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)

To determine whether inhibition of endothelium-derived nitric oxide (EDNO) synthesis enhances the effects of exogenous vasoconstrictor agents on the coronary vasculature, we examined the effects of neuropeptide Y (NPY), clonidine, and ergonovine on coronary vascular resistance (CVR) with and without EDNO inhibitor and compared the results. In 15 anesthetized mongrel dogs, the left circumflex coronary artery (LCX) was perfused with arterial blood from the left common carotid artery through an extracorporeal bypass tube and LCX blood flow was measured with an electromagnetic flowmeter. Nine of the dogs were pretreated with intracoronary NG-nitro-L-arginine methyl ester (L-NAME 300 microM in LCX blood) (L-NAME group) and the other 6 were treated with normal saline (vehicle group). Three doses of NPY (4.3, 43, 430 ng/kg), two doses of clonidine (30 and 300 ng/kg), and one dose of ergonovine (20 micrograms/kg) were infused into LCX. NPY decreased LCX flow and increased CVR dose dependently in both groups, and there was no significant difference in the dose-response relation between the two groups. Clonidine decreased LCX flow and increased CVR in both groups, and there was no difference in the effect between the groups. In contrast, ergonovine decreased LCX flow and increased CVR to a greater degree in the L-NAME group than in the vehicle group (p < 0.01). Thus, inhibition of EDNO synthesis by L-NAME did not result in enhancement of the vasoconstrictor effects of NPY and clonidine, whereas it significantly enhanced the effect of ergonovine, possibly through inhibition of ergonovine-induced EDNO release.
 ...
PMID:Influence of inhibition of endothelium-derived nitric oxide formation to effects of vasoconstrictor agents neuropeptide Y, clonidine, and ergonovine on coronary vascular resistance. 752 96

Previously, we demonstrated that two nonselective inhibitors of nitric oxide synthase (NOS), L-NG-nitroarginine (L-NNA) and L-NG-nitroarginine methyl ester (L-NAME), reduced some signs of morphine withdrawal in rats. The present work extended these studies to include 7-nitroindazole (7-NI), an inhibitor specific for cerebral NOS, and N(5)-(1-iminoethyl)-L-ornithine (L-NIO), a potent inhibitor of endothelial NOS. Behavioral effects of these four NOS inhibitors and clonidine, an alpha 2-adrenoceptor, agonist, on morphine withdrawal in rats were assessed. Rats received one 75-mg morphine pellet subcutaneously (SC). Three days later, NOS inhibitors were administered IP 1 h before withdrawal was precipitated with naloxone (0.5 mg/kg, SC) and scored. 7-NI, L-NIO, L-NAME and L-NNA produced dose-related decreases in weight loss, diarrhea, wet dog shakes and grooming. 7-NI also reduced mastication, salivation and genital effects. Clonidine produced effects similar to 7-NI. In awake, morphine-naive and morphine-dependent rats not subjected to withdrawal, 7-NI was the only NOS inhibitor that did not increase blood pressure. Because 7-NI attenuated more signs of opioid withdrawal than L-NNA, L-NAME or L-NIO without causing hypertension, 7-NI appears to warrant further testing as a potential candidate for human use.
 ...
PMID:Comparison of 7-nitroindazole with other nitric oxide synthase inhibitors as attenuators of opioid withdrawal. 756 21

