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

The mechanisms and myocardial alterations associated with NO-deficient hypertension are still far from clear. The aim of the present study was to focus on the enzyme histochemical and subcellular changes in the heart of L-NAME treated rats, as well as to examine the influence of captopril treatment. Wistar rats were administered either L-NAME (40 mg/kg/day) alone or together with captopril (100 mg/kg/day) for a period of 4 weeks. A significant increase of blood pressure confirmed the reliability of the model. The results showed that long-lasting L-NAME administration was accompanied by a decrease of endothelial NO-synthase activity and by a significant local decrease of the following enzyme activities: capillary-related alkaline phosphatase, 5'-nucleotidase and ATPase (but not dipeptidyl peptidase IV) and cardiomyocyte-related glycogen phosphorylase, succinic dehydrogenase, beta-hydroxybutyrate dehydrogenase and ATPases. No activity of these enzymes was found in the scar, whereas a marked increase of alkaline phosphatase and dipeptidyl peptidase IV activities was found in the foci of fibrotization. Histochemical changes correlated with subcellular changes, which were characterized by 1) apparent fibroblast activation associated with interstitial/perivascular fibrosis, 2) heterogeneous population of the normal, hypertrophic and injured cardiomyocytes, 3) enhancement of the atrial granules and their translocation into the sarcolemma, and 4) impairment of capillaries as well as by induction of angiogenesis. Similar alterations were also found in the heart of captopril co-treated rats, despite of the significant suppression of blood pressure. The results indicate that NO-deficient hypertension is accompanied by metabolic disturbances and ultrastructural alterations of the heart and these changes are probably not induced by the renin-angiotension system only.
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PMID:Chronic disturbances in NO production results in histochemical and subcellular alterations of the rat heart. 1080 8

1. In rat isolated renal artery segments contracted with 0.1 microM phenylephrine and in the presence of the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME), carbachol and acetylcholine produced endothelium-dependent relaxations. The mechanisms underlying these relaxations were studied. 2. These relaxations were not affected by ODQ (1H-[1,2,4]oxadiazolo[4,3, -a]quinoxalin-1-one) or indomethacin. In arteries contracted with 20 - 30 mM K(+), L-NAME-resistant relaxations induced by carbachol and acetylcholine were virtually absent. 3. The Na(+)-K(+) ATPase inhibitor ouabain reduced these relaxations in a concentration-dependent manner. 4. In K(+)-free media, addition of K(+) (5 mM) produced 90. 5+/-3.9% (n=3) relaxation of phenylephrine-induced tone. This relaxation was endothelium-independent and ouabain-sensitive. 5. Tetraethylammonium (TEA), charybdotoxin (ChTX) and iberiotoxin (IbTX) reduced the sensitivity of carbachol-induced relaxations, but did not change the maximal response. These relaxations were not altered by 4-aminopyridine (4-AP), glibenclamide or apamin. Acetylcholine (1 microM)-induced relaxation was reduced by ChTX, but not by TEA or IbTX. 6. The cytochrome P450 inhibitor miconazole, but not 17-octadecynoic acid, reduced the sensitivity of carbachol-induced relaxations, without changing the maximal response. 7. In conclusion, in rat isolated renal arteries, acetylcholine and carbachol produced a non-NO/non-PGI(2) relaxation which is mediated by an endothelium-derived hyperpolarizing factor (EDHF). This factor does not appear to be a cytochrome P450 metabolite. The inhibition by ouabain of these relaxations suggests the possible involvement of Na(+)-K(+) ATPase activation in EDHF responses, although other mechanisms cannot be totally ruled out.
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PMID:Mechanisms of nitric oxide-independent relaxations induced by carbachol and acetylcholine in rat isolated renal arteries. 1090 55

