UMLS:C0406810 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The role of endogenous bradykinin in mean arterial blood pressure (BP) homeostasis was studied in spontaneously hypertensive (SHR) and normotensive (WKY) rats by the use of a bradykinin B2-receptor antagonist (BKant; Hoe 140, 11.6 micrograms kg-1) and converting enzyme (kininase II) inhibitor (captopril, 10 mg). To obtain a response to captopril that was induced through inhibition of kinin-degradation only and not through inhibition of angiotensin II-formation, the studies were performed on binephrectomized male rats to eliminate the renin-angiotensin system. 2. The role of the nitric oxide (NO) and the adrenergic systems were evaluated by the use of NO-synthase inhibitor (L-NAME, 0.3 g kg-1) and phentolamine (2 mg kg-1), respectively. 3. The rats were anaesthetized and pretreated with two injections of vehicle (PBS) or drugs spaced 5 min apart: PBS + PBS; BKant + PBS; PBS + L-NAME; BKant + L-NAME; or phentolamine + L-NAME. All rats were given captopril 15 min later. Time-control groups were treated with L-NAME but not captopril. 4. In WKY rats, captopril did not significantly alter BP in any of the groups. In the SHR-PBS + PBS group, on the other hand, captopril induced an immediate fall in BP (delta BP = -23 +/- 4 mmHg, P < 0.0017) which was completely blocked by BKant (delta BP = 2 +/- 2 mmHg) (P < 0.0011). L-NAME did not significantly alter the immediate hypotensive response to captopril but disclosed a later hypertensive reaction. In L-NAME + BKant-treated rats, both the hypotensive response and the late hypertension was abolished. In rats treated with phentolamine + L-NAME, the immediate fall in BP was not different from the controls whereas the late hypertension was absent. 5. BKant itself had no effect on basal BP in either WKY or SHR even when a 10 times higher dose was tested in a separate set of experiments. This was true also for conscious, nonnephrectomized SHR rats. 6. It was concluded that endogenous production of bradykinin was demonstrable through kininase II-inhibition in hypertensive but not in normotensive rats. However, this endogenous bradykinin did not play a role in basal BP homeostasis. The captopril-induced hypotension depended on kinin but, under the present conditions, not on NO as a mediator. The fall in BP induced a compensatory adrenergic hypertensive response which was revealed when the continuous NO-synthesis was blocked by L-NAME.
...
PMID:The role of endogenous bradykinin in blood pressure homeostasis in spontaneously hypertensive rats. 886 25

Ketotifen is a tricyclic drug with a wide spectrum of pharmacological effects. We studied the actions of ketotifen on the mechanical activity of isolated segments of guinea-pig ileum, guinea-pig colon and mouse colon. In the guinea-pig ileum ketotifen induced small contractions and inhibited the contractions induced by carbachol and by electric field stimulation. Responses to bradykinin (in the absence or in the presence of atropine 1 microM) were similarly inhibited by ketotifen, with an IC50 of 23 microM. In the guinea-pig colon ketotifen evoked non-cholinergic contractions with a pD2 of 4.5, but still it inhibited responses to bradykinin (IC50 = 75 microM). Ketotifen relaxed the unstimulated mouse colon with a pD2 of 4.2. This effect persisted in the presence of propranolol and phentolamine (each 10 microM). Incubation of the mouse colon with the nitric oxide synthase inhibitors NG-nitro-L-Arginine methyl ester hydrochloride (L-NAME), or L-NG-nitro-arginine (L-NNA) (100-500 microM) did not alter the inhibitory action of ketotifen. The histamine H1 receptor antagonist chlorpheniramine (5 microM) or the nerve blocker tetrodotoxin (1 microM) did not alter the inhibitory effects of ketotifen. It is concluded that the actions of ketotifen are mediated by a non-cholinergic, non-histaminergic mechanisms.
...
PMID:The actions of ketotifen on intestinal smooth muscles. 887 38

