Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was carried out to evaluate the relaxation induced by histamine in tail arteries of rats after chronic inhibition of nitric oxide (NO) synthesis with the inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) compared to tail arteries of control rats. The maximum relaxation induced by histamine was greater in control (88.09% +/-5.50, n=6) than in L-NAME arteries (47.33% +/-6.40, n=6), although pD(2) values were not different between the two groups (control: 4.89+/-0.08; L-NAME: 4.81+/-0.10). After incubation with 100 microM L-NAME in vitro, the maximum relaxation induced by histamine was only reduced in the control arteries (44.93% +/-2.35, n=6), whereas it had no effect on aortas of rats pretreated with this inhibitor. The incubation with 100 microM L-NAME had the same effect as endothelium removal in both arterial groups. Furthermore, the relaxation induced by histamine was unaffected by indomethacin. The combination of L-NAME and the histamine antagonist cimetidine completely abolished the relaxation induced by histamine in both arterial groups. These results show that when NO synthesis is impaired, the relaxation induced by histamine is endothelium independent, and when NO-synthase is active, the relaxation involves both NO released from endothelial cells and an endothelium-independent mechanism that is sensitive to cimetidine.
Gen Pharmacol 2000 Jun
PMID:Relaxation induced by histamine is not endothelium dependent in tail arteries of L-NAME-treated rats. 1148 93

KMCP-98 is a newly synthesized adenosine receptor agonist by alkylation at the 7-position of the xanthines nucleus. We first investigated the pharmacological activities of KMCP-98 under in vivo and in vitro conditions. Acute intravenous injection of KMCP-98 (1.0, 2.0 and 3.0 mg/kg) produced a temporary fall in blood pressure and heart rate, followed by a sustained fall in heart rate in pentobarbital-anesthetized Wistar rats. The hypotensive and bradycardiac responses were inhibited by pretreatment with an A(1) adenosine receptor antagonist 8-phenyltheophylline (8-PT, 0.5 mg/kg). Both KMCP-98 and adenosine (0.3-100 microM) produced negative inotropic activity in isolated guinea pig left atria. The negative inotropic activity of KMCP-98 was significantly blocked by pretreatment with A(1) receptor antagonists 8-PT (10 microM) and xanthine amine congener (XAC, 10 microM), a nonselective adenosine antagonist theophylline (10 microM), a K(+) channel blocker tetraethylammonium (TEA, 10 mM) and a K(ATP) channel blocker glibenclamide (1 microM). KMCP-98 (0.03-30 microM) produced concentration-dependent relaxations in carbachol (1 microM) precontracted guinea pig tracheal smooth muscle. The trachea relaxant response of KMCP-98 was markedly inhibited by A(2), A(2a) and A(2b) adenosine receptor antagonists 3,7-dimethyl-1-propargylxanthine (DMPX, 10 microM), 8-(3-chlorostyryl)caffeine (CSC, 10 microM) and alloxazine (10 microM), respectively, the nitric oxide synthase (NOS) inhibitor L-NAME (100 microM) and also by TEA and glibenclamide. In addition, KMCP-98 (0.03-30 microM) elicited relaxant response in norepinephrine (3 microM) precontracted rat thoracic aorta in a concentration-dependent manner. The thoracic aorta relaxant response of KMCP-98 was also significantly inhibited by DMPX, CSC, alloxazine, L-NAME, TEA and glibenclamide. Furthermore, the binding characteristics of KMCP-98, adenosine and 5'-N-ethylcarboxaminoadenosine (NECA) were evaluated in [(3)H]DPCPX and [(3)H]CGS 21680 binding to rat cortex and striatum, respectively. The K(i) values of KMCP-98 for predominate A(1) and A(2) adenosine receptor sites were 3908+/-952 and 158+/-10 nM, respectively. In conclusion, KMCP-98 was found to be a xanthine-based adenosine receptor agonist associated cardiac depression, tracheal and aortic smooth muscle relaxations.
Gen Pharmacol 2000 Jul
PMID:A unique xanthine derivative KMCP-98 with activation of adenosine receptor subtypes. 1167 5

