 +/- 0.30 pmol l-1 (P less than 0.05) in the patient group with a comparable degree of CHF but without ACE inhibition. In the latter group, an inverse relationship appeared between the SP-LI and the serum sodium levels (r = -0.68, P less than 0.05). The patients with severe CHF who received ACE inhibitors had significantly lower ADH-LI levels than the patients with a comparable degree of CHF who were not treated with ACE inhibitors, while the ANP-LI levels was increased to a similar extent in both groups.
 ...
PMID:Increased plasma level of substance P in patients with severe congestive heart failure treated with ACE inhibitors. 171 29

In controls and in patients suffering from congestive heart failure (CHF) the circulating levels of catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), vasoactive intestinal peptide-LI (VIP-LI), substance P-LI (SP-LI) and calcitonin generated peptide-LI (CGRP-LI) markers of sympathetic, parasympathetic and sensory nervous systems, respectively, have been examined. There was a significant rise in the levels of noradrenaline, NPY-LI and SP-LI already in moderate CHF (New York Heart Association Stage I and II). In patients with severe CHF (NYHA Stage III and IV) the circulating levels of noradrenaline, adrenaline, NPY-LI and SP-LI were significantly increased. CGRP-LI was not altered, despite the fact that this peptide co-exists in many tissues with SP. There was no change in VIP-LI. The pathophysiological significance of this pattern of reaction of circulating catecholamines and neuropeptides is unclear; however, the rise in SP-LI may be a reaction to counterbalance the vasoconstrictive effects of the activation of the sympatho-adrenal system.
 ...
PMID:Congestive heart failure: involvement of perivascular peptides reflecting activity in sympathetic, parasympathetic and afferent fibres. 210 40

Angiotensin converting enzyme inhibitors (ACEI) are used widely in the treatment of both hypertension and congestive heart failure. Although usually well tolerated, these medications may produce side effects that may be encountered by the allergist, including cough, angioedema, and rhinitis symptoms. The severity of ACEI-induced cough may vary, and is associated with increased bronchial hyperreactivity in some (but not all) patients as judged by methacholine sensitivity. Angiotensin converting enzyme inhibitor-induced cough may have its onset from one day to 12 months after initiation of therapy, and is not dose dependent. Angioedema caused by ACEI is usually mild and clears with discontinuation of the drug, however cases requiring intubation and tracheostomy have been reported. The mechanism of ACEI-induced cough remains unclear, but could be in part due to accumulation of substances whose degradation may also be impeded by ACEI, such as substance P, bradykinins, and/or prostaglandins. Knowledge of the side effects produced by this class of medication may help patients avoid unnecessary, costly, and often invasive diagnostic evaluations.
 ...
PMID:Angiotensin converting enzyme inhibitors and the allergist. 222 91

It was examined to what extent congestive heart failure (CHF) in rats, induced by ligation of the left coronary artery, affects the vascular responses to the vasodilatory substances acetylcholine (ACh), calcitonin gene-related peptide (CGRP), and substance P (SP). After induction of CHF status, the basilar, mesenteric and renal arteries and the iliac vein were studied in vitro. Dilatory responses were determined in relation to pre-contraction by the thromboxane mimetic U46619. Sham-operated animals (Sham) served as controls. U46619 induced stronger contraction in CHF basilar and renal arteries compared with the corresponding segments in Sham. ACh induced concentration-dependent dilations in all vessels examined with no difference of maximum relaxation or potency between CHF and Sham. SP induced weak dilations in all arteries examined while the response was markedly attenuated in CHF iliac veins compared with Sham (Emax% 12.2 +/- 3.4 vs. 32.3 +/- 4.8, P = 0.01). The CGRP induced dilation in the CHF basilar artery was weaker (Emax% 18.6 +/- 6.5 vs. 66.9 +/- 5.0, P < 0.001) and less potent (pEC50: 8.2 +/- 0.2 vs. 9.0 +/- 0.2, P = 0.01) compared with Sham. Further, CGRP was less potent in the renal artery of CHF rats compared with Sham (pEC50: 8.1 +/- 0.2 vs. 9.5 +/- 0.3, P < 0.01). In the CHF iliac vein, CGRP was more potent compared with Sham (pEC50: 9.7 +/- 0.4 vs. 8.3 +/- 0.4, P < 0.05). It can be concluded CHF is accompanied by alterations in the vascular response to the dilatory substances studied. The changes differ between vascular beds and between the different substances.
 ...
PMID:Dilatory responses to acetylcholine, calcitonin gene-related peptide and substance P in the congestive heart failure rat. 1007 92

