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Query: UMLS:C0406810 (
NAME
)
13,345
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
1 We have determined the dermal microvascular effects of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 100 nmol/site),
endothelin-1
(ET-1, 0.1-10 pmol/site) and ET-3 (0.1-30 pmol/site) in rats with streptozotocin (STZ)-induced diabetes mellitus. Cutaneous blood flow changes as measured by a 133xenon (133Xe) clearance technique, were determined in diabetic rats four weeks after treatment with streptozotocin (STZ) and compared with responses measured in normal rats four weeks after treatment with saline. 2 Resting skin blood flow was similar in diabetic and in normal rats, as measured by 133Xe clearance and laser Doppler flowmetry. 3 Intradermal NG-nitro-L-arginine methyl ester (L-NAME) reduced skin blood flow in normal rats by 55.2 +/- 2.6% as measured by 133Xe clearance, (n = 9). L-
NAME
was significantly less effective in diabetic rats, inducing a 40.9 +/- 7.7% decrease in blood flow (n = 9, P less than 0.05). The enantiomer D-
NAME
had no effect in either group of rats. 4 Low doses of ET-1 and ET-3 injected intradermally induced dose-dependent decreases in blood flow, measured by 133Xe clearance, which were similar in both groups of rats. However, the responses to the highest doses of ET-1 (10 pmol/site) and ET-3 (10 and 30 pmol/site) were significantly reduced in the diabetic compared with the normal rats (P less than 0.05).In addition vasoconstriction to the highest doses of vasopressin (0.3 and 3 pmol/site) and vasodilatation to the neuropeptide calcitonin gene-related peptide (CGRP, 1O pmol/site) were similarly reduced in the diabetic rats (P <0.05).5. The decrease in blood flow induced by submaximal doses of ET-1 was enhanced by co-injection with L-
NAME
(100 nmol/site) in both diabetic and normal rats. However, this enhanced response was significantly reduced in the diabetic rats (P<0.05). A similar pattern of responses were observed to ET-3 in the presence and absence of L-
NAME
.6. These results indicate that the cutaneous microvasculature of rats with STZ-induced diabetes responds differently to intradermal ET-1 and ET-3 compared with normal rats; a similarly altered vascular reactivity was observed with vasopressin and CGRP. Hence, the diabetic microcirculation has impaired responses to several vasoconstrictors and a vasodilator. The effect of the nitric oxide synthase inhibitor L-
NAME
is also suppressed in the diabetics, suggesting that there may be decreased local production of, or response, to nitric oxide.
...
PMID:Altered microvascular reactivity to endothelin-1, endothelin-3 and NG-nitro-L-arginine methyl ester in streptozotocin-induced diabetes mellitus. 139 77
Our previous studies have shown that
endothelin-1
(
ET-1
) induces an initial relaxation followed by a contraction in the guinea-pig ileum. To test whether other ET isopeptides (ET-2, ET-3, vasoactive intestinal contractor (VIC) and sarafotoxin S6b) and big
ET-1
, the
ET-1
precursor, also induce similar biphasic responses, we compared their effects in isolated guinea-pig ileum. In addition, the mechanism of initial relaxation was studied. At 1-100 nM,
ET-1
, ET-2 and VIC were equipotent in producing the biphasic responses. S6b also produced similar biphasic responses, except that only a relaxation was elicited at 1 nM. ET-3 was approximately 30- to 100-fold less active than
ET-1
in producing the contraction, whereas it was as potent as
ET-1
in producing relaxation. Big
ET-1
induced a relaxation of slower onset and longer duration, followed by a weak contraction at concentrations higher than 30 nM. The initial relaxation produced by
ET-1
was not affected by pretreatment with L-
NAME
(NW-nitro-L-arginine methyl ester), hemoglobin, 9-AC (anthracene-9-carboxylic acid), SITS (4-acetamido-4'-isothiocyanatostilbene-2-2'-disulfonic acid), glibenclamide, ouabain, phorbol 12,13-dibutyrate, sodium nitroprusside, human atrial natriuretic peptide (hANP) or forskolin, whereas it was abolished by pretreatment with apamin. Although phorbol 12,13-dibutyrate pretreatment had no significant effect on the biphasic response of
ET-1
, it rapidly reversed the sustained contraction produced by
ET-1
. These results indicate that the initial relaxation is caused by the activation of Ca(2+)-activated K+ channels.
...
