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)

Endothelium-dependent relaxations in response to substance P and bradykinin were lower in atherosclerotic than in normal human coronary arteries. The relaxation induced by substance P was inhibited by L-NG-monomethylarginine (L-NMMA), which shows that release of nitric oxide is involved in the mediation of endothelium-dependent relaxation in these arteries. L-NMMA also inhibited a basal component of endothelium-dependent relaxation. The basal secretion of nitric oxide was significantly lower in diseased than in normal arteries. These findings suggest that atherosclerotic human coronary arteries lack an important protective mechanism that normally guards against vasospasm and thrombosis.
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PMID:Low basal and stimulated release of nitric oxide in atherosclerotic epicardial coronary arteries. 197 93

Relaxant responses to transmural electrical stimulation and nicotine of cerebral artery strips obtained from dogs and Japanese monkeys were abolished by tetrodotoxin and hexamethonium, respectively, and suppressed by treatment with NG-monomethyl-L-arginine (L-NMMA), a nitric oxide (NO) synthesis inhibitor. The inhibitory effect was prevented and reversed by L-arginine but not by D-arginine. The relaxations suppressed by L-NMMA were not increased by exogenously applied NO. Endothelium denudation did not alter the response to transmural stimulation and nicotine or the inhibitory effect of L-NMMA. D-NMMA did not inhibit the response to vasodilator nerve stimulation. Dog coronary artery relaxations caused by transmural stimulation were not inhibited by L-NMMA but reversed to contractions by propranolol. Relaxations caused by substance P of dog cerebral arteries treated with indomethacin were dependent on endothelium and inhibited by L-NMMA, whereas those by NO and nitroglycerin, endothelium-independent relaxations, were unaffected. It is concluded that chemical and electrical stimulation of vasodilator nerves relaxes dog and monkey cerebral arteries, possibly by a mediation of NO rather than a stimulating action of NO on the release of vasodilator transmitter. Endothelium-dependent relaxations by substance P of dog cerebral arteries appear to be mediated by NO.
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PMID:Mechanism underlying the response to vasodilator nerve stimulation in isolated dog and monkey cerebral arteries. 170 Jun 32

NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, markedly enhanced tonic ("hump") responses to transmural stimulation in guinea pig ileum longitudinal muscle. The enhancement of the hump responses was probably due to a prejunctional effect on substance P-like neurotransmission, since the action of L-NMMA was exerted also in the presence of atropine, and since responses to substance P, a mimic of nerve stimulation, were unaffected by L-NMMA as were cholinergic twitch responses and the overflow of [3H]choline. Further in support, the hump responses were blocked by the substance P antagonist Spantide. All effects of L-NMMA were stereospecifically reversed by L-arginine. Endogenous nitric oxide thus selectively modulates peptidergic neurotransmission in the gut.
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PMID:Modulation of autonomic neuroeffector transmission by nitric oxide in guinea pig ileum. 170 30

Nitric oxide (NO) or related nitroso compounds are an endothelium-derived relaxing factor (EDRF), originating from metabolism of L-arginine, L-Arginine analogues with chemically altered guanidino moity are potent and specific inhibitors of EDRF(NO) release. We evaluated effects of two L-arginine analogues, NG-monomethyl-L-arginine (L-NMMA, 100 microM) and N omega-nitro-L-arginine (L-NARG, 30 microM), on acetylcholine-, substance P-, and nitroglycerin-induced relaxation in the blood-perfused rabbit hindlimb in vivo and femoral arteries in vitro. L-NMMA and L-NARG selectively inhibited the vasodilator response to acetylcholine in rabbit femoral arteries in vitro, whereas endothelium-independent response to nitroprusside increased. L-NMMA (1.6 mg/min ia) in the blood-perfused rabbit hindlimb in vivo increased vascular resistance in the hindlimb by 23 +/- 3% (means +/- SE; n = 10) but did not inhibit the vasodilator responses to acetylcholine or substance P. L-NARG (10 mg/kg iv) increased systemic blood pressure by 26 +/- 3% (n = 7) and vascular hindlimb resistance by 22 +/- 9% (n = 8), and blood flow to hindlimb musculature, measured with microspheres, decreased by 46 +/- 5% (n = 6). Pretreatment with L-NARG, however, did not impair vasodilator responses to acetylcholine and substance P. These findings are consistent with the view that basal tone in resistance vessels in the rabbit hindlimb may be mediated by nitroso compounds, whereas agonist-stimulated vasodilation may be mediated by other mechanisms that do not involve the NO-synthesizing enzyme.
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PMID:Acetylcholine-induced vasodilatation in rabbit hindlimb in vivo is not inhibited by analogues of L-arginine. 170 95

