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)

Isolated precontracted arteries of various vascular beds relax in response to acetylcholine only if the endothelium is present. One explanation for this is that this drug stimulates the endothelial cells to release a vasodilator substance that in turn relaxes the underlying smooth muscle. To determine whether this mechanism is concerned also in the acetylcholine contraction of isolated porcine coronary arteries transverse strips of the extramural part of the left circumflex artery were used for recording isometric tension in the muscle bath. Dose-response curves for acetylcholine showed no significant difference before and after removal of endothelium. As a functional check on the removal of endothelium, the responsiveness of each preparation to a known endothelium dependent dilator (substance P) was tested before and after removal. These findings suggest that endothelial cells are not concerned in the acetylcholine induced contraction of porcine coronary arteries. Acetylcholine appears to act directly on smooth muscle of the porcine artery.
Cardiovasc Res 1986 Apr
PMID:Absence of role of endothelium in the response of isolated porcine coronary arteries to acetylcholine. 371 11

Three preparations of the rat hepatic portal vein, everted, noneverted, and longitudinal strip, were examined for their responsiveness to noradrenaline (NA), substance P (SP), and eledoisin (ED). The longitudinal strips and the everted veins exhibited similar sensitivities to these compounds, whereas the noneverted vein was two to four times less sensitive. The time course to generation of a maximal response was markedly slower for the noneverted vein. The poor reactivity of the noneverted vein is attributed to a reduced accessibility of the compounds to receptor sites. The myogenic responses of the longitudinal strips to NA and ED but not SP were characterized by a tonic-type contracture, whereas everted and noneverted preparations responded to the peptides, at low and intermediate concentrations, with large-amplitude and long-duration contractions. The everted vein is presented as a useful preparation for evaluation of drug-receptor interactions.
J Cardiovasc Pharmacol
PMID:Everted portal vein: a sensitive model for studies of vasoactive compounds. 618 67

A brief review is first presented of findings during the past few years by the authors and by others on the nonprostaglandin endothelium-dependent relaxation of isolated arteries by a large number of vasoactive agents. Among these agents are acetylcholine (ACh); the calcium ionophore A23187; ATP and ADP; substance P; bradykinin (canine, human, and porcine arteries); histamine, acting via an H1-receptor (rat arteries); thrombin (canine arteries); serotonin (canine coronary artery); and norepinephrine, acting via an alpha2-receptor (canine coronary artery). The endothelium-derived relaxing factor (EDRF) released by ACh and other agents has not yet been identified. Our original hypothesis that arachidonic acid is the precursor of EDRF is not supported by the finding that other unsaturated fatty acids in addition to arachidonic acid, and even stearic acid, elicited nonprostaglandin endothelium-dependent relaxations. Methylene blue and hemoglobin (but not methemoglobin) rapidly inhibited relaxation of rabbit aorta by ACh or A23187, suggesting that our proposal that EDRF is a labile free radical may be correct. The endothelium-dependent relaxation by each of these agents was shown to be preceded by an endothelium-dependent increase in cyclic GMP in the smooth muscle--a finding consistent with the hypothesis that EDRF stimulates guanylate cyclase in the muscle, leading to an increase in cyclic GMP that somehow activates relaxation. Some questions relating to the potential physiological important of endothelium-dependent relaxations are discussed.
J Cardiovasc Pharmacol 1984
PMID:Endothelial cells as mediators of vasodilation of arteries. 620 42

It is presumed that the contractile tone of precapillary blood vessels is regulated by various mechanisms. Disseminated endocrine cells are sites of production of vasoactive peptides, which are partly involved in the regulation of the local or systemic circulation. The peptide hormones may exert a direct effect on smooth-muscle cells, but the action may also be mediated by the stimulation of perivascular mast cells, perivascular nerves, or endothelial cells. Among these vasoactive peptides, attention is focused on neurotensin, substance P, and vasoactive intestinal polypeptide.
J Cardiovasc Pharmacol 1984
PMID:Morphofunctional anatomy of disseminated endocrine cells related to the regulation of precapillary vessels. 620 44

