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. Membrane potential and tension were measured simultaneously in ring segments of main coronary artery of guinea-pigs. The synthetic thromboxane A2 analogue U46619 depolarized the tissues from -58 +/- 2 to -40 +/- 1 mV and increased tension by 12 +/- 1 mN mm-1. Nitric oxide (NO) and Iloprost, the stable analogue of prostacyclin, evoked hyperpolarization and relaxation. 2. The concentration of NO required to evoke half-maximal hyperpolarization (EC50 of 2 x 10(-5) M) was 40-fold higher than that which was required to induce relaxation (EC50 of 5 x 10(-7) M). The EC50 for Iloprost-induced hyperpolarization (3 x 10(-8) M) was similar to that for relaxation (4 x 10(-8) M). 3. Glibenclamide (10(-6) M) abolished the hyperpolarization in response to both NO and Iloprost but was without effect on the amplitudes of the relaxations over the complete concentration-response curves. 4. Acetylcholine evoked concentration-dependent hyperpolarization and relaxation in the presence of N omega-nitro-L-arginine methyl ester (NAME; 10(-5) M) and indomethacin (10(-6) M), and these responses were attributed to endothelium-derived hyperpolarizing factor (EDHF). The hyperpolarization produced by EDHF always preceded relaxation, and relaxation never occurred at concentrations of acetylcholine that were insufficient to evoke hyperpolarization. 5. The concentration-hyperpolarization and concentration-relaxation curves in response to acetylcholine were not affected by glibenclamide or barium (1-3 mM) but were shifted to the right 4- and 5-fold, respectively, by 1 mM tetraethylammonium. The hyperpolarization and relaxation evoked by acetylcholine were also reduced in a parallel manner when the potassium concentration in the superfusate was increased. 6. Hyperpolarizing current steps, applied to spiral strips of coronary artery denuded of endothelium and depolarized and constricted with U46619, caused relaxation. The relationship between hyperpolarization and relaxation evoked electronically was similar to that which was due to EDHF in intact tissues stimulated with acetylcholine. 7. It is concluded that the ability of NO or Iloprost to relax guinea-pig coronary artery does not depend upon hyperpolarization of the smooth muscle. In contrast, hyperpolarization is likely to play a major, if not the only, role in the relaxation in response to EDHF in this tissue.
 ...
PMID:Role of membrane potential in endothelium-dependent relaxation of guinea-pig coronary arterial smooth muscle. 754 69

1. Streptozotocin-induced diabetic rats (Wistar) were implanted with sustained release insulin pellets (release rate = 4 u day-1) or with placebo pellets (palmitic acid) from the onset of glycosuria. 2. Noradrenaline sensitivity, endothelium-dependent relaxation to acetylcholine and endothelium-independent relaxation to sodium nitroprusside were assessed in mesenteric resistance arteries from the insulin-treated (IT) diabetic animals and compared to placebo-implanted (PI) diabetics and age-matched controls. 3. Arteries from PI-diabetic rats (8-10 weeks) demonstrated an enhanced maximal response to noradrenaline compared to controls, which was not prevented by insulin treatment (control 2.65 +/- 0.17 mN mm-1, n = 18 arteries versus PI-diabetic 3.73 +/- 0.40 mM mm-1, n = 5, P < 0.05; control versus IT-diabetic 4.02 +/- 0.19 mN mm-1, n = 22, P < 0.001). Sensitivity to noradrenaline was similar between the three groups. 4. In the presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), IT and PI arteries were more sensitive to noradrenaline than control arteries (pEC50: control 5.75 +/- 0.08, n = 17, versus PI-diabetic 6.14 +/- 0.09, n = 8, P < 0.05; control versus IT-diabetic 6.38 +/- 0.08, n = 20, P < 0.001). 5. The maximum contractile response to depolarizing 125 mM K+ was significantly enhanced in IT-diabetic arteries but not PI-diabetic when compared to control arteries (maximum response: control 3.74 +/- 0.15 mN mm-1, n = 18, versus PI-diabetic 3.61 +/- 0.19 mN mm-1, n = 11, NS; control versus IT-diabetic 4.66 +/- 0.18 mN mm-1, n = 22, P < 0.001). 6. Endothelium-dependent relaxation to acetylcholine was profoundly impaired in the PI-diabetic arteries, but in the IT-diabetic arteries was not significantly different from controls (pEC50: control 7.64 +/- 0.19, n = 17, versus PI-diabetic 6.07 +/- 0.12, n = 8, P < 0.001; control versus IT-diabetic 7.36 +/- 0.09, n = 22, NS). 7. Endothelium-independent relaxation to sodium nitroprusside was slightly but significantly impaired in the PI-diabetic arteries, but was not significantly different in the IT-diabetic arteries compared to controls (pEC50: control 7.78 +/- 0.10, n = 13, versus PI-diabetic 7.31 +/- 0.13, n = 13, P <0.05; control,versus IT-diabetic 7.64 +/- 0.09, n = 16, NS).
 ...
PMID:Prevention by insulin treatment of endothelial dysfunction but not enhanced noradrenaline-induced contractility in mesenteric resistance arteries from streptozotocin-induced diabetic rats. 801 17