We have examined the ability of the endothelium of human epicardial coronary arteries to secrete vasorelaxant substances in response to pharmacological stimulation and under basal conditions. In addition, we have attempted to characterise the chemical identity and biochemical pathway for the synthesis of endothelial derived relaxing factor. Human epicardial coronary arteries were removed from patients who were undergoing heart transplantation for reasons other than ischaemic heart disease. Arteries were cut into segments and suspended in 5 ml organ baths containing a modified Tyrodes solution at 37 degrees C, and gassed with a mixture of 95% oxygen and 5% carbon dioxide. Substance P (10(-10) - 10(-7) M) elicited a dose-dependent relaxation of the coronary segments but this action of substance P was dependent upon an intact endothelium. The maximum response of substance P was equivalent to 89 +/- 8.5% of the maximum effect induced by 1 microgram/ml glyceryl trinitrate. This vasorelaxant effect of substance P was unaffected by the presence of 10(-6) M indomethacin. L-NG-monomethyl-arginine (10(-4) M), a specific inhibitor of formation of nitric oxide from L-arginine, antagonised the relaxations induced by substance P, decreasing the maximum response of substance P to 34 +/- 10.5% of the response to glyceryl trinitrate. Upon application, L-NG-monomethyl-arginine caused a further 23.1 +/- 3.0 increase in tension on preconstricted vessels. This increase in tension was reversed with the addition of L-arginine, but was unaffected by D-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of nitric oxide in mediating endothelium dependent relaxations in the human epicardial coronary artery. 170 57

A diet containing 0.3% cholesterol was given to male New Zealand rabbits for 16 weeks; this produced atherosclerotic lesions (fatty streaks) on 80% of the intimal surface of the thoracic aorta and on 45% of the intimal surface of the abdominal aorta. The endothelium-dependent relaxations induced by acetylcholine, substance P and ionophore A23187 were inhibited in the atherosclerotic aortas. Besides the endothelium-independent relaxations induced by nitroglycerine, the relaxations induced by atrial natriuretic peptide (ANF) were also significantly reduced in the more atherosclerotic thoracic aorta. In bioassay experiments it was found that acetylcholine and substance P caused a smaller release of endothelium-derived relaxing factor (EDRF) from atherosclerotic thoracic aortas than from control thoracic aortas: the EDRF released by the vasodilators evoked less relaxation in atherosclerotic detector abdominal aortas than in control detector abdominal aortas. Nitric oxide evoked significantly less transient relaxation in the atherosclerotic thoracic and abdominal aortas than in the respective control tissues. The data indicate that as experimental atherosclerosis in the rabbit progresses, both vascular activity and EDRF release become affected; this leads to a complete loss of endothelium-dependent relaxation in the more atherosclerotic blood vessels.
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PMID:Release and vascular activity of endothelium-derived relaxing factor in atherosclerotic rabbit aorta. 170 15

The possibility that nitric oxide (NO) could have a role in the modulation of inflammatory oedema formation was investigated in rat skin using selective inhibitors of NO synthesis. Intradermally injected substance P (0.03-1 nmol) induced oedema which was inhibited by concurrent administration of the inhibitor of NO synthesis L-NG-nitro arginine methyl ester (L-NAME), but not by the enantiomer D-NAME. L-Arginine reversed the inhibitory effect of L-NAME. A second inhibitor of NO formation, L-NG-monomethyl arginine (L-NMMA), had a similar inhibitory effect on substance P-induced oedema. The results suggest that endogenous NO has a modulatory role in oedema formation induced by mediators of increased microvascular permeability.
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PMID:Evidence that endogenous nitric oxide modulates oedema formation induced by substance P. 170 19