Activation of the renin-angiotensin-aldosterone system (RAAS) in left ventricular systolic dysfunction is a critically important determinant in the pathophysiologic processes that lead to progression of heart failure and sudden death. Angiotensin II, acting at the specific angiotensin receptor (AT1-R), activates a series of intracellular signaling sequences which are ultimately expressed within the cardiovascular system as vasoconstriction and associated vascular hypertrophy and remodeling. Angiotensin converting enzyme (ACE) inhibition leads to increases in the vasodilatory peptides bradykinin and substance P and at least an initial reduction in angiotensin II concentrations. AT1-R blocking drugs prevent access of angiotensin II to the AT1-R and thus prevent cellular activation. ACE inhibitors have clearly been demonstrated through a large number of clinical trials to increase survival in congestive heart failure, primarily by reducing the rate of progression of left ventricular dilatation and decompensation. However, this beneficial effect diminishes over time. Preliminary short-term clinical studies evaluating the efficacy of AT1-R blocking drugs in the treatment of heart failure have suggested that they elicit similar hemodynamic and neuroendocrine effects as do the ACE inhibitors. The combination ACE inhibitors and AT1-R blocking drugs offer the theoretical advantage of increasing bradykinin while blocking the actions of angiotensin II, and thus possibly show a synergistic effect. Again, preliminary studies have yielded encouraging results that are difficult to interpret because neither ACE inhibitor nor the AT1-R blocking drug doses were titrated to tolerance. Pharmacological manipulation of the RAAS has led to better understanding of its role in heart failure and improved clinical outcomes.
 ...
PMID:Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the treatment of heart failure caused by left ventricular systolic dysfunction. 1036 49

Coronary artery disease and congestive heart failure (CHF) have been associated with a reduction in nitric oxide (NO) release or bioavailability from the vascular endothelium. The objectives of this study were to compare the role of NO in human coronary vessels isolated from nonischemic dilated (DCM) (n = 10) and ischemic (ICM) (n = 12) cardiomyopathic hearts. Segments were mounted on a wire myograph to record changes in isometric tension. All experiments were performed in the presence of indomethacin (10 microM). Contractions induced by angiotensin II (0.1 microM) or a depolarizing physiologic solution containing 40 mM KCl, were of similar amplitude in DCM and ICM. In vessels precontracted with angiotensin II, acetylcholine (1 microM) caused an endothelium-dependent relaxation of rings from DCM but a paradoxical contraction of rings from ICM; NO synthase inhibition with Nomega-nitro-L-arginine (L-NNA, 100 microM) did not affect acetylcholine-induced relaxation or contraction of DCM or ICM vessels, respectively. By contrast, substance P (0.1 microM) induced an endothelium-dependent relaxation in both groups of vessels; this relaxation was prevented (p < 0.05) by L-NNA in vessels from ICM hearts but only reduced (p < 0.05) by L-NNA in vessels from DCM hearts. In depolarized conditions, acetylcholine contracted (p < 0.05) whereas substance P induced a complete relaxation (p < 0.05) of vessels from both groups: substance P-induced relaxation was abolished (p < 0.05) by L-NNA. Our data suggest that in the presence of indomethacin, NO does not contribute to acetylcholine-induced relaxation of human epicardial coronary arteries isolated from DCM hearts. Furthermore, whereas NO and a secondary endothelium-derived relaxing factor sensitive to high K+ contribute to substance P-induced relaxation of rings from DCM hearts, only NO is involved in ICM hearts.
 ...
PMID:Different contribution of endothelial nitric oxide in the relaxation of human coronary arteries of ischemic and dilated cardiomyopathic hearts. 1121 5

Imidapril hydrochloride (imidapril) is a long-acting, non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor, which has been used clinically in the treatment of hypertension, chronic congestive heart failure (CHF), acute myocardial infarction (AMI), and diabetic nephropathy. It has the unique advantage over other ACE inhibitors in causing a lower incidence of dry cough. After oral administration, imidapril is rapidly converted in the liver to its active metabolite imidaprilat. The plasma levels of imidaprilat gradually increase in proportion to the dose, and decline slowly. The time to reach the maximum plasma concentration (T(max)) is 2.0 h for imidapril and 9.3 h for imidaprilat. The elimination half-lives (t(1/2)) of imidapril and imidaprilat is 1.7 and 14.8 h, respectively. Imidapril and its metabolites are excreted chiefly in the urine. As an ACE inhibitor, imidaprilat is as potent as enalaprilat, an active metabolite of enalapril, and about twice as potent as captopril. In patients with hypertension, blood pressure was still decreased at 24 h after imidapril administration. The antihypertensive effect of imidapril was dose-dependent. The maximal reduction of blood pressure and plasma ACE was achieved with imidapril, 10 mg once daily, and the additional effect was not prominent with higher doses. When administered to patients with AMI, imidapril improved left ventricular ejection fraction and reduced plasma brain natriuretic peptide (BNP) levels. In patients with mild-to-moderate CHF [New York Heart Association (NYHA) functional class II-III], imidapril increased exercise time and physical working capacity and decreased plasma atrial natriuretic peptide (ANP) and BNP levels in a dose-related manner. In patients with diabetic nephropathy, imidapril decreased urinary albumin excretion. Interestingly, imidapril improved asymptomatic dysphagia in patients with a history of stroke. In the same patients it increased serum substance P levels, while the angiotensin II receptor antagonist losartan was ineffective. These studies indicate that imidapril is a versatile ACE inhibitor. In addition to its effectiveness in the treatment of hypertension, CHF, and AMI, imidapril has beneficial effects in the treatment of diabetic nephropathy and asymptomatic dysphagia. Good tissue penetration and inhibition of tissue ACE by imidapril contributes to its effectiveness in preventing cardiovascular complications of hypertension. The major advantages of imidapril are its activity in the treatment of various cardiovascular diseases and lower incidence of cough compared with some of the older ACE inhibitors.
 ...
PMID:Protection of the cardiovascular system by imidapril, a versatile angiotensin-converting enzyme inhibitor. 1217 88