PMID:Intestinal relaxation by endothelin isopeptides: involvement of Ca(2+)-activated K+ channels. 142 64
1. The effects of NG-nitro-L-arginine (L-NNA), NG-nitro-L-arginine methyl ester (L-
NAME
), haemoglobin and methylene blue have been examined on vascular reactivity in the rat isolated caudal artery. The effects of L-NNA and sodium nitroprusside were also investigated on the stimulation-induced (S-I) efflux of noradrenaline in the rat caudal artery. 2. L-NNA (10 microM) and L-
NAME
(10 microM) significantly attenuated the vasodilator responses to acetylcholine (1 nM-1 microM), but had no effect on vasodilator responses to papaverine (1-100 microM). 3. Vasoconstrictor responses to sympathetic nerve stimulation (3 Hz, 10 s), noradrenaline (0.01-1 microM), methoxamine (1-10 microM), 5-hydroxytryptamine (0.01-0.3 microM), phenylephrine (0.1-10 microM),
endothelin-1
(10 nM) and KCl (40 mM) were significantly enhanced by 10 microM L-NNA. L-
NAME
(10 microM) caused a significant enhancement of vasoconstrictor responses to noradrenaline and sympathetic nerve stimulation in endothelium-intact, but not in endothelium-denuded tissues. 4. Haemoglobin and methylene blue (both 10 microM) enhanced the vasoconstrictor responses to sympathetic nerve stimulation and noradrenaline. The enhancements were absent in endothelium-denuded arterial segments. 5. In endothelium-denuded arterial segments precontracted with phenylephrine, the vasodilator responses to the nitric oxide donor, sodium nitroprusside (0.1-300 nM) were decreased by increasing the level of precontraction. 6. L-NNA (10 microM) had no effect on the S-I efflux of radioactivity from arteries in which transmitter stores had been labelled with [3H]-noradrenaline. 7. These results suggest that endothelial nitric oxide attenuates vasoconstrictor responses in the rat caudal artery through activation of soluble guanylate cyclase to decrease smooth muscle contractility. Therefore, the findings provide evidence that nitric oxide acts as a functional antagonist to oppose vasoconstriction.
...
PMID:Attenuation of vasoconstriction by endogenous nitric oxide in rat caudal artery. 146 34
1. The role of nitic oxide (NO) derived from L-arginine in the regional vasodilator effects of
endothelin-1
has been investigated in anaesthetized, spontaneously hypertensive (SH) rats in which autonomic reflexes were abolished by ganglion blockade. The experimental design incorporated animals infused with phenylephrine to mimic the peripheral vasconstrictor effects of the NO biosynthesis inhibitors and a single dose per animal paradigm to obviate problems of tachyphylaxis to the vasodilator effects of
endothelin-1
. 2. Infusion of the inhibitor of NO synthase, N-monomethyl-L-arginine (L-NMMA) at a dose (5 mg kg-1 min-1) which maximally raised blood pressure did not influence either the fall in blood pressure or the vasodilator responses induced in the hindquarters and carotid vascular beds by
endothelin-1
(1 nmol kg-1, i.v.) The duration (but not the initial magnitude) of the vasodepressor response to
endothelin-1
was however significantly attenuated (by 49%) during infusion of the more potent inhibitor of NO synthase, NG-nitro-L-arginine methyl ester (L-
NAME
), 2 mg kg-1 min-1. 3. Increasing the dose of L-
NAME
to 10 and 25 mg kg-1min-1 significantly attenuated, but did not abolish, the falls in blood pressure and hindquarters vasodilator responses to acetylcholine, 1 microgram kg-1, and
endothelin-1
, 1 nmol kg-1 min-1. The effects were selective in that vasodepressor responses to the endothelium-independent vasodilator, sodium nitroprusside, 1-10 micrograms kg-1 min-1, were unaltered. The effects were selective in that vasodepressor responses to the endothelium-independent vasodilator, sodium nitroprusside, 1-l0mg kg min , were unaltered.4. The data indicate that NO generated de novo from L-arginine mediates a significant component of the vasodilator effect of
endothelin-1
in the anaesthetized, ganglion-blocked SH rat. However, a major component of the vasodepressor effects of both
endothelin-1
and acetylcholine may occur independently of this mechanism.
...