The effect of chronic N omega-nitro-L-arginine methyl ester (L-NAME) treatment on the in vivo eosinophil migration induced by bradykinin, platelet-activating factor (PAF), lipopolysaccharide and carrageenin has been investigated in the rat using the pleurisy model. The in vitro (microchemotaxis chamber) eosinophil migration induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP), PAF and zymosan-activated serum was also evaluated in the rat. The eosinophils were obtained from the peritoneal cavity of male Wistar rats and isolated on a discontinuous metrizamide gradient. Chronic inhibition of nitric oxide biosynthesis was achieved by adding L-NAME to the drinking water to give an intake of approximately 75 mumol/rat/day for 4 weeks. Rats treated chronically with L-NAME developed a significant level of hypertension (163 +/- 4.8 mmHg; P < 0.01) compared with animals which received either the same dose of the inactive enantiomer D-NAME (124 +/- 3.2 mmHg) or tap water alone (119 +/- 1.6 mmHg). The intrapleural injection of bradykinin (50 micrograms), PAF (1 microgram), lipopolysaccharide (0.25 microgram) and carrageenin (125 micrograms) into untreated rats in vivo induced a significant level of eosinophil migration by 24 h post-injection. This migration was markedly reduced in L-NAME-treated rats. Eosinophils obtained from untreated rats showed a significant level of migration in vitro in response to fMLP (5 X 10(-8) M), PAF (10(-8) M) and zymosan-activated serum (27 microliters). In contrast, the migration induced by these chemotactic agents was markedly reduced in cells isolated from animals treated chronically with L-NAME. L-Arginine (5.5 mM), but not D-arginine (5.5 mM), restored the ability of eosinophils from L-NAME-treated animals to migrate in response to fMLP. Our results indicate that nitric oxide plays a major role in the in vivo and ex vivo migration of eosinophils.
...
PMID:Inhibition of eosinophil chemotaxis by chronic blockade of nitric oxide biosynthesis. 888 18

We compared the effects of acetylcholine (Ach) in intrapulmonary arteries and veins of adult sheep. Preconstricted arterial rings with endothelium relaxed with Ach whereas arteries without endothelium or pretreated with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, did not dilate. Venous rings with or without endothelium, whether under resting tension or preconstricted, always contracted with Ach. However, preconstricted veins dilated with bradykinin, another endothelium-dependent vasodilator. Preconstricted veins pretreated with indomethacin or SQ29548, a prostaglandin H2 (PGH2)/TxA2 receptor blocker, did not constrict but rather dilated with Ach. This dilation was abolished with removal of endothelium or treatment with L-NAME, indicating that endothelium-derived NO (EDNO) was mediating the dilation. We conclude that Ach is an endothelium-dependent vasodilator in ovine intrapulmonary arteries, whereas in veins, Ach elicits two responses: EDNO-mediated vasodilation and vasoconstriction mediated by TxA2/PGH2.
...
PMID:Differential responses of ovine intrapulmonary arteries and veins to acetylcholine. 889 65

The presence of parathyroid hormone-related protein (PTHrP) in human kidney vasculature and the signal transduction pathways stimulated during PTHrP-induced vasodilation of the rabbit kidney were investigated. Immunostaining of human kidney revealed the abundant presence of PTHrP in media and intima of all microvessels as well as in macula densa. In isolated perfused rabbit kidney preconstricted with noradrenaline, 10(-5) M Rp-cAMPS, a direct inhibitor of protein kinase A, produced comparable inhibition of 2.5 x 10(-7) M forskolin- and 10(-7) M PTHrP-induced vasorelaxations. Renal vasorelaxation and renal microvessel adenylyl cyclase stimulation underwent comparable desensitization following exposure to PTHrP. Nitric oxide (NO)-synthase inhibition by L-NAME (10(-4) M), NO scavenging by an imidazolineoxyl N-oxide (10(-4) M) and guanylyl cyclase inhibition by methylene blue (10(-4) M) decreased PTHrP-induced vasorelaxation by 27 to 53%, abolished bradykinin-induced vasorelaxation and did not affect forskolin-induced vasorelaxation. The effects of Rp-cAMPS and L-NAME were not additive on PTHrP-induced vasorelaxation. Damaging endothelium by treating the kidney with either anti-factor VIII-related antibody and complement, gossypol or detergent, did not affect PTHrP- or forskolin-induced vasorelaxations but reduced bradykinin-induced vasorelaxation by 53 to 92%. Conversely, endothelial damage did not alter the inhibitory action of L-NAME on PTHrP-induced vasorelaxation. In conclusion, PTHrP is present throughout the human renovascular tree and juxtaglomerular apparatus. Activation of both adenylyl cyclase/protein kinase A and NO-synthase/guanylyl cyclase pathways are directly linked to the renodilatory action of PTHrP in a way that does not require an intact endothelium in the isolated rabbit kidney.
...
PMID:Parathyroid hormone-related protein detection and interaction with NO and cyclic AMP in the renovascular system. 891 26