The aim of this study was to elucidate whether nitric oxide (NO) is involved in re-innervation of rat molar tooth pulp following transection of the inferior alveolar nerve. The inferior alveolar nerves (IAN) of rats were transected unilaterally under anesthesia with chloral hydrate. The animals received horseradish peroxidase (HRP) application to mandibular molar tooth pulps on both sides and were fixed by transvascular perfusion. The average number of labeled cells on each side of the trigeminal ganglion was not significantly different [101 +/- 11 (mean +/- S.E.M.; n = 6, left) and 89 +/- 11 (n = 6, right)]. With HRP application on postoperative day 3, the ratio of the number of labeled neurons in the transected vs. non-transected (contralateral) sides was 31.5 +/- 5.8% (n = 11). The i.p. administration of N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg, once a day for a period of 4 days), but not D-NAME, significantly decreased the ratio of the number of labeled neurons (10.1 +/- 7.0%, n = 10). L-Arginine (300 mg/kg, i.p., once a day for a period of 4 days) slightly increased the number of labeled neurons on the transected side. Clonidine (25 microg/kg, i.p., once a day for a period of 4 days) failed to exhibit any significant effect on nerve regeneration. In the trigeminal ganglion ipsilateral to the transected IAN on postoperative day 4, NADPH-diaphorase (NADPH-d)-positive neurons had significantly increased. On the other hand, no changes in NADPH-d were observed in the superficial layers of the subnucleus caudalis of the spinal trigeminal nucleus from where primary neurons innervating the mammalian tooth pulp project. These results suggest that NO is involved in several mechanisms related to neuronal regeneration.
 ...
PMID:Involvement of nitric oxide in re-innvervation of rat molar tooth pulp following transection of the inferior alveolar nerve. 920 Apr 96

We are investigating the influence of NO synthetase inhibitor on the clonidine-induced cardiovascular actions in urethane-anesthetized rats. The systemic blood pressure was measured from right femoral artery, heart rate from the pressure pulse under inhalation of O2. Nw-nitro-L-arginine-methylester (L-NAME, 5 mg/kg), NO synthetase inhibitor, administered intravenously increased blood pressure slightly, although decreased heart rate. The responses to L-NAME were stable about 10 min after the injection. Clonidine (5 mg/kg) administered intravenously indicated the transient increase blood pressure and following continuous decrease of blood pressure. The early transient hypertension of clonidine was potentiated by pretreatment with L-NAME and later continuous hypotension was markedly inhibited. While, the early transient hypertension of clonidine was inhibited by pretreatment with L-arginine and later continuous hypotension was potentiated. The hypertension and tachycardia of intravenous tyramine was enhanced by L-NAME. Clonidine administered into the cerebroventricle did not indicate the early transient hypertension, though produced the later continuous hypotension. These results suggest that L-NAME modifies the cardiovascular responses to clonidine and NO may participate in the modulation.
 ...
PMID:[Influence of nitric oxide synthetase inhibitor on the blood pressure action of clonidine in rats]. 1019 Jan 48

The antihypertensive mechanism of alpha2-adrenoceptor agonists, such as clonidine and rilmenidine, is not completely elucidated, although it is probably due to reduction of sympathetic tone mediated by stimulation of central alpha2-adrenoceptors. Because activation of alpha2-adrenoceptors on endothelial cells induces release of endothelium-derived relaxing factor (EDRF), we determined whether nitric oxide (NO) release is involved in the antihypertensive action of clonidine and rilmenidine. In chloralose-anesthetised Wistar rats, systolic and diastolic arterial blood pressures were recorded on a polygraph. Intravenous injection of clonidine or rilmenidine (control group) caused a rapid increase of arterial blood pressure. followed by a long-lasting hypotensive effect. The hypotensive effects, estimated as the area enclosed by the decrease in diastolic pressure during the 20 min after clonidine and rilmenidine injections, were 574+/-60 and 410+/-59 mm Hg/min, respectively. The delta decrease in diastolic arterial blood pressure observed 20 min after intravenous injections of clonidine and rilmenidine was 48+/-5 and 34+/-3 mm Hg, respectively. Clonidine and rilmenidine injected 5-10 min after intravenous pretreatment with L-NAME (2 and 1 mg/kg) or methylene blue (10 mg/kg) induced hypotensive effects that were significantly smaller than that observed for the control group. These results suggest that the antihypertensive effects of clonidine and rilmenidine also may be modulated by the NO-cyclic guanosine monophosphate (cGMP) pathway at the level of the central nervous system and/or at the vascular peripheral circulation.
 ...
PMID:Actions of L-NAME and methylene blue on the hypotensive effects of clonidine and rilmenidine in the anesthetized rat. 1081 83