The response of G-protein-coupled receptors is modulated by homologous desensitization. Because endothelin A receptor (ETA) plays a part in vasoconstriction, the extent of desensitization and resensitization of endothelin responsiveness was studied. A cDNA clone encoding human ETA receptor was isolated based on similarities to bovine endothelin A receptor. Xenopus laevis oocytes injected with cloned mRNA transcripts were used as a model system for analyzing desensitization. Human neurokinin A (NKA) receptor was used for comparison with ETA receptor in desensitization experiments. Xenopus laevis oocytes injected with the two receptor mRNAs show homologous desensitization but variable rates of recovery. Human NKA receptors desensitize within 5 min and resensitize after 20-30 min. Human ETA receptors also desensitize within 5 min but have a prolonged resensitization period lasting 1.5-2 h. Such a prolonged recovery period is unique to this class of receptors and may serve to regulate some of the deleterious effects mediated by the ETA receptor. The mechanism of differential desensitization is being investigated using genetically engineered mutants of human ETA receptor.
J Cardiovasc Pharmacol 1993
PMID:Desensitization of human endothelin A receptor. 750 17

We investigated the role of nitric oxide (NO) in the mediation of nerve stimulation-induced vasodilation in skeletal muscle. Hindlimb blood flow and vascular resistance were measured in pentobarbital-anesthetized, paralyzed, and guanethidine-treated rabbits. Centrifugal electrical stimulation of the sciatic nerve bundle induced reproducible, frequency-, voltage-, and pulse duration-dependent decrements in vascular resistance. The tachykinin antagonist CP-96,345 (1 mg/kg intravenously, i.v.) attenuated the vasodilation induced by intraarterially (i.a.) administered substance P but not by adenosine. Furthermore, CP-96,345 attenuated the decrease in vascular resistance in response to nerve stimulation, from 22.9 +/- 3.2 to 4.5 +/- 4.1% of control resting resistance (p < 0.005), without affecting basal vascular resistance. An inhibitor of NO formation, N omega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg i.v.), increased vascular resistance from 6.1 +/- 0.5 to 9.1 +/- 1.2 resistance units (p < 0.05) and significantly attenuated the vascular response to i.a. administered substance P but not adenosine. Finally, nerve stimulation-induced reduction in vascular resistance was attenuated by L-NAME, from 22.6 +/- 2.7 to 7.0 +/- 1.0% of control (p < 0.001). These findings suggest that tachykinins and NO are involved in mediation of vasodilation in response to the present type of nerve stimulation. The data are consistent with the hypothesis that NO is produced subsequent to neural release of tachykinin-type transmitter(s).
J Cardiovasc Pharmacol 1994 Apr
PMID:Neurogenic vasodilation in rabbit hindlimb mediated by tachykinins and nitric oxide. 751 11

Experiments were designed to study the effects of trandolaprilat on endothelium-dependent responses in isolated blood vessels. Rings of either femoral or left circumflex coronary arteries of the dog or thoracic aortas of normotensive rats were suspended in organ chambers for isometric tension recording. During contractions induced by prostaglandin F2 alpha, trandolaprilat did not cause direct endothelium-dependent or -independent relaxation. However, when given to preparations incubated with angiotensin I or bradykinin, the compound evoked significant endothelium-dependent relaxation. By contrast, trandolaprilat failed to cause any change in tension when given in the presence of acetylcholine (ACh). In rings of femoral arteries, trandolaprilat potentiated the endothelium-dependent relaxation evoked by bradykinin and adenosine diphosphate; it did not modify the endothelium-dependent relaxations induced by ACh, substance P, or thrombin. In rings of femoral arteries without endothelium, trandolaprilat augmented relaxation induced by adenosine diphosphate (ADP) but not by adenosine. In perfused coronary arteries with but not those without endothelium, trandolaprilat caused relaxation in the absence of exogenous bradykinin (or ADP). These experiments suggest that trandolaprilat does not directly release endothelium-derived relaxing factor from the endothelial cells, does not interfere with the ability of the endothelium to release endothelium-derived relaxing factor, augments the endothelium-dependent responses to bradykinin (given exogenously or produced locally) and angiotensin I by direct interaction with converting enzyme, and potentiates the relaxation induced by ADP by augmenting its direct effect on vascular smooth muscle.
J Cardiovasc Pharmacol 1994
PMID:The endothelium and vascular effects of the ACE inhibitor trandolaprilat. 752 94