Nitric oxide (NO) has been shown to be a potent vasodilator released from endothelial cells (EC) in large blood vessels, but NO release has not been examined in the capillary bed. Because the capillary bed represents the largest source of EC, it may be the largest source of vascular NO. In the present study, we used intravital microscopy to examine the effect of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on the microvasculature of the rat extensor digitorum longus muscle. L-NAME (30 mM) applied locally to a capillary (300 micron(s) from the feeding arteriole) reduced red blood cell (RBC) velocity [VRBC; control VRBC = 238 +/- 58 (SE) micron/s; delta VRBC = -76 +/- 8%] and RBC flux (4.4 +/- 0.7 to 2.8 +/- 0.7 RBC/s) significantly in the capillary, but did not change feeding arteriole diameter (Dcon = 6.3 +/- 0.7 micron, delta D = 5 +/- 7%) or draining venule diameter (Dcon = 10.1 +/- 0.6 micron, delta D = 4 +/- 2%). Because of the VRBC change, the flux reduction was equivalent to an increased local hemoconcentration from 1.8 to 5 RBCs per 100 micron capillary length. L-NAME also caused an increase in the number of adhering leukocytes in the venule from 0.29 to 1.43 cells/100 micron. L-NAME (30 mM) applied either to arterioles or to venules did not change capillary VRBC. Bradykinin (BK) locally applied to the capillary caused significant increases in VRBC (delta VRBC = 111 +/- 23%) and in arteriolar diameter (delta D = 40 +/- 5%). This BK response was blocked by capillary pretreatment with 30 mM L-NAME (delta VRBC = -4 +/- 27%; delta D = 5 +/- 9% after BK). We concluded that NO may be released from capillary EC both basally and in response to the vasodilator BK. We hypothesize that 1) low basal levels of NO affect capillary blood flow by modulating local hemoconcentration and leukocyte adhesion, and 2) higher levels of NO (stimulated by BK) may cause a remote vasodilation to increase microvascular blood flow.
...
PMID:Nitric oxide release in rat skeletal muscle capillary. 892 76

1. Changes in the release of nitric oxide (NO) in vivo were studied in rats following the administration of endothelium-dependent and -independent vasodilators as well as the NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). NO production was assessed by measuring variations of nitrate in plasma by capillary ion analysis. 2. Intravenous administration of the endothelium-dependent vasodilators, bradykinin (2 and 10 micrograms kg-1 min-1) or substance P (0.3-3 micrograms kg-1 min-1) caused a transient dose-dependent hypotension followed by an increase in plasma nitrate concentration (maximal increments: 33 +/- 5% and 38 +/- 6%, for bradykinin and substance P, respectively). Prior administration of L-NAME (10 mg kg-1 min-1) inhibited the hypotension and increase in plasma nitrate caused by these substances. Intravenous administration of sodium nitrate (200 micrograms kg-1) also produced a transitory elevation in plasma nitrate which was similar in magnitude as that caused by the vasodilators. A rapid and transitory increment in plasma nitrate was observed after i.v. administration of authentic NO (400 micrograms kg-1). 3. Rats receiving the endothelium-dependent vasodilators, prostacyclin (0.6 micrograms kg-1 min-1) or adenosine (3 mg kg-1 min-1) intravenously showed a drop in blood pressure paralleled by a decrease in plasma nitrate (maximal decreases: 34 +/- 5% and 24 +/- 4%, for prostacyclin and adenosine, respectively). A similar effect on the plasmatic concentration of nitrate was observed when L-NAME (10 mg kg-1 min-1, i.v.) was administered to the animals. 4. This study demonstrates that (i) changes in plasma nitrate can be detected in vivo after stimulation or inhibition of NO synthase, (ii) an increased production of NO, measured as plasma nitrate, is related to the hypotension caused by bradykinin and substance P and (iii) a diminished concentration of plasmatic nitrate is associated to the hypotension induced by adenosine or prostacyclin (endothelium-independent vasodilators), suggesting that the L-arginine: NO pathway is capable of rapid down-regulation in response to a fall in blood pressure.
...
PMID:Changes in nitric oxide release in vivo in response to vasoactive substances. 893 25

The effects of endotoxin (20 mg kg-1 i.p.) on the mesenteric vascular responses to acetylcholine, bradykinin, sodium nitroprusside, and to transient occlusion of the superior mesenteric artery were examined in rats anesthetized with pentobarbitone. Mesenteric vasodilator responses to close arterial injections of acetylcholine and bradykinin were reduced at 1.5 h after endotoxin and almost abolished by 4 h; responses to sodium nitroprusside were unaffected. Occlusion of the superior mesenteric artery for 30, 60, or 120 s produced, on release of the occlusion, a time-dependent vasodilator response in the mesenteric circulation (post-occlusion hyperemia). This hyperemia was markedly reduced by nitro-L-arginine methyl ester (L-NAME); L-NAME did not modify acetylcholine-induced vasodilation. Endotoxin-pretreatment did not modify mesenteric post-occlusion hyperemia 1.5 h after administration but markedly reduced the response by 2.5 h. The administration of L-NAME to endotoxin-treated rats did not further attenuate the hyperemic responses. Mesenteric vasoconstrictor responses to phenylephrine were not modified by endotoxin, although systemic pressor responses to this agent were impaired. We concluded that endotoxin impairs endothelium and nitric oxide-dependent vasodilator responses in the mesenteric circulation.
...
PMID:Endotoxin-induced inhibition of mesenteric vasodilator responses to acetylcholine, bradykinin, and post-occlusion hyperemia in anesthetized rats. 894 54

