UMLS:C0406810 - FACTA Search

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

Previous results have shown that the contractile response to norepinephrine (NE) was enhanced in isolated aortae from SHR and normotensive Wistar parathyroidectomized rats. In this work we sought to characterize the contribution of endothelium-derived relaxing factor (EDRF) release to this effect which is not linked to hypertension. Parathyroidectomy (PTX) was performed by surgery on 5 week-old male Wistar rats. Five weeks later intact (E+) and rubbed (E-) aortic rings were mounted in an organ chamber for isometric tension recording. KCl-induced contractions were potentiated in PTX E+ aortae compared to sham operated (SO), (P < 0.05), but not in denuded E- aortae. Similarly NE (1 nM- 10 microM) induced a potentiated contractile response in PTX E+ (P < 0.01), but not in PTX E- rings; nevertheless the sensitivity did not change. After removal of endothelium, the expected enhanced contraction and sensitivity observed in SO rats was not present in PTX. The NO synthase inhibitor L-NAME (20 microM), enhanced sensitivity to NE in SO but not in PTX E+ aortic rings. In addition, hemoglobin (Hb, 10 microM) enhanced NE contraction in SO (P < 0.01) aortic rings, but to a lesser extent in PTX rat aortae. Moreover, in the presence of L-NAME or Hb, SO and PTX aortae displayed a similar contraction. Superoxide dismutase (SOD, 150 U/ml) diminished the NE contraction since NO was protected from degradation but the difference was still present between SO and PTX rat aortae, ruling out the possible implication of superoxide anions in the hyperreactivity of PTX aortae. On the other hand, A23187, which induces EDRF release, reduced the level of NE contraction as expected, but suppressed the PTX enhancing effect and in calcium-free solution the enhancement of contraction after PTX was not observed. These experiments extend to the rat the observations previously obtained in rabbit aorta: extracellular calcium is a major determining factor in NO production. Acetylcholine and A23187 (cumulative doses) produced an endothelium-dependent relaxation which was not significantly modified in NE-pre-contracted PTX aortae compared to SO aortae. L-arginine (100 microM), reversed the L-NAME inhibitory effect and induced an attenuated endothelium-dependent relaxation in PTX vessels (P < 0.01). In conclusion, in rat isolated aortae the enhancing effect of parathyroidectomy on norepinephrine and KCl contractions is due to a diminished endothelial nitric oxide production. This might arise via a decrease of the constitutive NO synthase activity in an extracellular calcium-dependent manner.
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PMID:Characterization of endothelium-derived relaxing factor involvement in the potentiating effect of parathyroidectomy on norepinephrine-induced rat aortic contraction. 818 95

1. The role of nitric oxide in the cerebral circulation under basal conditions and after vasodilator stimulation was studied in instrumented, conscious goats, by examining the action of inhibiting endogenous nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME). 2. In 6 unanaesthetized goats, blood flow to one brain hemisphere (electromagnetically measured), systemic arterial blood pressure and heart rate were continuously recorded. L-NAME (35 mg kg-1 by i.v. bolus) decreased resting cerebral blood flow by 43 +/- 3%, increased mean arterial pressure by 21 +/- 2%, and decreased heart rate by 41 +/- 2%; cerebrovascular resistance increased by 114 +/- 13% (P < 0.01); the immediate addition of i.v. infusion of L-NAME (0.15-0.20 mg kg-1 during 60-80 min) did not significantly modify these effects. Cerebral blood flow recovered at 72 h, arterial pressure and cerebrovascular resistance at 48 h, and heart rate at 6 days after L-NAME treatment. 3. A second treatment with L-NAME scheduled as above reproduced the immediate haemodynamic effects of the first treatment, which (except bradycardia) reversed with L-arginine (200-300 mg kg-1 by i.v. bolus). 4. Acetylcholine (0.01-0.3 micrograms), sodium nitroprusside (3-100 micrograms) and diazoxide (0.3-9 mg), injected into the cerebral circulation of 5 conscious goats, produced dose-dependent increases in cerebral blood flow, and decreases in cerebrovascular resistance; sodium nitroprusside (30 and 100 micrograms) also caused hypotension and tachycardia. 5. The reduction in cerebrovascular resistance from resting levels (in absolute values) to lower doses,but not to the highest dose, of acetylcholine was diminished, to sodium nitroprusside was increased, and to diazoxide was unaffected after L-NAME, compared to control conditions. The effects on cerebrovascular resistance to acetycholine normalized within 24 h and to sodium nitroprusside within 48 h after L-NAME treatment.6. This study provides information about the evolution of the changes in cerebral blood flow and cerebrovascular reactivity after inhibition of endogenous nitric oxide in conscious animals. The results suggest: (a) endogenous nitric oxide is involved in regulation of the cerebral circulation by producing a resting vasodilator tone, (b) the cerebral vasodilatation to acetylcholine is mediated, at least in part, by nitric oxide release, and (c) inhibition of nitric oxide production induces supersensitivity of cerebral vasculature to nitrovasodilators.
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PMID:Cerebral blood flow and cerebrovascular reactivity after inhibition of nitric oxide synthesis in conscious goats. 822 Sep 4