The human gastroepiploic artery has been used as a coronary artery bypass conduit in a limited number of clinical studies. It has been postulated that the capacity of the endothelium to release vasoactive substances may contribute to differing patency rates observed in established bypass grafts. We have now examined endothelial function in the human gastroepiploic artery. Endothelium-dependent relaxations to substance P were observed. A maximum relaxation of 83.25% +/- 8.2% (mean +/- standard error) was attenuated to 48.5% +/- 16.4% in the presence of L-NG-monomethyl-arginine, a specific inhibitor of endogenous nitric oxide synthesis. Removal of the endothelium abolished the relaxations. With a specific radioimmunoassay, concomitant changes in levels of cyclic guanosine 3',5'-monophosphate, the second messenger that elicits smooth muscle relaxation after release of the endothelium-derived relaxing factor, were measured. It was found that the gastroepiploic artery had significantly higher resting and stimulated levels of cyclic guanosine 3',5'-monophosphate than either the internal mammary artery or the saphenous vein. In the presence of the cyclooxygenase inhibitor indomethacin, and indomethacin plus L-NG-monomethylanginine, the maximum relaxation was decreased to 70% +/- 9.5% and 59% +/- 10.8%, respectively. Our data demonstrate that endothelium-derived relaxing factor and prostacyclin may exhibit synergy in the control of vascular tone in this vessel. It is concluded that the endothelium of the gastroepiploic artery has a strong capacity to secrete vasodilators and inhibitors of platelet activity. This could have important influence on long-term patency.
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PMID:Endothelial function of human gastroepiploic artery. Implications for its use as a bypass graft. 836 Dec 5

This study determines the release of nitric oxide (NO) from the coronary circulation of Langendorff hearts of rabbits, subsequent to administration of glyceryl trinitrate (GTN) and SIN-1. NO was measured on-line in the coronary effluent by the oxyhaemoglobin technique. Infusion of either GTN (10-40 mumoles/l) or SIN-1 (0.1-2.3 mumoles/l) into the coronary inflow resulted in a concentration-dependent NO release into the coronary effluent and a decrease in the coronary vascular resistance. NO generation from SIN-1 was identical with and without passage of the coronary circulation whereas NO generation from GTN was only detected after passage of the coronary vascular bed. NO generation by both substances was in the same range as endogenous NO release by two endothelium-dependent vasodilators, bradykinin (0.05 mumoles/l) and substance P (0.05 mumoles/l). Oxyhaemoglobin used for the assay of NO, inhibited the relaxation by SIN-1, but did not reduce vessel relaxations induced by GTN or iloprost, a stable prostacyclin analogue. Removal of the coronary endothelium by trypsin or pretreatment with L-NG-Monomethylarginine (30 mumoles/l) did neither affect NO release from GTN and SIN-1 nor the vasodilatory effect of both substances. These data are the first to directly demonstrate endothelium-independent NO release from organic nitrates during passage of an intact organ circulation. They additionally suggest a subendothelial site of metabolic NO formation from GTN.
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PMID:On-line measurement of nitric oxide release from organic nitrates in the intact coronary circulation. 171 35

Nerve-induced vasodilatation was studied by intravital microscopy of the rabbit tenuissimus muscle, pretreated with pancuronium, phentolamine, and guanethidine. Nerve stimulation of the tenuissimus nerve induced a vasodilatation which was frequency and pulse duration-dependent and insensitive to atropine and propanolol but abolished by tetrodotoxin. The nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM), but not its enantiomer, D-NAME, markedly inhibited the vasodilation induced by nerve stimulation or by exogenous substance P or neurokinin A. Vasodilatation due to calcitonin gene-related peptide, prostaglandin E2 or nitroprusside was unaffected. The substance P antagonist, spantide (30 microM), significantly attenuated nerve-induced vasodilatation, in parallel with L-NAME. Our results indicate that nerve-induced vasodilatation in skeletal muscle can be attributed to the release of substance P and/or other tachykinins and that nitric oxide subsequently mediates the response to endogenous tachykinins released from nerves.
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PMID:Nerve-induced tachykinin-mediated vasodilation in skeletal muscle is dependent on nitric oxide formation. 172 18


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