Increasing renal pelvic pressure results in PGE(2)-mediated release of substance P. Substance P increases afferent renal nerve activity (ARNA), which leads to a reflex increase in urinary sodium excretion (U(Na)V). Endogenous ANG II modulates the responsiveness of renal mechanosensory nerves. The ARNA and U(Na)V responses are suppressed by low- and enhanced by high-sodium diet. We examined whether the ARNA responses are altered in rats with congestive heart failure (CHF), a condition characterized by increased ANG II and sodium retention. The ARNA responses to increasing renal pelvic pressure </=7.5 mmHg were suppressed in CHF vs. sham-CHF rats fed normal sodium diet. In CHF rats, increasing renal pelvic pressure 2.5 and 7.5 mmHg increased ARNA 0 +/- 1 and 13 +/- 2% (P < 0.01) before and 9 +/- 1 (P < 0.01) and 19 +/- 1% (P < 0.01) during renal pelvic perfusion with losartan. Losartan had no effect on the ARNA responses in sham-CHF rats. In isolated renal pelvises from CHF rats, PGE(2) increased substance P release from 11 +/- 2 to 15 +/- 3 pg/min (not significant) without and from 16 +/- 2 to 30 +/- 4 pg/min (P < 0.01) with losartan in the incubation bath. Losartan had no effect on PGE(2)-mediated substance P release in sham-CHF rats. In conclusion, the responsiveness of renal mechanosensory nerves is impaired in CHF rats due to ANG II inhibiting PGE(2)-mediated release of substance P from renal pelvic nerves.
 ...
PMID:Impaired responsiveness of renal mechanosensory nerves in heart failure: role of endogenous angiotensin. 1238 53

Pretreatment of anaesthetized guinea-pigs with either CHF 4226.01 (8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(p-methoxyphenyl)-1-methylethyl]amino]ethyl] carbostyril hydrochloride), formoterol or budesonide reduced acetaldehyde (AcCHO)-evoked responses in the lungs with a rank order of potency CHF 4226.01 (ED(50) values, from 1.88 to 3.31 pmol) > formoterol (ED(50) values, from 3.03 to 5.51 pmol) >> budesonide (ED(50) values, from 335 to 458 nmol). The duration of action of CHF 4226.01 in antagonizing the airway obstruction elicited by AcCHO was also substantially longer than formoterol (area under the curve) at 10 pmol, 763+/-58 and 480+/-34, respectively; P<0.01). Continuous infusion of a subthreshold dose of AcCHO enhanced the intratracheal pressure (ITP) increases caused by subsequent challenges with substance P (from 9.7+/-0.8 to 27.5+/-1.6 cm H(2)O as a peak, P<0.001). Pretreatment with either CHF 4226.01 or formoterol prevented the sensitizing effect of AcCHO on substance P responses (ED(50) values, 2.85 and 6.11 pmol, respectively; P<0.01). The ED(50) value of budesonide (396 nmol) in preventing AcCHO-evoked ITP increase was reduced when this glucocorticoid was combined with 0.1 pmol CHF 4226.01 (ED(50) 76 nmol; P<0.001). CHF 4226.01/budesonide was two-fold more effective (P<0.01) than the formoterol/budesonide combination. These results suggest that CHF 4226.01/budesonide, by optimizing each other's beneficial potential in the control of pulmonary changes caused by AcCHO in the guinea-pigs, may represent a new fixed combination in asthma.
 ...
PMID:Positive interaction of the beta2-agonist CHF 4226.01 with budesonide in the control of bronchoconstriction induced by acetaldehyde in the guinea-pigs. 1565 2


1 2 Next >>