Vascular smooth muscle is thought to possess an H+-K+ ATPase that contributes to the regulation of intracellular K+ concentration and pH. We have examined the effect of the H+, K+-ATPase inhibitor SCH 28080 on vascular smooth muscle tone in guinea-pig and human isolated arteries, and on 86Rb+ uptake in cultured guinea-pig aortic smooth muscle cells. SCH 28080 (0.1-300 microM) produced relaxation of isolated guinea-pig aorta, guinea-pig pulmonary artery and human pulmonary artery. Relaxation occurred in tissues pre-contracted with phenylephrine, histamine or the thromboxane mimetic U44069. Relaxation. was reversible, and was not affected by tetrodotoxin, indomethacin, nordihydroguiaretic acid (NDGA), 1-aminobenzotriazole (1-ABT), N(G)-nitro-L-arginine methyl ester (L-NAME), removal of the endothelium or removal of extracellular K+. SCH 28080 had no effect on 86Rb+ uptake in cultured guinea-pig aortic smooth muscle cells. In conclusion, SCH 28080 relaxes vascular smooth muscle at concentrations known to inhibit the H+-K+ ATPase. The persistence of relaxation in a K+-free medium and the failure of SCH 28080 to inhibit 86Rb+ uptake suggest that relaxation may be unrelated to H+, K+-ATPase inhibition, and indicate that this agent may not be considered as a selective H+, K+-ATPase inhibitor in vascular preparations.
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PMID:Inhibition of vascular smooth muscle tone by the H+, K+-ATPase inhibitor SCH 28080. 1093 37

A non-phorbol ester-type tumor promoter, thapsigargin has been reported to deplete Ca(2+) stores in endothelial cells by inhibiting Ca(2+)-ATPase, which in turn increases intracellular Ca(2+) by mobilization of extracellular Ca(2+), leading to activation of constitutive nitric oxide synthase (cNOS) and resultant generation of nitric oxide (NO). In the present study, to evaluate the role of Ca(2+) in the release of epithelium-dependent relaxing factor (EpDRF), we determined the effect of thapsigargin (10(-6) M) on the contraction evoked by exogenous Ca(2+) or acetylcholine (10(-5) M) in epithelium-denuded or epithelium-intact smooth muscle from guinea pig trachea. The following results were obtained: (1) In epithelium-denuded smooth muscle, the contraction evoked by exogenous Ca(2+) in Ca(2+)-free solution or by acetylcholine (10(-5) M) in Ca(2+)-containing solution did not change within 20 min after thapsigargin application, but the contraction evoked by exogenous Ca(2+) increased markedly after 120 min, indicating that thapsigargin had no effect on smooth muscle itself within 20 min of application. The following experiments were performed within 20 min of thapsigargin application. (2) In epithelium-intact smooth muscle, thapsigargin significantly suppressed the contraction evoked by acetylcholine, suggesting that thapsigargin stimulate the epithelium to produce EpDRF. N(G)-nitro-L-arginine methylester (L-NAME) partly, but significantly, attenuated this inhibitory effect of thapsigargin. (3) In epithelium-denuded smooth muscle, atropine (10(-6) M) and L-NAME (10(-5) M) did not change the contraction evoked by exogenous Ca(2+) after application of thapsigargin, suggesting that thapsigargin did not stimulate acetylcholine and NO release from nerve terminals. These results suggest that thapsigargin (10(-6) M) may stimulate EpDRF, including NO and other factor(s) by Ca(2+)-dependent mechanisms.
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PMID:Thapsigargin, a Ca(2+)-ATPase inhibitor, relaxes guinea pig tracheal smooth muscle by producing epithelium-dependent relaxing factors. 1113 57