PMID:The role of nitric oxide in the regional vasodilator effects of endothelin-1 in the rat. 162 60
1. The effects of cooling on the response of rabbit central ear artery to
endothelin-1
and the role of the endothelium in these effects were studied in 2 mm long cylindrical arterial segments. 2. Concentration-response curves for
endothelin-1
(10(-10)-3 x 10(-7) M) were recorded isometrically in arteries with and without endothelium at 37 degrees C and during cooling (24 degrees C). To analyze further the endothelial mechanisms of the response to
endothelin-1
during cooling, the effects of this peptide in the presence of NG-nitro-L-arginine methyl ester (L-
NAME
) (10(-4) M) or meclofenamate (10(-5) M) were also determined. 3. In every condition tested,
endothelin-1
produced a marked, concentration-dependent arterial contraction. Sensitivity of intact arteries to this peptide was consistently lower at 24 degrees C than at 37 degrees C. At 37 degrees C there were comparable responses of arteries with and without endothelium, but at 24 degrees C arteries without endothelium showed a higher sensitivity than intact arteries to
endothelin-1
. 4. L-
NAME
(10(-4) M) increased the maximal contraction at 37 degrees C, and both the sensitivity and maximal contraction at 24 degrees C of intact arteries to
endothelin-1
. Meclofenamate (10(-5) M) did not affect the arterial response to
endothelin-1
. 5. Sensitivity of arteries with and without endothelium to nitroprusside (10(-9)-10(-3) M) was significantly decreased during cooling, and endothelium removal did not affect the relaxation to this nitrovasodilator. 6. These results suggest that cooling decreases sensitivity of cutaneous arteries (ear artery) to
endothelin-1
probably by increasing the availability of endothelial nitric oxide.
...
PMID:Response of rabbit ear artery to endothelin-1 during cooling. 179 25
1 We investigated the peripheral haemodynamic effects of human alpha-calcitonin gene-related peptide (CGRP) following administration of
endothelin-1
or NG-nitro-L-arginine methyl ester (L-
NAME
), an inhibitor of nitric oxide production, in conscious, chronically-instrumented, Long Evans rats. 2 Infusion of
endothelin-1
(3 nmol kg-1 h-1) caused hypertension, bradycardia and renal, mesenteric and hindquarters vasoconstrictions. Co-infusion of human alpha-CGRP (1.5 nmol kg-1 h-1) reduced the hypertension and abolished the hindquarters vasoconstriction caused by
endothelin-1
but the renal and mesenteric vasoconstrictor actions of
endothelin-1
were not affected. 3 Infusion of human alpha-CGRP (15 nmol kg-1 h-1) in the presence of
endothelin-1
caused hypotension and hyperaemic vasodilatation in the hindquarters; the mesenteric vasoconstrictor effects of
endothelin-1
were diminished, but there was only a transient reversal of the renal vasoconstrictor effects of
endothelin-1
. 4 Pretreatment with the non-peptide angiotensin II receptor antagonist, DuP 753 (10 mg kg-1), caused slight hypotension associated with renal, mesenteric and hindquarters vasodilatations, but DuP 753 did not affect responses to
endothelin-1
infusion. However, under these conditions co-infusion of human alpha-CGRP (15 nmol kg-1 h-1) caused a sustained reversal of the renal vasoconstrictor effects of
endothelin-1
. 5 These results indicate that the failure of human alpha-CGRP to cause sustained reversal of the renal vasoconstrictor effects of
endothelin-1
in the absence of DuP 753 was due to activation of the reninangiotensin system (possibly as a consequence of the hypotension). 6. In the second experiment, L-
NAME
(l0mgkg-1) caused renal, mesenteric and hindquarters vasoconstrictions similar to those seen in the presence of
endothelin-1
. However, the renal vasoconstrictor effects of L-
NAME
were reversed completely by human alpha-CGRP (l5nmolkg- h-1), even though the latter caused hypotension comparable to that seen in the presence of
endothelin-1
. These results are consistent with a lack of functional activation of the renin-angiotensin system by human alpha-CGRP in the presence of L-
NAME
. 7. The vasoconstrictor effects of L-
NAME
on the hindquarters were completely reversed by infusion of human alpha-CGRP, but hindquarters flow and vascular conductance did not rise above baseline levels. Hence these results indicate the hindquarters hyperaemic vasodilator effects of human alpha-CGRP seen in the presence of
endothelin-1
were contributed to by nitric oxide-mediated mechanisms.
...