We investigated the effects of inhibition of both nitric oxide (NO) synthesis and angiotensin converting enzyme (ACE) on agonist-induced relaxations in the coronary system. Chronically instrumented conscious dogs (n = 4) were prepared for the measurement of coronary blood flow (CBF), coronary diameter of the left circumflex artery (LCX), mean arterial blood pressure (MAP) and heart rate (HR). Intracoronary infusions of acetylcholine, adenosine and bradykinin were performed after intracoronary pretreatment of either vehicle, L-NAME (6 mg.kg-1), captopril (1 mg.kg-1) or both L-NAME+captopril. Acetylcholine bradykinin and adenosine caused dose-dependent increases in CBF and LCX. HR increased concomitantly. Captopril potentiated the vasodilating effects of bradykinin and acetylcholine on LCX and CBF significantly (P < or = 0.05) and those of adenosine slightly. L-NAME caused vasoconstriction, hypertension and bradycardia. The effects of acetylcholine on CBF were abolished during L-NAME treatment while bradykinin and adenosine responses were markedly reduced. When captopril and L-NAME were given simultaneously, the vasodilator responses to bradykinin but not to acetylcholine or adenosine were partially restored (P < or = 0.05). We conclude that in vivo, (a) adenosine possibly elicits endothelium-dependent dilation; (b) adenosine and bradykinin act in part independently of the L-arginine/NO pathway; (c) vasodilation to acetylcholine is potentiated by acute ACE inhibition via NO-dependent mechanisms.
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PMID:Coronary vasodilation to acetylcholine, adenosine and bradykinin in dogs: effects of inhibition of NO-synthesis and captopril. 829 69

The cavernous carotid artery, that portion of the internal carotid artery that lies within the intracranial cavernous sinus, is covered by arterial (luminal surface) and venous (external surface) endothelium. The reactivity of the isolated canine, cavernous carotid artery, precontracted with 10(-5) M 5-hydroxytryptamine, was studied by using in vitro perfusion and superfusion to evaluate the effects of vasoactive stimuli applied to the internal or external surface. Acetylcholine (10(-8)-10(-4) M), thrombin (0.01-1 U/ml) or calcium ionophore A23187 (10(-8) - 10(-6) M) on the luminal side produced concentration-dependent relaxations which were reduced by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) or by removing either the internal or both endothelia. Thrombin or ionophore A23187 on the external side produced concentration-dependent contractions which were reduced by removing either the external or both endothelia, and by meclofenamate (10(-5) M). Acetylcholine on the external side, produced a concentration-dependent contraction that was unaffected by meclofenamate or by removing the external or both endothelia. Sodium nitroprusside (10(-7) - 10(-5) M) induced similar relaxation on both sides and regardless of whether the arteries were with or without endothelium. These results suggest firstly, that the cavernous carotid artery responds to acetylcholine, thrombin or calcium ionophore A23187 by relaxing or contracting when these agents act on the luminal or the external surface respectively. Secondly, the arterial endothelium mediates relaxation to these three substances by releasing NO, whereas the venous endothelium mediates contraction to thrombin and ionophore A23187 by releasing a cyclooxygenase product.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reactivity of the dog cavernous carotid artery. The role of the arterial and venous endothelium. 830 86

The influence of diabetes on the function of vascular endothelium was examined with respect to the role of nitric oxide (NO) in the regulation of blood pressure (BP) in vivo, the vascular relaxation, and levels of cAMP and cGMP in the effluent of the perfused mesenteric arterial bed from streptozotocin-induced diabetic rats. An intravenous injection of 100 mg/kg N omega-nitro-L-arginine methylester (L-NAME) caused hypertension in both diabetic rats and controls. However, the degree of hypertension in the diabetic rats was significantly lower than that in the controls. Acetylcholine (ACh)-induced vasorelaxation of the perfused mesenteric arterial bed decreased in diabetic rats. At the same time, the levels of cAMP and cGMP in the effluent of the diabetic rats were also lower than in the controls. These data indicate that NO formation is involved in the regulation of BP in rats, and is decreased in diabetic rats, due to an impairment of the vascular endothelium, including the endothelium of resistance vessels.
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PMID:Changes in endothelium-dependent relaxation and levels of cyclic nucleotides in the perfused mesenteric arterial bed from streptozotocin-induced diabetic rats. 839 May 94

