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)

The effect of diatrizoate (Urografin325) on the cumulative dose-response curve of the vasodilatory response to acetylcholine was studied in the isolated perfused rat kidney (IPRK). The effect of 1-nitroarginine methyl ester (L-NAME) (10 mumol l-1) on the cumulative concentration-response curve of the vasodilatory response to acetylcholine and sodium nitroprusside was also studied. Acetylcholine is a vasodilator dependent on nitric oxide (NO) synthesis by the endothelium; sodium nitroprusside is a vasodilator not dependent on endogenous NO synthesis and L-NAME is an inhibitor of endogenous NO synthesis. The effect of L-NAME (10 mumol l-1) on the vasodilatory effect of diatrizoate which is observed in the presence of endothelin A receptor antagonist (BQ123, 10 mumol l-1) was also studied. In all experiments an infusion of angiotensin II (5 ng min-1) was maintained to increase the vascular tone of the preparation. Acetylcholine induced vasodilatation and the maximum increase in renal perfusate flow (RPF) was 17.0 +/- 1.7%, (p < 0.05). Diatrizoate (20 mgl ml-1 perfusate concentration) which induced a sustained fall in the RPF (-31.0 +/- 1.7%, p < 0.05) had no effect on the vasodilatory response to acetylcholine, and a similar increase in the RPF (17.8 +/- 2.2%, p < 0.05) was observed. In contrast, L-NAME (10 mumol l-1) completely abolished the vasodilatory effect of acetylcholine and produced instead a modest decrease in RPF by -5.0 +/- 1.7% (p < 0.05). The vasodilatory effect of sodium nitroprusside was not affected by L-NAME, confirming its selectivity as an inhibitor of endogenous NO synthesis in the IPRK. The maximum increase in the RPF induced by sodium nitroprusside was 23.1 +/- 2.0% (p < 0.05) in the absence of L-NAME and 21.2 +/- 2.2% (p < 0.05) in its presence. L-NAME did not interfere with the vasodilatation induced by diatrizoate in the presence of BQ123. In the presence of BQ123 alone the RPF increased from 23.3 +/- 1.4 ml min-1 g-1 to 26.5 +/- 1.0 ml min-1 g-1 (p < 0.05). In the presence of L-NAME and BQ123 the RPF increased from 24.4 +/- 3.0 ml min-1 g-1 to 27.2 +/- 2.7 ml min-1 g-1 (p < 0.05). There was no difference between the two groups (p > 0.05). In conclusion, diatrizoate did not interfere with endothelium derived NO-dependent vasodilatation in the kidney. A reduced production of NO in the vascular endothelium induced by contrast media is unlikely to play any role in the pathophysiology of the increase in renal vascular resistance produced by these agents. The renal vasodilatation induced by diatrizoate is not dependent on endogenous production of NO.
...
PMID:Effect of radiographic contrast media on endothelium derived nitric oxide-dependent renal vasodilatation. 913 41

We studied rabbit isolated erectile tissue responses to changes in preload and to active tension development with norepinephrine. The effects of antagonists of endothelin-1, prostaglandins E2 and F2alpha and of nitric oxide were also tested on normal and de-endothelialized preparations. Tissue distension was found to elicit spontaneous rhythmic contractions. Increase in preload diminished the latency of the spontaneous activity and augmented the developed force. Active tension development and the inhibitor of the Na+,K+ pump, ouabain, opposed the spontaneous activity. A marked reduction in the resting tension with abolition of the spontaneous activity was observed on normal, but not on de-endothelialized tissues, following the addition of the specific prostaglandin E2 and F2alpha receptor antagonist, SC-19220. At 3 x 10(-4) M, the highest concentration used, the endothelin-A receptor antagonist BQ-123 failed to change the pattern of the spontaneous activity and the resting tension of normal tissues. The nitric oxide synthesis inhibitor, L-NAME, did not produce reliable effects. These findings point to a causal relation between cavernosal tissue distension and phasic and tonic contractions. Phasic contractions appear to be elicited by smooth muscle cells through the enzyme Na+,K+-ATPase. Increase in the resting tone could be mediated, at least in part, by the endothelium, through the release of prostaglandins E2 and/or F2alpha but not of endothelins. We discuss the hypothesis that, in cavernosal tissue, mechanotransduction of distension to contractile responses is an important determinant of detumescence.
...
PMID:Functional response of cavernosal tissue to distension. 953 95