Responses to and the mechanism of action of adrenomedullin (ADM), the carboxy-terminal fragments of ADM, and calcitonin gene-related peptide (CGRP), a structurally related peptide, were investigated in the pulmonary vascular bed of the rat. Under conditions of elevated tone and controlled pulmonary blood flow in the isolated blood-perfused rat lung, injections of ADM, the 15-52 amino acid carboxy-terminal ADM analogue (ADM15-52), and CGRP caused dose-related decreases in pulmonary arterial perfusion pressure. In contrast, the carboxy-terminal 22-52 and 40-52 amino acid fragments had no consistent vasodilator activity. After administration of the nitric oxide synthase inhibitors, N omega-nitro-L-arginine benzyl ester or N omega-nitro-L-arginine methyl ester (L-NAME), pulmonary vasodilator responses to ADM, to ADM15-52, to CGRP, to acetylcholine, and to bradykinin were significantly decreased in the rat, whereas vasodilator responses to isoproterenol and nitroglycerin were not changed. However, in the pulmonary vascular bed of the cat, L-NAME had no significant effect on vasodilator responses to ADM in doses that attenuated vasodilator responses to acetylcholine and bradykinin. L-NAME had no effect on responses to isoproterenol or nitric oxide. When the relative vasodilator activity of the active peptides was compared, ADM15-52 was approximately three-fold less potent than ADM, and ADM was threefold less potent than CGRP in decreasing pulmonary vascular resistance in the rat lung. When vasodilator responses were compared in the rat and cat, ADM was threefold more potent in decreasing pulmonary vascular vascular resistance in the cat than in the rat, and vasodilator responses to ADM were independent of the intervention used to raise tone in the rat. The present data demonstrate that ADM and ADM15-52 have significant vasodilator activity in the pulmonary vascular bed of the rat, and that responses to ADM, ADM15-52, and CGRP are dependent on the release of nitric oxide in the rat. The present results indicate that pulmonary vasodilator responses to ADM are not dependent on the release of nitric oxide in the cat and suggest that responses to the peptide are mediated by different mechanisms in the pulmonary vascular bed of the rat and cat.
...
PMID:Pulmonary vasodilator responses to adrenomedullin are reduced by NOS inhibitors in rats but not in cats. 896 12

Vascular tone has been shown to be importantly influenced by flow-induced release of endothelium-derived vasodilators. The purpose of the present study was to test the hypothesis that in porcine coronary resistance-size arterioles, flow-induced vasodilation is sensitive to oxygen tension. Arterioles (55-150 mu m) were studied in vitro under conditions of constant intraluminal pressure to dynamically measure arteriolar diameter in response to changes in flow or, alternatively, in response to bradykinin under three conditions: hyperoxia (pO(2) 400 mm Hg), normoxia (pO(2) 160 mm Hg), and hypoxia (p0(2) 40 mm Hg). Under conditions of constant pressure and no flow, hypoxia alone resulted in vasodilation that was blocked by the nitric oxide synthase inhibitor omega-nitro-L-arginine methyl ester (L-NAME). Hypoxia did not alter the vasodilator response to bradykinin when compared to the vasodilator response to bradykinin during normoxia. During hyperoxia, flow-induced vasodilation was significantly reduced by either indomethacin, or L-NAME. Indomethacin and L-NAME combined completely abolished flow-induced vasodilation under conditions of hyperoxia. Under conditions of normoxia and hypoxia, indomethacin or L-NAME alone only partially blocked flow-induced vasodilation. No further inhibition was observed when indomethacin and L-NAME were combined. Glybenclamide failed to alter flow-induced vasodilation either alone or in combination with indomethacin and L-NAME. The results suggest that the mechanisms responsible for flow-induced vasodilation in coronary arterioles are complex and are different depending upon the oxygen tension. During hyperoxia, vasodilation is due to the combined actions of prostanoids and nitric oxide, while under conditions of normoxia and hypoxia, flow-induced vasodilation is the result of not only prostanoids and nitric oxide, but of another as of yet unidentified oxygen-sensitive endogenous vasodilator.
...
PMID:Effects of oxygen tension on flow-induced vasodilation in porcine coronary resistance arterioles. 899 34

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>