1. The involvement of cyclo-oxygenase (COX) products and nitric oxide (NO) in contractile responses of resistance arteries to angiotensin II (AII) were investigated in small mesenteric arteries from spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. 2. In endothelium intact vessels, AII induced concentration-dependent responses without any significant difference between the two strains. However, removal of functional endothelium resulted in enhanced sensitivity to AII, the pD2 value increasing from 8.4 +/- 0.2 to 8.9 +/- 0.2 (P < 0.05) in WKY and from 8.2 +/- 0.1 to 8.6 +/- 0.1 (P < 0.05) in SHR (not significantly different between strains, n = 9 - 12). In addition, endothelium removal enhanced maximal contractions elicited by AII in SHR (1.4 +/- 0.1 to 2.1 +/- 0.2 mN mm-1, n = 5; P < 0.05) but not in WKY (1.0 +/- 0.1 to 1.2 +/- 0.1 mN mm-1, n = 5) vessels. 3. In the absence of functional endothelium, the COX inhibitor indomethacin (10(-5) M) reduced contractile responses elicited by AII in SHR arteries, resulting in 33 +/- 5% (n = 5) decrease in maximal contraction. However, it produced minimal if any, effect on responses of WKY vessels. In both strains, the TP receptor antagonist GR32191 B (3 x 10(-6) M) did not modify contractions elicited by AII in these conditions. 4. In the presence of functional endothelium, indomethacin (10(-5) M) almost abolished the responses to AII in both strains. GR32191 B (3 x 10(-6) M) reduced the sensitivity of WKY arteries to AII (pD2 = 8.1 +/- 0.1, P < 0.01) without any effect on maximal contraction. In SHR arteries, it markedly reduced maximal contraction (47 +/- 3.5%). 5. In both strains, the NO synthase inhibitor NG-nitro-L-arginine methy lester (L-NAME; 10(-4) M) had no effect in the absence of functional endothelium but it markedly reduced the inhibitory influence of endothelium on contractile responses to AII. Furthermore, in arteries with endothelium, it reduced the effect of both indomethacin and GR32191 B to the same level as observed in vessels without functional endothelium. 6. The results suggest that enhanced contraction caused by COX products was counteracted by enhanced relaxation caused by endothelium-derived NO in resistance mesenteric arteries of the SHR exposed to AII, compared to WKY arteries. The COX products involved in alterations of SHR responses comprised an endothelium-derived prostaglandin activating TP receptors and another nonendothelial unidentified vasoconstrictor compound which did not activate these receptors.
 ...
PMID:Alterations of cyclo-oxygenase products and NO in responses to angiotensin II of resistance arteries from the spontaneously hypertensive rat. 898 12

1. We investigated the response to pressure (myogenic tone) and flow of rat mesenteric resistance arteries cannulated in an arteriograph which allowed the measurement of intraluminal diameter for controlled pressures and flows. Rats were treated for 3 weeks with NG-nitro-L-arginine methyl ester (L-NAME, 50 mg kg-1 day-1) or L-NAME plus the angiotensin I converting enzyme inhibitor (ACEI) quinapril (10 mg kg-1 day-1). 2. Mean blood pressure increased significantly in chronic L-NAME-treated rats (155 +/- 4 mmHg, n = 8, vs control 121 +/- 6 mmHg, n = 10; P < 0.05). L-NAME-treated rats excreted significantly more dinor-6-keto prostaglandin F1 alpha (dinor-6-keto PGF1 alpha), the stable urinary metabolite of prostacyclin, than control rats. The ACEI prevented the rise in blood pressure and the rise in urinary dinor-6-keto PGF1 alpha due to L-NAME. 3. Isolated mesenteric resistance arteries, developed myogenic tone in response to stepwise increases in pressure (42 +/- 6 to 847 +/- 10 mN mm-1, from 25 to 150 mmHg, n = 9). Myogenic tone was not significantly affected by the chronic treatment with L-NAME or L-NAME + ACEI. 4. Flow (100 microliters min-1) significantly attenuated myogenic tone by 50 +/- 6% at 150 mmHg (n = 10). Flow-induced dilatation was significantly attenuated by chronic L-NAME to 22 +/- 6% at 150 mmHg (n = 10, p = 0.0001) and was not affected in the L-NAME + ACEI group. 5. Acute in vitro NG-nitro-L-arginine (L-NOARG, 10 microM) significantly decreased flow-induced dilation in control but not in L-NAME or L-NAME + ACEI rats. Both acute indomethacin (10 microM) and acute NS 398 (cyclo-oxygenase-2 (COX-2) inhibitor, 1 microM) did not change significantly flow-induced dilatation in controls but they both decreased flow-induced dilatation in the L-NAME and L-NAME + ACEI groups. Acute Hoe 140 (bradykinin receptor inhibitor, 1 microM) induced a significant contraction of the isolated mesenteric arteries which was the same in the 3 groups. 6. Immunofluorescence analysis of COX-2 showed that the enzyme was expressed in resistance mesenteric arteries in L-NAME and L-NAME + ACEI groups but not in control. COX-1 expression was identical in all 3 groups. 7. We conclude that chronic inhibition of nitric oxide synthesis is associated with a decreased flow-induced dilatation in resistance mesenteric arteries which was compensated by an overproduction of vasodilator prostaglandins resulting in part from COX-2 expression. The decrease in flow-induced dilatation was prevented by the ACEI, quinapril.
 ...
PMID:Alteration of flow-induced dilatation in mesenteric resistance arteries of L-NAME treated rats and its partial association with induction of cyclo-oxygenase-2. 914 91