The change of blood pressure and heart rate after intravenous injection of Korea red ginseng (KRG) were studied in the conscious normotensive and one-kidney, one-clip Goldblatt hypertensive (1K, 1C-GBH) rats. Crude saponin (CS) of KRG (50, 100 mg/kg i.v.) induced a hypotensive effect and bradycardia in a dose-dependent manner in the anesthetized rats. On the other hand, CS of KRG (100 mg/kg) induced a hypotensive effect and reflex tachycardia in the conscious rats. Saponin-free fraction (SFF) of KRG did not affect them in the anesthetized normotensive rats (P>.05). The maximal hypotensive effect by CS of KRG in the conscious 1K, 1C-GBH hypertensive rats and L-nitroarginine methyl ester (L-NAME, 40 mg/kg)-treated conscious hypertensive rats was not different from that of conscious normotensive rats (Delta 31.6+/-6.3, Delta 27.5+/-5.8 vs. Delta 26.7+/-4.3 mmHg, P>.05). However, pretreatment of L-NAME significantly inhibited the reflex tachycardia by CS of KRG (70.8+/-7.0 vs. 30.6+/-15.0 bpm, P<.05). Hemolysate-sensitive nitric oxide (NO) current by the CS of KRG was greater than that of the SFF of KRG (651.9+/-128.2 pA for CS and 164.9+/-92.5 pA for SFF, P<.001). These findings suggest that KRG has a hypotensive effect and its effect may be due to saponin fraction of KRG in the conscious rats. The releasing effect of NO of KRG, like NO donor, may be partly contributed to the hypotensive effect of KRG.
Gen Pharmacol 2000 Sep
PMID:Effect of Korea red ginseng on the blood pressure in conscious hypertensive rats. 1174 35

We examined the role of endothelium-derived relaxing factors nitric oxide (NO), endothelium-derived hyperpolarising factor (EDHF), and prostaglandins (PGs) to P(2Y1)- and P(2Y2)-purinoceptor-induced vasodilation in isolated rat kidney. To do it, we analysed the renal response to ATP, 2-methylthio ATP, and UTP in rat renal vasculature under normal conditions and after the administration of: N(w)-nitro-L-arginine (L-NAME), increased K(+) concentration, indomethacin, and L-NAME and increased K(+) together. Our results indicate that the vasodilator response to P(2Y1)- and P(2Y2)-purinoceptor activation in the isolated perfused kidney of rats is subserved by EDHF and NO.
Gen Pharmacol 2000 Sep
PMID:Contribution of endothelium-derived relaxing factors to P2Y-purinoceptor-induced vasodilation in the isolated rat kidney. 1174 34

Experiments were undertaken to determine if nitric oxide (NO) plays a role in regulation of basal blood flow in the oral cavity of pentobarbital anesthetized cats and, if so, to quantify this effect using dose-response relationships. Blood flow was continuously measured from the surface of the tongue and mandibular gingiva (laser-Doppler flowmetry) and from the lingual artery (ultrasonic flowmetry). Cardiovascular parameters also were recorded. Administration of the nonselective inhibitor of nitric oxide synthase (NOS), L-NAME (0.08-20 mg/kg i.v.), produced a dose-related increase of blood pressure associated with decreases of blood flow at all three measurement sites. Maximal blood flow depression of 50-60% was seen 30-60 min after administration of 1.25 mg/kg of L-NAME. D-NAME (1.25 mg/kg i.v.) was inactive at all sites. Subsequent administration of L-arginine partially reversed effects of L-NAME in the lingual artery and tongue, but not in the gingival circulation. The neuronally selective NOS inhibitor, 7-nitroindazole (7-NI, 30 mg/kg i.p.), was devoid of effect on any of the measured parameters. These results suggest that endothelial (but not neuronally derived) NO plays an important role in control of basal blood flow in oral tissues of the cat.
Gen Pharmacol 2000 Sep
PMID:Role of nitric oxide in maintenance of basal oral tissue blood flow in anesthetized cats. 1174 38