We measured the activity of mitogen-activated protein (MAP) kinases, enzymes believed to be involved in the pathway for cell proliferation, in rat aortic strips with or without endothelium, and examined effects of angiotensin receptor antagonists, endothelin receptor antagonists and nitric oxide (NO)-related agents. Endothelium removal produced an activation of MAP kinase activity in the strips, whereas the enzyme activity was not affected in the adventitia. The MAP kinase activation was inhibited by either the angiotensin AT1 receptor antagonist losartan or the endothelin ETA receptor antagonist BQ 123. The combination of both antagonists caused an additive inhibition. The angiotensin AT2 receptor antagonist PD 123,319 and the endothelin ETB receptor antagonist BQ 788 did not affect the MAP kinase activation. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) caused an activation of MAP kinase in the endothelium-intact aorta and the MAP kinase activation was inhibited by losartan or BQ123. The NO releaser nitroprusside inhibited the MAP kinase activation induced by endothelium removal or angiotensin II. These results suggest that even in isolated arteries, NO of endothelial origin tonically exert MAP kinase-inhibiting effects and endogenous angiotensin II and endothelins in the media are tonically released to cause MAP kinase-stimulating effects in medial smooth muscle.
...
PMID:Evidence that angiotensin II, endothelins and nitric oxide regulate mitogen-activated protein kinase activity in rat aorta. 965 1

To analyze newborn cerebrovascular autoregulation, middle cerebral arteries from 3-4-d-old piglets were cannulated, and diameter changes after transmural pressure variation were measured. After an equilibration period at 30 mm Hg, pressure was modified from 10 to 70 mm Hg in 20-mm Hg steps. Segments with endothelium showed vasodilation during pressure decrease and vasoconstriction during pressure increase. In each case the maximum response was about 5% that of the resting diameter. Segments without endothelium responded passively to pressure change. Vasodilation during pressure decrease was reduced by the preferential calcium-activated potassium (KCa) channel blocker, tetraethylammonium (1 mM), and was absent with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methylester (L-NAME, 10 microM). The NO synthase substrate, L-arginine (10 microM), counteracted the dilation blockade caused by L-NAME. The cyclooxygenase inhibitor indomethacin (10 microM) and the endothelin A receptor antagonist BQ-123 (10O microM) eliminated the pressure increase-induced vasoconstriction. The ATP-sensitive potassium channel blocker, glibenclamide (1 microM), and the endothelin B receptor antagonist, BQ-788 (10 nM), did not modify the autoregulatory response. None of these drugs modified the passive changes produced by pressure variations in segments without endothelium. These results suggest that: 1) piglet middle cerebral artery autoregulation is endothelium-dependent; 2) NO and KCa channels are involved in vasodilation during transmural pressure decrease, and 3) endothelin-1, through endothelin A receptors, and prostanoids mediate vasoconstriction during pressure increase.
...
PMID:Endothelial factors and autoregulation during pressure changes in isolated newborn piglet cerebral arteries. 970 8