1. Bradykinin (BK) effect on the [Ca(2+)](i) response to 1 nM angiotensin II was examined in muscular juxtamedullary efferent arterioles (EA) of rat kidney. 2. BK (10 nM) applied during the angiotensin II-stimulated [Ca(2+)](i) increase, induced a [Ca(2+)](i) drop (73+/-2%). This drop was prevented by de-endothelialization and suppressed by HOE 140, a B2 receptor antagonist. It was neither affected by L-NAME or indomethacin, nor mimicked by sodium nitroprusside, 8-bromo-cyclic GMP or PGI(2). The BK effect did not occur when the [Ca(2+)](i) increase was caused by 100 mM KCl-induced membrane depolarization and was abolished by 0.1 microM charybdotoxin, a K(+) channel blocker. 3. Although proadifen prevented the BK-caused [Ca(2+)](i) fall, more selective cytochrome P450 inhibitors, 17-octadecynoic acid (50 microM) and 7-ethoxyresorufin (10 microM) were without effect. 4. Increasing extracellular potassium from 5 to 15 mM during angiotensin II stimulation caused a [Ca(2+)](i) decrease (26+/-4%) smaller than BK which was charybdotoxin-insensitive. Inhibition of inward rectifying K(+) channels by 30 microM BaCl(2) and/or of Na(+)/K(+) ATPase by 1 mM ouabain abolished the [Ca(2+)](i) decrease elicited by potassium but not by BK. 5. A voltage-operated calcium channel blocker, nifedipine (1 microM) did not prevent the BK effect but reduced the [Ca(2+)](i) drop. 6. These results indicate that the BK-induced [Ca(2+)](i) decrease in angiotensin II-stimulated muscular EA is mediated by an EDHF which activates charybdotoxin-sensitive K(+) channels. In these vessels, EDHF seems to be neither a cytochrome P450-derived arachidonic acid metabolite nor K(+) itself. The closure of voltage-operated calcium channels is not the only cellular mechanism involved in this EDHF-mediated [Ca(2+)](i) decrease.
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PMID:Bradykinin attenuates the [Ca(2+)](i) response to angiotensin II of renal juxtamedullary efferent arterioles via an EDHF. 1115 28

The present experiments were designed to investigate the effects of omeprazole, a H(+)-K+ ATPase inhibitor, on corporal smooth muscle tone in vitro. All spontaneous contractile activity in the corpus cavernosum was blocked following omeprazole (0.1 mM-1 mM) administration. However atropine (1 microM), Nw-nitro L-arginine methyl ester (L-NAME, 30 microM) or indomethacin (10 microM) did not affect the spontaneous contraction. Omeprazole (10 microM-1 mM) concentration-dependently induced relaxation in corporal smooth muscle precontracted with 10 microM phenylephrine or 80 mM KCl. Pretreatment of corporal tissue with L-NAME (30 microM), indomethacin (10 microM), ammonium chloride (7.5 mM), sodium acetate (7.5 mM), tetraethyl ammonium chloride (0.5 mM) or glibenclamide (1 microM) had no effect on the omeprazole induced relaxant responses. Nimodipine, an L-type Ca++ channel blocker, relaxed corporal strips precontracted with 80 mM KCl. Collectively, these results indicate that the inhibition of spontaneous contraction and the relaxation of precontracted corporal smooth muscle by omeprazole is probably mediated by the blockade of calcium channels. Further work is needed to determine the cellular mechanism(s) of action by which omeprazole acts on corpus cavernosum smooth muscle.
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PMID:Evidence of relaxant effect of omeprazole in rabbit corpus cavernosum in vitro. 1121 Jul 16

The inhibition of high-affinity isoforms of the Na+,K+-ATPase by nanomolar levels of ouabain has been proposed to enhance the actions of vasoconstrictor agents that act via a Ca+2-dependent mechanism. The present study tested this hypothesis by evaluating the effects of ouabain (6 and 18 microg/kg, i.v.) on the vasopressor actions of phenylephrine and norepinephrine in anesthetized, reflex-blocked rats. In separate groups of animals, dose-response curves for increases in diastolic pressure produced by phenylephrine were generated after the administration of saline (control), ouabain (18 microg/kg), L-omega-N-nitro arginine methyl ester (L-NAME, 3 micromol/kg) and angiotensin II (15 ng/kg per min). Treatment with ouabain (18 microg/kg) produced an increase in diastolic pressure of 19+/-3 mm Hg but did not significantly alter the potency or maximal response produced by phenylephrine. In contrast, treatment with angiotensin II and L-NAME, agents known to enhance the actions of alpha-adrenoceptor agonists, increased the potency of phenylephrine. In animals in which the pressor actions of norepinephrine were evaluated before and after the administration of ouabain (6 microg/kg), ouabain did not alter the pressor response to norepinephrine. Blockade of alpha-adrenoceptors with phentolamine was found to attenuate as well as partially reverse the increase in diastolic pressure produced by ouabain. These observations suggest that ouabain produces a pressor response by actions on sympathetic nerve endings as well as on vascular smooth muscle and that these actions do not alter the sensitivity to phenylephrine or norepinephrine.
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PMID:Acute pressor actions of ouabain do not enhance the actions of phenylephrine or norepinephrine in anesthetized rats. 1124 25