The present study further examined the functional presence and the signal transduction mechanism(s) for adenosine A(2A) and A(2B) receptors through nitric oxide (NO) and the guanosine 3', 5'-cyclic monophosphate (cGMP) pathway in cultured porcine coronary artery endothelial cells (PCAEC). The application of adenosine receptor agonists, NECA, CGS-21680 and CAD between 10(-7) and 10(-4) M, enhanced the production of NO (measured as nitrite) in a dose-dependent manner. On the basis of EC(50) values, these agonists showed the following order of potency: NECA>CGS-21680>CAD. This order appears to be of the A(2) adenosine receptor subtype. Similarly, the same concentrations of adenosine agonists evoked the production of cGMP in a dose-dependent manner, exhibiting a rank order that is similar to that of NO production. NO synthase inhibitor, N-nitro-L-arginine methylester (L-NAME, 10(-5) M), inhibited the production of NO and cGMP, which was reversed by L-arginine (10(-4) M). Selective A(2A) adenosine receptor antagonists, ZM-241385 and SCH-58261, at 10(-7) M, significantly inhibited the effects of CGS-21680, but only partly inhibited the effect of NECA on NO and cGMP production. Along with the earlier molecular evidence from this laboratory [Am. J. Physiol. 279 (2000) H650], the present data further support the presence of both A(2A) and A(2B) receptors in PCAEC. These results further support that coronary endothelial cells express functional A(2A) and A(2B) adenosine receptors, leading to GMP production through the NO-synthase-linked mechanism. This is the first direct evidence where an A(2B) adenosine receptor has been linked to NO production in cultured endothelial cells and could play a role in coronary artery physiology and pathophysiology.
Gen Pharmacol 2000 Sep
PMID:Adenosine A(2A) and A(2B) receptors mediated nitric oxide production in coronary artery endothelial cells. 1174 40

We have shown previously that raising extracellular Ca(2)+ inhibited the apical 70-pS K channel in the thick ascending limb (TAL; Wang, W.H., M. Lu, and S.C. Hebert. 1996. Am. J. Physiol. 270:C103-C111). We now used the patch-clamp technique to study the effect of increasing the extracellular Ca(2)+ on the 70-pS K channel in the mTAL from rats on a different K diet. Increasing the extracellular Ca(2)+ from 10 microM to 0.5, 1, and to 1.5 mM in the mTAL from rats on a K-deficient (KD) diet inhibited the channel activity by 30, 65, and 90%, respectively. In contrast, raising the extracellular Ca(2)+ to 1.5 mM had no significant effect on channel activity in the mTAL from animals on a high K (HK) diet and further increasing the extracellular Ca(2)+ to 2.5, 3.5, and 5.5 mM decreased the channel activity by 29, 55, and 90%, respectively. Inhibition of the cytochrome P450 monooxygenase completely abolished the effect of the extracellular Ca(2)+ on channel activity in the mTAL from rats on a different K diet. In contrast, blocking cyclooxygenase did not significantly alter the responsiveness of the 70-pS K channel to the extracellular Ca(2)+. Moreover, addition of sodium nitropruside, a nitric oxide (NO) donor, not only increased the channel activity, but also blunted the inhibitory effect of the extracellular Ca(2)+ on the 70-pS K channel and decreased 20-hydroxyeicosatetraenoic acid (20-HETE) concentration in the mTAL from rats on a KD diet. In contrast, inhibiting NOS with L-NAME enhanced the inhibitory effect of the extracellular Ca(2)+ on the channel activity and increased 20-HETE concentration in the mTAL from rats on a high K diet. Western blot has further shown that the expression of inducible NO synthase (iNOS) is significantly higher in the renal medulla from rats on an HK diet than that on a KD diet. Also, addition of S-nitroso-N-acetylpenicillamine abolished the inhibitory effect of arachidonic acid on channel activity in the mTAL, whereas it did not block the inhibitory effect of 20-HETE. We conclude that a low dietary K intake increases the sensitivity of the 70-pS K channel to the extracellular Ca(2)+, and that a decrease in NOS activity is involved in enhancing the inhibitory effect of the extracellular Ca(2)+ on channel activity in the mTAL during K depletion.
J Gen Physiol 2002 Jan
PMID:K depletion enhances the extracellular Ca2+-induced inhibition of the apical K channels in the mTAL of rat kidney. 1177 36