PMID:Haemodynamic effects of human alpha-calcitonin gene-related peptide following administration of endothelin-1 or NG-nitro-L-arginine methyl ester in conscious rats. 187 60
1. Resting haemodynamic status and responses to
endothelin-1
(0.0004, 0.04, 0.4 nmol kg-1) and NG-nitro-L-arginine methyl ester (L-
NAME
, 10 mg kg-1) were assessed in conscious, Wistar rats treated with streptozotocin (STZ) to induce diabetes mellitus, and in control animals treated with saline. 2. In the resting state, STZ-treated rats had a bradycardia relative to control animals (291 +/- 13 and 337 +/- 10 beats min-1, respectively), but mean arterial blood pressures were the same in the two groups (STZ-treated 109 +/- 3; control 114 +/- 4 mmHg). However, the STZ-treated rats had raised renal (105 +/- 9 units) and mesenteric (114 +/- 16 units) vascular conductances and reduced hindquarters vascular conductance (26 +/- 4 units) relative to control rats (renal, 80 +/- 6; mesenteric, 75 +/- 7; hindquarters, 37 +/- 3 units). 3. Increasing doses of
endothelin-1
caused similar, early falls and subsequent rises in mean arterial blood pressures in both groups of rats. Although there were initial hindquarters vasodilatations with
endothelin-1
that were not different in STZ-treated and control rats, there were subsequent renal and mesenteric vasoconstrictions that were greater in the former. Hence, the similar rises in mean arterial blood pressures must have been accompanied by a greater reduction in cardiac output in the STZ-treated rats. 4. L-
NAME
caused similar renal and mesenteric vasoconstrictions in control and STZ-treated rats, but there was a smaller pressor effect and an attenuated hindquarters vasoconstrictor response to L-
NAME
in STZ-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:The effects of endothelin-1 and NG-nitro-L-arginine methyl ester on regional haemodynamics in conscious rats with streptozotocin-induced diabetes mellitus. 188 94
1. The isolated superior mesenteric arterial bed of the rat, perfused with Krebs-Henseleit solution containing 10 microM indomethacin, was used to study the effects of reducing dissolved O2 tension on the pressor responses to
endothelin-1
, endothelin-3 and sarafotoxin S6b. The modulation of these responses by the endothelium was investigated by removing the intima with the detergent CHAPS and, for
endothelin-1
, by inhibiting nitric oxide production with N omega-nitro-L-arginine methyl ester (L-
NAME
). Comparison was made with the effects of lowering O2 tension on the pressor responses to noradrenaline and 5-hydroxytryptamine. 2. Lowering the perfusate O2 tension from 551 +/- 2 mmHg to 14.0 +/- 0.5 mmHg did not change the ED50 for
endothelin-1
but its maximal responses (Rmax) were increased by 2.1 and 2.7 fold, respectively, in the presence and absence of endothelium. The Rmax values for endothelin-3 were also greater in hypoxia either in the presence (by 2.3 fold) or absence of the endothelium (by 1.6 times) but those for sarafotoxin S6b were only enhanced significantly by hypoxia in the absence of the intima. hypoxia reduced the potencies of endothelin-3 and sarafotoxin S6b whether or not endothelium was present. 3. Endothelial destruction, whether in hypoxic or oxygenated conditions, increased the Rmax values for
endothelin-1
and endothelin-3; at both O2 tensions those for endothelin-3 increased more than those for
endothelin-1
. The ED50 for
endothelin-1
was unchanged by destroying the endothelium but endothelin-3 was less potent in the absence of an endothelium than in its presence. Removal of the endothelium did not change the R.ax for sarafotoxin S6b but increased its potency in both hypoxic and oxygenated tissues. 4. In hypoxia, and in the presence of both the endothelium and 100 microM L-
NAME
, the Rmax for
endothelin-1
was 1.6 times greater than that in hypoxia in the absence of L-
NAME
. Co-infusion of 100 microM L-arginine, but not of 100 mircoM D-arginine, with 100 microM L-
NAME
reversed this effect. The presence of L-
NAME
decreased the potency of
endothelin-1
. 5. Destroying the endothelium did not affect the Rmax for noradrenaline in either oxygenated conditions or hypoxia. Changing 02 tension when the endothelium was intact had no effect on the Rmax but it was 11% greater in oxygenated, than in hypoxic, endothelium denuded preparations. Endothelial destruction decreased the potency of noradrenaline in hypoxia but increased it in oxygenated tissues. In hypoxia, L-
NAME
had no effect on the ED50 relative to control preparations with endothelium but the Rmax was 30% greater. 6. 5-Hydroxytryptamine gave very small pressor responses in the presence of endothelium in both oxygenated and hypoxic tissues but the Rmax was 1.7 times greater in hypoxia. L-
NAME
increased the R,,x by 9.8 times in oxygenated preparations and 6.3 fold in hypoxia. The ED5o values were the same in all conditions. 7. It is concluded that, although hypoxia generally increased the R.. for the endothelin/sarafotoxin peptides, the changes could not be explained by a simple increase in receptor number since hypoxia decreased the potency of endothelin-3 and sarafotoxin S6b. Thus alterations in receptor binding or activation properties, or both, also occurred. The changes associated with hypoxia were not common to all vasoconstrictor agonists since, in the absence of endothelial function, hypoxia did not affect the Rmax values for either noradrenaline or 5-hydroxytryptamine. Also, the pressor responses to the peptides and both the amines can be modulated by the endothelium in hypoxia as well as in oxygenated conditions.