The contractile actions of the proteinase-activated receptor-2-activating peptides (PAR2APs), SLIGRL-NH2 (SL-NH2), SLIGKV-NH2 (KV-NH2), trans-cinnamoyl-LIGRLO-NH2 (tc-NH2), and the PAR1-AP. TFLLR-NH2 (TF-NH2) as well as trypsin and thrombin were studied in endothelium-denuded and intact human umbilical vein (HUV) ring preparations. In HUV rings with, but not without an intact endothelium, PAR2APs caused a concentration-dependent contractile response, whereas LSIGRL-NH2 trypsin and PAR1APs were inactive. The contractile response was not affected by the endothelin ETA receptor antagonist, BQ123, the cyclooxygenase inhibitor, indomethacin, the leukotriene synthesis inhibitor, MK886, or the epoxygenase/P450 inhibitor, SKF-525A. Other pharmacological antagonists (prazosin, Losartan") were similarly inactive. The order of potencies of the PAR2APs to cause a contraction in the endothelium-intact preparation was: SL-NH2 > > KV-NH2 > or = tc-NH2. Using an endothelium-free rat aorta ring as a reporter tissue, surrounded with endothelium-intact HUV as a donor tissue in a 'sandwich assay,' we also monitored the ability of SL-NH2, TF-NH2, trypsin and thrombin to release either contractile (EDCF) or relaxant (EDRF) factors. In the 'sandwich assay' done in the presence of L-NAME (0.1 mM), the endothelium-intact HUV tissue (but not endothelium-denuded HUV) released a contractile factor (EDCF) in response to SL-NH2 (50 microM) but not to trypsin or LSIGRL-NH2. The SL-NH2-mediated release/action of the EDCF was not affected by BQ123, indomethacin, MK886 or SKF-525A. In the 'sandwich assay', trypsin (4-10 nM), SL-NH2, KV-NH2 and tc-NH2 caused the release of a relaxant activity (EDRF) from the endothelium-intact (but not the denuded) HUV preparation. The release of EDRF was blocked by 0.1 mM (omega)nitro-L-arginine-methylester (L-NAME). Neither thrombin (10 u ml(-1), 100 nM) nor TF-NH2 (50 microM) were active in this EDRF-release assay. The relative potencies of the PAR2 agonists for causing the release of EDRF in the HUV sandwich assay were: trypsin> >SL-NH2> >tc-NH2>KV-NH2. This order of potencies differed from the one observed for the same agonists in the HUV contraction assay (above) and in an intracellular calcium signalling assay, conducted with cloned human PAR2 that was expressed in cultured rat kidney KNRK cells: trypsin > > SL-NH2 = tc-NH2 > KV-NH2. We conclude that PAR2APs (but not PAR1APs) via a receptor distinct from PAR2, can cause a contractile response in endothelium-intact HUV tissue via the release of a diffusable EDCF, that is different from previously recognized smooth muscle agonists (e.g. prostanoid metabolites, endothelin, noradrenaline, angiotensin-II, acetylcholine).
...
PMID:Endothelium-dependent contractile actions of proteinase-activated receptor-2-activating peptides in human umbilical vein: release of a contracting factor via a novel receptor. 988 72

Eight Na-repleted volunteers underwent 3 separate 90-minute infusions of either N(G)-nitro-L-arginine methyl ester (L-NAME) 3.0 mg. kg(-1). min(-1) or endothelin-A receptor (ET-A) blocker BQ-123 (BQ) 0.125 nmol. kg(-1). min(-1) or both. Mean arterial pressure (MAP), glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistances (RVR), and sodium excretion rate (UNaV) were measured at baseline (b) and from 0 to 45 minutes (period 1) and 45 to 90 minutes (period 2) of infusion. BQ alone had no effect. GFR declined by 4.9% (P<0.001 versus b) in period 1, to 9.9% (P<0. 001) in period 2 with L-NAME, and by 3.3% (P<0.01) to 6.6% (P<0.001) with L-NAME plus BQ (P=NS between L-NAME and L-NAME plus BQ). UNaV fell equally with L-NAME or L-NAME plus BQ. MAP rose significantly in period 2 with L-NAME (6.9%; P<0.001) but not with coinfused BQ (2. 1%; P=NA versus b, P=0.005 versus L-NAME alone). RBF declined by 12. 2% (P<0.001) to 18.3% (P<0.001) with L-NAME and by 4.6% (P<0.005) to 8.2% (P<0.001) with L-NAME plus BQ. These changes were smaller with L-NAME plus BQ (P<0.05 in period 1 and P<0.02 in period 2). Blunted changes were also seen for RVR (P<0.005 in period 1 and P<0.001 in period 2 between L-NAME alone and L-NAME plus BQ). These findings show that systemic and renal vasoconstriction due to L-NAME are attenuated by BQ, which suggests that an interaction between endogenous nitric oxide production and ET-A activity participates in the maintenance of baseline systemic and renal vascular tone in humans.
...
PMID:Endothelin-A blockade attenuates systemic and renal hemodynamic effects of L-NAME in humans. 1064 52