1. The pulmonary vasculature is normally in a low resting state of tone. It has been hypothesized that this basal tone is actively maintained by the continuous release of a vasodilator in the resting state. However, evidence for basal release of nitric oxide (NO) is inconclusive. 2. We studied the release of NO in arteries from the pulmonary circulation of male Wistar-Kyoto rats by examining the effects of the L-arginine analogue NG-nitro-L-arginine methyl ester (L-NAME) on resting pulmonary arteries and on vessels pre-contracted with prostaglandin F2(alpha) (PGF2 alpha). 3. Rats (n = 21) were killed by an overdose with pentobarbitone. Pulmonary arteries were dissected (mean internal diameter 459 +/- 11 microns) and mounted in a small vessel wire myograph. Resting tensions were to set to stimulate transmural pressures of 17.5 mmHg. 4. L-NAME (100 microM) was found to produce a contraction of 0.64 +/- 0.09 mN mm-1 in resting pulmonary arteries when added alone to the myograph bath. This contraction was not produced following removal of the endothelium. Vessel contraction to PGF(2 alpha) (100 microM) was found to be significantly greater when carried out in the presence of L-NAME (100 microM) -1.37 +/- 0.15 mN mm-1 compared with 1.96 +/- 0.17 mN mm-1. Dilation following acetylcholine (ACh) (1 microM) was abolished in the presence of L-NAME (100 microM). 5. Rat pulmonary artery contraction in response to the addition of L-NAME and the absence of contraction upon removal of the endothelium provides supportive evidence of the active release of nitric oxide for the maintenance of resting tone.
 ...
PMID:Response of normoxic pulmonary arteries of the rat in the resting and contracted state to NO synthase blockade. 929 34

Nitric oxide (NO) inhibits transport in various nephron segments, and the thick ascending limb of the loop of Henle (TALH) expresses NO synthase (NOS). However, the effects of NO on TALH transport have not been extensively studied. We hypothesized that endogenously produced NO directly decreases NaCl transport by the TALH. We first determined the effect of exogenously added NO on net chloride flux (JCl). The NO donor spermine NONOate (SPM; 10 microM) decreased JCl from 101.2 +/- 9.6 to 65.0 +/- 7.7 pmol. mm-1. min-1, a reduction of 35.5 +/- 6.4%, whereas controls did not decrease over time. To determine whether endogenous NO affects cortical TALH transport, we measured the effect of adding the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the substrate L-arginine (L-Arg), or its enantiomer D-arginine (D-Arg) on JCl. L-NAME and D-Arg did not alter JCl; in contrast, addition of 0.5 mM L-Arg decreased JCl by 40.2 +/- 10.4% from control. The inhibition of chloride flux by 0.5 mM L-Arg was abolished by pretreatment with L-NAME, indicating that cortical TALH NOS is active, but production of NO is substrate-limited in our preparation. Furthermore, cortical TALH chloride flux increased following removal of 0.5 mM L-Arg from the bath, indicating that the reductions in chloride flux observed in response to L-Arg are not the result of NO-mediated cytotoxicity. We conclude that 1) exogenous NO decreases cortical TALH JCl; 2) cortical TALHs produce NO in the presence of L-Arg, which decreases JCl; and 3) the response of cortical TALHs to L-Arg is reversible in vitro. These data suggest an important role for locally produced NO, which may act via an autocrine mechanism to directly affect TALH sodium chloride transport. Thus TALH NO synthesis and inhibition of chloride transport may contribute to the diuretic and natriuretic effects of NO observed in vivo.
 ...
PMID:Endogenous nitric oxide inhibits chloride transport in the thick ascending limb. 988 91