Endothelium-dependent relaxation is associated with smooth muscle hyperpolarization in many arteries which may account for relaxation that persists in the presence of nitric oxide inhibitors such as NG-nitro-L-arginine methyl ester (L-NAME). Acetylcholine (ACh)-induced relaxations of the rabbit thoracic and abdominal aorta and iliac and carotid arteries were studied for the relative contribution of nitric oxide-dependent and -independent mechanisms in rings suspended for measurement of isometric tension. Although relaxation of the thoracic aorta to ACh (10(-6) M) was almost blocked completely by L-NAME (3 x 10(-5) M), the maximal relaxation in the abdominal aorta, carotid and iliac arteries was only reduced by 28, 26 and 62%, respectively. In rings of abdominal aorta, L-NAME blocked the ACh-stimulated (10(-6) M) rise in cyclic GMP verifying that relaxation which persists in L-NAME-treated rings is not mediated by nitric oxide. The L-NAME resistant response was nearly abolished by elevated external K+ in rings of abdominal aorta and carotid artery, suggesting this relaxation may be mediated by a membrane potential sensitive mechanism. Furthermore, tetraethylammonium (10(-3) M) partially and charybdotoxin (5 x 10(-8) M) completely inhibited the remaining L-NAME-resistant relaxation in both abdominal aorta and carotid artery, suggesting a role for Ca(++)-activated K(+)-channels. Blockers of ATP-sensitive K+ channels also inhibited the L-NAME resistant relaxation in the abdominal aorta only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potassium channel-mediated relaxation to acetylcholine in rabbit arteries. 839 36

Endothelium-dependent relaxation of mesenteric resistance arteries of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats was studied. Acetylcholine-induced relaxation of SHR vessels precontracted with 10 microM norepinephrine was endothelium dependent and attenuated compared with WKY vessels. The impaired response of SHR vessels was normalized by inhibition of cyclooxygenase with indomethacin. Blockade of nitric oxide synthetase with NG-nitro L-arginine methyl ester (L-NAME) or inhibition of guanylate cyclase with methylene blue attenuated acetylcholine-induced relaxation of norepinephrine-contracted SHR vessels but had no effect on WKY vessels. When vessels were precontracted with 30 nM arginine vasopressin, acetylcholine induced similar degrees of relaxation in both strains. A similar response was detected when lysine vasopressin was used to induce tone. Indomethacin had no effect on relaxation responses of SHR and WKY vessels precontracted with either form of vasopressin. L-NAME and methylene blue partially inhibited acetylcholine-induced relaxation of vasopressin-contracted vessels from both strains. Acetylcholine added at baseline did not induce contraction of vessels from either strain. It is concluded that endothelium-dependent relaxation of SHR resistance arteries is not impaired under all circumstances. Acetylcholine-induced relaxation may be suppressed in SHR resistance arteries when norepinephrine is used to induce contraction as a result of catecholamine-induced production of an endothelium-derived contracting factor. Vasopressin, on the other hand, does not elicit production of this contracting factor and may enhance the vasorelaxant action of acetylcholine in resistance arteries of both strains via actions on endothelial or vascular smooth muscle cells.
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PMID:Endothelium-dependent relaxation of hypertensive resistance arteries is not impaired under all conditions. 841 84

Biochemical signaling determines the specific action of vasomediators in the control of microvascular permeability and tone. We tested the hypothesis that nitric oxide (NO) synthesis is involved in the biochemical signaling pathway of platelet activating factor (PAF). The cheek pouch of anesthetized male Syrian hamsters was used as a microvascular model. Vessel diameter [expressed as the ratio of the experimental to the control (e/c) diameter, with control diameter normalized to 1] and extravasation of FITC-dextran 150 by integrated optical intensity (IOI) were determined using intravital fluorescent microscopy and computer-assisted digital image analysis. N-Nitro-L-arginine methyl ester (L-NAME) at 10(-5) and 10(-6) M and N-nitro-L-mono-methyl arginine (L-NMMA) at 10(-4) and 10(-5) M were used as inhibitors of NO synthase (NOS). Acetylcholine (ACh) and bradykinin were used as indirect indices of NOS activation. L-NAME and L-NMMA attenuated both ACh and bradykinin vasodilatory effects as well as the bradykinin-induced increase in vascular permeability. Topical PAF (10(-7) M) caused vasoconstriction (mean +/- SEM e/c ratio = 0.3 +/- 0.1) and increased IOI from a normalized baseline of 0 to 67.4 +/- 12.8. Topical administration of L-NAME produced differential effects on the series-arranged arterioles but had no effect on postcapillary venular permeability. L-NMMA did not influence the basal arteriolar diameter, but at 10(-5) M it caused a small increase in permeability (IOI = 14.3 +/- 4.2). In the presence of NOS inhibitors, PAF caused a reduced arteriolar constriction (e/c ratio = 0.6 +/- 0.1) relative to PAF alone. Both NOS inhibitors reduced the PAF-stimulated increase in vasopermeability. At 10(-5) M L-NMMA, the PAF-stimulated IOI mean value was 26.1 +/- 5.2, while at 10(-4) M L-NMMA the PAF-stimulated IOI was 15.2 +/- 2.6 compared to 10(-7) M PAF (67.4 +/- 12.8). These results support our hypothesis that NO synthesis is a step in the biochemical signaling pathway of the postcapillary cellular responses to PAF.
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PMID:Platelet activating factor modulates microvascular permeability through nitric oxide synthesis. 853 2