...
PMID:Endothelial modulation and changes in endothelin pressor activity during hypoxia in the rat isolated perfused superior mesenteric arterial bed. 188 99
1. Conscious Long Evans rats, chronically instrumented for cardiovascular measurements, were challenged with i.v. bolus doses of glyceryl trinitrate (40 nmol kg-1), acetylcholine (1.2 nmol kg-1), bradykinin (3.2 nmol kg-1), or
endothelin-1
(0.25 nmol kg-1). Under control conditions these doses produced similar falls in mean arterial blood pressure (glyceryl trinitrate, -20 +/- 3 mmHg; acetylcholine, -24 +/- 2 mmHg: bradykinin, -21 +/- 3 mmHg;
endothelin-1
, -25 +/- 3 mmHg), associated with renal, mesenteric and hindquarters vasodilatations (except for
endothelin-1
which caused mesenteric vasoconstriction). 2. In the presence of NG-nitro-L-arginine methyl ester (L-
NAME
, 10 mgkg-1), a potent inhibitor of nitric oxide biosynthesis and endothelium-dependent vasorelaxation in vitro, the hypotensive responses to glyceryl trinitrate, acetylcholine, and
endothelin-1
were increased, although that to bradykinin was not. However, comparing the differences between the response to glyceryl trinitrate and that to any other agonist in the absence and presence of L-
NAME
showed that there were relative attenuations of the hypotensive responses to bradykinin and
endothelin-1
, but not to acetylcholine, in the presence of L-
NAME
. 3. This comparative analysis showed that the renal and hindquarters vasodilator responses to bradykinin and
endothelin-1
were attenuated in the presence of L-
NAME
, but the renal, mesenteric and hindquarters vasodilator responses to acetylcholine were not. However, when L-
NAME
was administered in the presence of pentolinium, captopril and the vasopressin V1-receptor antagonist, d(CH2)5[Tyr-(Et)]DAVP, (to abolish baroreflex and neurohumoral mechanisms), there was attenuation of the renal and mesenteric vasodilator effects of acetylcholine relative to those seen with glyceryl trinitrate. Under those conditions only the renal vasodilator effects of bradykinin and
endothelin-1
were attenuated. 4. In separate experiments in conscious Long Evans rats, direct measurement of cardiac haemodynamics showed that the hypotensive responses to glyceryl trinitrate, acetylcholine, bradykinin and endothelin-l were entirely attributable to rises in total peripheral conductance since both in the absence and presence of L-
NAME
there were no reductions in cardiac index in response to these substances. 5. The results indicate that measurement of systemic arterial blood pressure alone in conscious rats does not permit reliable quantitation of the influence of L-
NAME
on regional vasodilator responses to glyceryl trinitrate, acetylcholine, bradykinin or
endothelin-1
. Furthermore, these substances exert effects in different vascular beds that may be differentially influenced by baroreflex mechanisms, neurohumoral mechanisms, or both. Moreover, except in the case of the renal vasodilator response to
endothelin-1
(which was abolished in the presence of L-
NAME
), even when L-
NAME
caused attenuation of the vasodilator effects of acetylcholine or bradykinin (relative to glyceryl trinitrate), substantial responses remained. It is feasible that such responses in vivo are nitric oxide-independent.
...
PMID:Regional and cardiac haemodynamic responses to glyceryl trinitrate, acetylcholine, bradykinin and endothelin-1 in conscious rats: effects of NG-nitro-L-arginine methyl ester. 212 52
The injection of
endothelin-1
(
ET-1
) into the dorsolateral periaqueductal gray (PAG) area of freely moving rats at doses from 0.1 to 1 pmol/rat induced rotation along the long axis of the body (barrel-rolling). The pretreatment of this area with L-
NAME
(N omega-nitro-L-arginine methyl ester, 1 mumol/rat), an L-arginine analogue and a potent inhibitor of nitric oxide (NO) biosynthesis, significantly (p < 0.01) potentiated the duration of the
ET-1
-induced barrel-rolling. Pretreatment of the PAG area with L-arginine (1 mumol/rat), a precursor of NO, significantly (p < 0.01) decreased the
ET-1
-induced effects. These preliminary data indicate that the L-arginine-NO pathway exerts a functional antagonism on
ET-1
induced barrel-rolling at the level of the PAG area.
...
PMID:Effects of L-name on endothelin-1-induced barrel-rolling in periaqueductal gray area of rats. 747 48
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