The responses to endothelial vasodilators and exogenous nitric oxide (NO) were characterized in intact isolated uterine vascular beds of nonpregnant, midpregnant and late-pregnant rats perfused with Kreb's buffer (37 degrees C, 5% CO(2) in air, pH approximately 7.4) containing 2% dextran and indomethacin. Phenylephrine increased perfusion pressure in the vascular beds equally in all three groups. In the presence of phenylephrine, N(omega)-nitro-L-arginine methyl ester (L-NAME) significantly augmented perfusion pressure in the order: nonpregnant<midpregnant<late-pregnant uterine vascular bed. Acetylcholine and bradykinin-induced attenuation of perfusion pressure did not depend on gestational age. The decrease in perfusion pressure induced by acetylcholine was nonsignificantly attenuated by L-NAME in vascular beds from pregnant rats. The attenuation induced by bradykinin reached significant level in the vascular beds from midpregnant rats. The diethylamine (DEA)/NO-induced decrease in perfusion pressure was not influenced by L-NAME in any group. These data demonstrate the augmentation of basal release of NO associated with progression of pregnancy, while the responses to endothelial vasodilators do not depend on gestational age and are not abolished by inhibition of NO synthase, suggesting involvement of nonprostanoid non-NO factor in the control of uterine circulation.
Gen Pharmacol 2000 Dec
PMID:Responses of isolated perfused uterine vascular beds of nonpregnant and pregnant rats to endogenous and exogenous nitric oxide. 1192 59

(a) We studied basal endothelial function in the insulin-resistant, obese Zucker rat, including the influence of superoxide anion on the regulation of contractile reactivity by nitric oxide (NO), following treatment in vivo with the antioxidant tiron or the pro-oxidant combination hydroquinone+buthionine sulfoximine. (b) The leftward shift in the contractile potency of phenylephrine due to NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) was greater in the isolated aorta of the obese Zucker rat relative to its insulin-sensitive littermate, the lean Zucker rat. (c) Pretreatment with tiron depressed vasoconstriction to phenylephrine and comparably enhanced the L-NAME-mediated leftward shift in contractile reactivity in the obese and lean Zucker rats in hydroquinone+buthionine sulfoximine-sensitive manner. (d) Our data therefore indicate superior endothelial function in the obese relative to the lean Zucker rat, reflected by a greater regulation of vasoconstrictor reactivity by basal NO, while the regulation of NO bioavailability by superoxide anion is similar.
Gen Pharmacol 2000 Dec
PMID:Investigation of basal endothelial function in the obese Zucker rat in vitro. 1192 60

This study was designed to determine whether the relaxant effect of apigenin was endothelium dependent and to examine the possible antiproliferative effect of apigenin. Apigenin relaxed the phenylephrine-precontracted endothelium-intact aortic rings with IC(50) value of 3.7+/-0.5 microM and removal of a functional endothelium significantly attenuated this relaxation (IC(50)=8.2+/-0.9 microM). However, apigenin did not affect the 0.1 microM phorbol 12,13-dibutyrate-induced contraction (IC(50)=34.6+/-1.2 microM) within the concentration range that relaxed the phenylephrine-contracted arteries, suggesting that apigenin did not influence protein kinase C-mediated contractile mechanisms in rat aorta. Pretreatment of apigenin significantly potentiated the relaxant effect of acetylcholine on phenylephrine-induced contraction. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) or methylene blue reduced the relaxant effect of apigenin. Apigenin (10 microM) increased the guanosine 3',5'-cyclic monophosphate (cGMP) content of endothelium-intact tissues. Pretreatment with L-NAME (100 microM) or removal of endothelium significantly suppressed the effect of apigenin on cGMP production. In addition, apigenin significantly inhibited [3H]thymidine incorporation into DNA of primary cultured rat aortic smooth muscle cell in a dose-dependent manner. These findings suggest that besides influx and release of Ca(2+), nitric oxide (NO) and cGMP may account for the apigenin-induced endothelium-dependent relaxation and hypotensive activity. Both vasorelaxant and antiproliferative activities may contribute to a benefit of apigenin in the vascular system.
Gen Pharmacol 2000 Dec
PMID:Endothelium-dependent vasorelaxant and antiproliferative effects of apigenin. 1192 65


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