The actions of the blood substitute diaspirin crosslinked hemoglobin (DCLHb) were investigated in rat (small mesenteric artery) and human (radial collateral artery) resistance vessels mounted in a wire myograph for isometric tension recording. DCLHb did not contract resting vessels from rats, but vasoconstrictor responses were observed in isolated arteries and perfused mesenteric beds prestimulated with threshold concentrations of methoxamine. The DCLHb contractile responses were greatly attenuated by N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) or endothelial removal, whereas BQ-123 (endothelin A receptor antagonist), prazosin (alpha1-adrenoceptor antagonist), or indomethacin (cyclooxygenase inhibitor) had no effect. Endothelium-dependent relaxations to carbachol in both rat mesenteric and human radial collateral artery were inhibited by DCLHb. Relaxations to carbachol were studied in the presence of L-NAME or 25 mM KCl to investigate the effect of DCLHb on endothelium-derived hyperpolarizing factor (EDHF) and nitric oxide, respectively. In both rat and human vessels, EDHF-mediated relaxations were not affected by DCLHb preincubation, whereas the nitric oxide component of carbachol-induced relaxations was practically abolished. In conclusion, inhibition of the effects of basal nitric oxide release underpins the vasoconstrictor effects of DCLHb. DCLHb effectively abolishes the nitric oxide component of carbachol-induced relaxation, with no effect on the EDHF-mediated component in both isolated rat mesenteric and human radial collateral arteries.
...
PMID:Effect of the blood substitute diaspirin crosslinked hemoglobin in rat mesenteric and human radial collateral arteries. 1130 Jun 52

We investigated the role of angiotensin II and endothelin-1 using the angiotensin AT1 receptor antagonist losartan and the endothelin ETA receptor antagonist atrasentan, in malignant hypertension and renal failure and damage induced by nitric oxide (NO) synthase inhibition in Harlan Sprague-Dawley (SD) rats. We also evaluated whether the protective effects of losartan go beyond the blood pressure reduction. Within only 3 weeks of treatment with the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME), Harlan SD rats developed malignant hypertension with renal failure and injuries. The latter were comprised of fibrinoid necrosis of small arteries and glomerular and tubular necrosis. Although both losartan and atrasentan attenuated the development of hypertension and renal failure, losartan only prevented the renal damage. In contrast to antrasentan, the vasodilator hydralazine reduced blood pressure and prevented the renal injuries similar to losartan. However, when these treatments were prolonged to 5 weeks, losartan, but not hydralazine, was still effective in reducing renal failure and damage, despite a marked increase in blood pressure. Our results indicate that angiotensin II and endothelin-1 play a differential role in the pathogenesis of malignant hypertension and in vascular and renal damage induced by L-NAME in Harlan SD rats. Although the protective effects of atrasentan may depend on the reduction of blood pressure, which was shown to retard the development of renal injury using hydralazine, those of losartan go beyond the blood pressure reduction. Hence, tissue protective effects of angiotensin AT1 receptor blockade may be pivotal for long-term vascular and renal protection.
...
PMID:Protective effects of angiotensin AT1 receptor blockade in malignant hypertension in the rat. 1932 69