We investigated the action of oral naftidrofuryl, a serotonin (5-HT2)antagonist, on atheromatous plaque formation, endothelial function, and neutrophil activity in cholesterol-fed (1% for 12 weeks) rabbits. Cholesterol feeding caused almost complete (84 +/- 4%) coverage of the aortic surface with atheromas and a marked intimal thickening. The endothelium-dependent relaxation to acetylcholine (ACh 1 nM-10 microM) and substance P (30 nM) was considerably reduced, whereas the relaxing effect to the endothelium-independent nitric oxide donor linsidomine (SIN-1) (100 microM) was unchanged. Treatment of hypercholesterolemic rabbits with naftidrofuryl (50 mg/kg body weight) resulted in a marked (54 +/- 6%, p < 0.05) reduction in aortic plaque formation. Endothelium-dependent relaxation to ACh was significantly improved in rings of both thoracic aorta: 33 +/- 5 versus 14 +/- 5% (p < 0.05) and abdominal aorta 68 +/- 9 versus 37 +/- 10% (p < 0.05). Similar results were obtained with substance P, but the responses to SIN-1 were unchanged. Zymosan-induced, luminol-enhanced chemiluminescence of polymorphonuclear leukocytes (PMN) was markedly stimulated in cholesterol-fed rabbits. Naftidrofuryl reduced this hyperreactivity to that of control rabbits. There was no change by naftidrofuryl in any of these parameters in control rabbits, precluding a direct action of the compound in nonhypercholesterolemic conditions. These data demonstrate significant endothelium-protective actions of long-term oral naftidrofuryl in cholesterol-fed rabbits that involve inhibition of cholesterol-induced neutrophil activation.
J Cardiovasc Pharmacol 1995 May
PMID:Antiatherosclerotic effects of oral naftidrofuryl in cholesterol-fed rabbits involve inhibition of neutrophil function. 754 72

The internal mammary artery has greater long-term patency than the saphenous vein when used for coronary bypass grafting. Therefore, bilateral use of the internal mammary artery for grafting with the right internal mammary artery used as a "free" graft may result in improved graft survival. The study objectives were to compare the endothelial-dependent and -independent vasodilatory response in free and pedicled internal mammary artery grafts in patients who had previously undergone coronary surgery. Free (group 1, n = 8) and pedicled (group 2, n = 7) internal mammary artery grafts were studied by comparing the response to selective infusion of the endothelial-dependent vasodilator substance P (1.4 up to 22.4 pmol/min in doubling dose increments) followed by isosorbide dinitrate (2 mg over 2 minutes), in patients undergoing coronary angiography, 1 month to 6 years after coronary surgery. Maximal dilatory response to substance P was 8.7% +/- 1.8% in pedicled grafts compared with 8.8% +/- 2.3% in free grafts (p = not significant), with the dose response for both groups being similar. Infusion of isosorbide dinitrate produced only minimal further dilatation in both groups. No significant difference was found in endothelium-dependent and -independent vasodilatory response between free and pedicled internal mammary artery grafts, suggesting that the use of the free right internal mammary artery and other arterial grafts may enhance graft survival.
J Thorac Cardiovasc Surg 1995 Aug
PMID:Late endothelial function of free and pedicled internal mammary artery grafts. 858 28

In isolated porcine coronary arteries, acetylcholine elicited contractions that were potentiated by endothelium denudation. In endothelium-intact strips, the contraction deteriorated by repeated trials and was reversed to a relaxation. NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthesis inhibitor, abolished the relaxation or reversed it to a contraction. Endothelium-dependent relaxations caused by serotonin were also reversed to a contraction by treatment with L-NA. Relaxations caused by substance P were dependent on the endothelium and were abolished by oxyhemoglobin; however, L-NA did not completely abolish the relaxation. It may be concluded that porcine coronary arteries respond to acetylcholine with contractions by a direct action on smooth muscle that are minimized by stimulated release of NO from the endothelium. It appears that the relaxation caused by serotonin is due to NO released from the endothelium, whereas the substance P-induced relaxation is associated mainly with endothelium-derived NO produced by NO synthase sensitive to L-NA and also with NO produced via a L-NA-resistant process or via a pathway distinct from that through NO synthase.
J Cardiovasc Pharmacol 1993 Feb
PMID:Mechanisms of endothelium-dependent responses to vasoactive agents in isolated porcine coronary arteries. 767 56


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