In the present study we investigated the effect of acute administration of L-arginine on Na(+),K(+)-ATPase and Mg(2+)-ATPase activities and on some parameters of oxidative stress (chemiluminescence and total radical-trapping antioxidant parameter-TRAP) in midbrain of adult rats. We also tested the effect of L-NAME on the effects produced by arginine. Sixty-day-old rats were treated with an acute intraperitoneal injection of saline (group I, control), arginine (0.8 g/kg) (group II), L-NAME (2 mg/kg) (group III) or arginine (0.8 g/kg) plus L-NAME (2 mg/kg) (group IV). Na(+),K(+)-ATPase activity was significantly reduced in the arginine-treated rats, but was not affected by other treatments. In contrast, Mg(2+)-ATPase activity was not altered by any treatment. Furthermore, chemiluminescence was significantly increased and TRAP was significantly decreased in arginine-treated rats, whereas the simultaneous injection of L-NAME prevented these effects. These results demonstrate that in vivo arginine administration reduces Na(+),K(+)-ATPase activity possibly through free radical generation induced by NO formation.
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PMID:Nitric oxide synthase inhibition by L-NAME prevents the decrease of Na+,K+-ATPase activity in midbrain of rats subjected to arginine administration. 1151 78

The renal microvascular actions of ACh were investigated using the in vitro perfused hydronephrotic rat kidney. ACh reversed ANG II-induced vasoconstriction in the afferent and efferent arteriole by 106 +/- 2 and 75 +/- 5%, respectively. Inhibition of nitric oxide synthase [NOS; 100 micromol/l N(G)-nitro-L-arginine methyl ester (L-NAME)] and cyclooxygenase (COX; 10 micromol/l ibuprofen) prevented the sustained response of the afferent arteriole but did not reduce the magnitude of the initial dilation (97 +/- 7%). However, NOS/COX inhibition abolished the response of the efferent arteriole. The underlying mechanisms mediating this endothelium-derived hyperpolarizing factor (EDHF)-like response were characterized using K channel blockers. Ba (100 micromol/l), tetraethylammonium (1 mmol/l), and ouabain (3 mmol/l) had no effect, arguing against a role of an inward rectifier K channel, large-conductance Ca-activated K channel, or Na,K-ATPase. Charybdotoxin (10 nmol/l) and apamin (1.0micromol/l) attenuated the response when administered alone (63 +/- 7% and 37 +/- 5%, respectively) and abolished the response when coadministered (0.1 +/- 1.0%). These findings indicate that, as in other vascular beds, the renal EDHF-like response to ACh involves K channels that are sensitive to a combination of apamin and charybdotoxin. Our finding that EDHF modulates preglomerular, but not postglomerular, tone is consistent with the evolving concept that vasomotor mechanisms in cortical efferent arterioles do not involve voltage-gated Ca entry.
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PMID:Determinants of renal microvascular response to ACh: afferent and efferent arteriolar actions of EDHF. 1173 20

We evaluated the anti-inflammatory and neuroprotective effect of nonselective NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), in experimental bacterial meningitis in the newborn piglet. Meningitis was induced by intracisternal injection of 10(8) colony forming units of Escherichia coli. L-NAME 10 mg kg(-1) was given intravenously 30 min before induction of meningitis. L-NAME significantly attenuated the increase in intracranial pressure and decrease in cerebrospinal fluid glucose concentration observed in the meningitis group. Systemic and cerebral perfusion pressure were even higher compared to the control and meningitis groups. However, the meningitis-induced increase in tumor necrosis factor-alpha level, leukocyte numbers and lactate level in the cerebrospinal fluid was not significantly attenuated with L-NAME administration. Reduced cerebral cortical cell membrane Na+, K+ -ATPase activity and increased lipid peroxidation products, indicative of meningitis-induced brain cell membrane dysfunction, were significantly improved with L-NAME treatment. Decreased brain glucose and ATP levels were also significantly improved with L-NAME treatment. These findings suggest that L-NAME was effective in attenuating the acute inflammatory responses and brain injury in neonatal bacterial meningitis.
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PMID:N(omega) -nitro-L-arginine methyl ester (L-NAME) attenuates the acute inflammatory responses and brain injury during the early phase of experimental Escherichia coli meningitis in the newborn piglet. 1176 Aug 79


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