The purpose of this study was to investigate the roles of endothelium-derived factors in the retinal arteriolar responses to acute severe elevation in systemic blood pressure (BP) in cats. Acute elevation of mean arterial BP by 60% for 5 min was achieved by inflating a balloon-tipped catheter in the descending aorta. The retinal arteriolar diameter, flow velocity, wall shear rate (WSR) and blood flow (RBF) changes during BP elevation were assessed with laser Doppler velocimetry 2 h after intravitreal injections of nitric oxide (NO) synthase inhibitor l-NAME, cyclooxygenase inhibitor indomethacin, endothelin-1 receptor antagonists (BQ-123 for type A and BQ-788 for type B), or Rho kinase inhibitor fasudil. BP elevation caused a marked increase in retinal arteriolar flow velocity and WSR with slight vasoconstriction, resulting in an increase in RBF. The increases in velocity, WSR and RBF, but not diameter, were correlated with the increase in ocular perfusion pressure. With l-NAME or indomethacin, the increase in RBF upon BP elevation was significantly attenuated due to enhanced retinal arteriolar vasoconstriction. In contrast, BQ-123 and fasudil potentiated the increased RBF. BQ-788 had no effect on arteriolar diameter and hemodynamics. Our data suggest that acute elevation of BP by 60% leads to an increase in RBF due to the release of NO and prostanoids probably through a shear stress-induced vasodilation mechanism. The release of endothelin-1 and Rho kinase activation help to limit RBF augmentation by counteracting the vasodilation. It appears that the retinal endothelium, by releasing vasoactive substances, contributes to RBF regulation during acute severe elevation of systemic blood pressure.
...
PMID:Retinal arteriolar responses to acute severe elevation in systemic blood pressure in cats: role of endothelium-derived factors. 2294 Mar 70

Endothelin-1 (ET-1) is essential for mammalian development and life, but it has also been implicated in increased cardiovascular risk under pathophysiological conditions. The aim of this study was to determine the impact of endothelial overexpression of the prepro-endothelin-1 gene on endothelium-dependent and endothelium-independent responses in the conduit and renal arteries of lean and obese mice. Obesity was induced by high-fat-diet (HFD) consumption in mice with Tie-1 promoter-driven, endothelium-specific overexpression of the prepro-endothelin-1 gene (TET^het) and in wild-type (WT) littermates on a C57BL/6N background. Isometric tension was measured in rings (with endothelium) of the aorta (A), carotid (CA) and iliac (IA) arteries as well as the main (MRA) and segmental renal (SRA) arteries; all experiments were conducted in the absence or presence of L-NAME and/or the COX inhibitor meclofenamate. The release of prostacyclin and thromboxane A2 was measured by ELISA. In the MRA, TET^het per se increased contractions to endothelin-1, but the response was decreased in SRA in response to serotonin; there were also improved relaxations to acetylcholine but not insulin in the SRA in the presence of L-NAME. HFD per se augmented the contractions to endothelin-1 (MRA) and to the thromboxane prostanoid (TP) receptor agonist U46619 (CA, MRA) as well as facilitated relaxations to isoproterenol (A). The combination of HFD and TET^het overexpression increased the contractions of MRA and SRA to vasoconstrictors but not in the presence of meclofenamate; this combination also augmented further relaxations to isoproterenol in the A. Contractions to endothelin-1 in the IA were prevented by endothelin-A receptor antagonist BQ-123 but only attenuated in obese mice by BQ-788. The COX-1 inhibitor FR122047 abolished the contractions of CA to acetylcholine. The release of prostacyclin during the latter condition was augmented in samples from obese TET^het mice and abolished by FR122047. These findings suggest that endothelial TET^het overexpression in lean animals has minimal effects on vascular responsiveness. However, if comorbid with obesity, endothelin-1-modulated, prostanoid-mediated renal arterial dysfunction becomes apparent.
...
PMID:Endothelial overexpression of endothelin-1 modulates aortic, carotid, iliac and renal arterial responses in obese mice. 2821 25

1 2 Next >>