The main objective of this work was to study the role of potassium channels in the cholinergic relaxation of cutaneous arteries during cooling. Acetylcholine (10(-8)-10(-4) M) produced isometric concentration-dependent relaxation of precontracted segments of rabbit ear (cutaneous) and femoral (noncutaneous) arteries; this relaxation was higher at 24 degrees C (cooling) than at 37 degrees C in ear, but not in femoral, arteries. In both types of arteries, at 37 and 24 degrees C, the relaxation to acetylcholine was partially reduced by the inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), and the relaxation that remained after L-NAME was higher at 24 degrees C than at 37 degrees C in ear, but not in femoral, arteries. At 37 and 24 degrees C, the persistent relaxation to acetylcholine after L-NAME was further reduced by smooth muscle depolarization with medium containing a high concentration of potassium (6 x 10(-2) M), and with the nonspecific inhibitors of potassium channels tetraethylammonium (10(-2) M) or 4-aminopyridine (5 x 10(-3) M) in both ear and femoral arteries. In ear arteries, the inhibitor of high conductance calcium-activated potassium channels charybdotoxin (10(-7) M), alone or combined with L-NAME, reduced the relaxation to acetylcholine at 24 degrees C, but not at 37 degrees C. In femoral arteries, charybdotoxin alone did not modify, but combined with L-NAME reduced, the relaxation to acetylcholine at either temperature. At 37 and 24 degrees C, the inhibitor of low conductance calcium-activated potassium channels apamin (10(-7) M), the inhibitor of ATP-dependent potassium channels glibenclamide (10(-5) M) and the cyclooxygenase inhibitor meclofenamate (10(-5) M), alone or combined with L-NAME, did not modify the relaxation of both ear and femoral arteries to acetylcholine. These results suggest: (1) the cholinergic relaxation of cutaneous (ear) and noncutaneous (femoral) arteries could be mediated by endothelial nitric oxide and by activation of potassium channels, and (2) cooling increases the relaxation of cutaneous arteries to cholinergic stimulation, which may be mediated, in part, by an increased response of potassium channels.
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PMID:Role of nitric oxide and potassium channels in the cholinergic relaxation of rabbit ear and femoral arteries: effects of cooling. 856 11

The signal transduction cascade between the activation of the somatostatin (SOM) receptor and modulation of transmitter release was study using Acetylcholine (Ach) release measurements and patch clamp recordings of Ca2+ current from acutely dissociated St 40 ciliary ganglion neurons. As in intact synapses, somal ACh release was blocked by 100 nM SOM or 100 microM dibutyril cGMP, and the SOM-mediated inhibition could be reversed by 10 microM 1-NAME (a selective inhibitor of nitric oxide synthase, NOS) or 100 microM Rp-8p-CPT-cGMPs (a selective inhibitor of a cGMP protein dependent kinase, PKG). In whole cell recordings, SOM inhibition of Ca2+ current rapidly relaxes to control levels but is sustained in perforated patch recordings which decreases cell dialysis. Inhibition of NOS or PKG in perforated patch recordings, however caused SOM effects to become transient again. We hypothesize that PKG alters the characteristics of the membrane-delimited G protein inhibition of Ca2+ current. Therefore SOM receptors trigger a membrane-delimited signal transduction cascade that is modulated by soluble messengers, converging on voltage activated Ca2+ channels. When both pathways are active together, SOM causes a sustained inhibition of neuronal Ca2+ current leading to a decrease in transmitter release.
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PMID:Membrane delimited and intracellular soluble pathways in the somatostatin modulation of ACh release. 863 27

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