Xylazine is an adrenergic alpha(2) agonist, which is used in veterinary medicine as a sedative and anesthetic agent. In this work we found that xylazine administered in vivo at a dose of 2.5 mg/kg enhanced spleen cell proliferation and interleukin 2 (IL-2) production in cultures stimulated with concanavalin A (Con A), whereas doses of 10 and 25 mg/kg were inhibitory. A similar stimulatory (10 microM) and inhibitory (50-500 microM) effect on splenocyte proliferation and IL-2 production was observed in vitro. Clonidine, another alpha(2) adrenergic agonist, only had a stimulatory proliferative effect on splenocytes. Yohimbine, an alpha(2) adrenergic antagonist, abrogated the stimulatory action of both clonidine and xylazine, but not the suppressive proliferative activity of xylazine in vitro. The inhibited proliferation of splenocytes to Con A correlated with increased apoptosis of T cells. The apoptosis was not blocked by yohimbine or antibodies to Fas and Fas-L. N-Nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, enhanced proliferation of splenocytes to Con A, partly abrogated the inhibitory effect of xylazine in the proliferation assay, and, only at high concentration (1000 microM), partly suppressed apoptosis of lymphocytes. The enhancing effect of L-NAME on the Con A-induced proliferation of splenocytes correlated with decreased NO production. However, decreased NO production observed in cultures with xylazine was followed by both decreased lymphocyte proliferation and apoptosis. Cumulatively, these results suggest that the immunosuppressive properties of xylazine on splenocytes in vitro are due to increased apoptosis of lymphocytes, predominantly involve NO-independent pathways, and are probably independent of its action through alpha(2) adrenoreceptors.
 ...
PMID:Immunomodulatory effect of xylazine, an alpha(2) adrenergic agonist, on rat spleen cells in culture. 1113 73

Functional role of endothelial alpha(2)-adrenoceptor in coronary circulation remains unclear. Clonidine, an agonist of alpha(2)-adrenoceptors, was reported to induce coronary vasodilatation via stimulation of endothelial alpha(2)-adrenoceptors or coronary vasoconstriction involving vascular smooth muscle alpha(2)-adrenoceptors. Moreover, H(2) receptor-dependent responses to clonidine were described. Here, we reassess the contribution of endothelial alpha(2)-adrenoceptor and H(2) receptors to coronary flow and contractility responses induced by clonidine in the isolated guinea pig heart. We found that clonidine (10(-9) - 10(-6) M) produced concentration-dependent coronary vasoconstriction without a significant change in contractility. This response was inhibited by the alpha(1)/alpha(2)-adrenoceptor antagonist - phentolamine (10(-5) M) and the selective alpha(2)-adrenoceptor antagonist yohimbine (10(-6) M), but it was not changed by the selective alpha(1)-adrenoceptor antagonist prazosin (10(-6) M). In the presence of nitric oxide synthase inhibitor, L-NAME (10(-4) M) the clonidine-induced vasoconstriction was potentiated. Clonidine at high concentrations of 10(-5) - 3 x 10(-5) M produced coronary vasodilatation, and an increase in myocardial contractility. These responses were abolished by a selective H(2)-receptor antagonist, ranitidine (10(-5) M), but not by phentolamine (10(-5) M). We conclude that in the isolated guinea pig heart, clonidine-induced vasoconstriction is mediated by activation of smooth muscle alpha(2)-adrenoceptors whereas clonidine-induced coronary vasodilatation is mediated by activation of vascular H(2) histaminergic receptors. Accordingly, endothelial alpha(2)-adrenoceptors does not seem to play a major role in coronary flow response induced by clonidine.
 ...
PMID:Clonidine-induced coronary vasodilatation in isolated guinea pig heart is not mediated by endothelial alpha2 adrenoceptors. 1472 7

To determine if and how clonidine and tricyclic antidepressants affect gastric contractility. Guinea pig fundic and antral circular muscle strips were studied in vitro. The effects of clonidine or amitriptyline added in graded concentrations on contractions to electric field stimulation (EFS), acetylcholine (ACh), and SP in the presence of N(epsilon)-nitro-l-arginine methyl ester (l-NAME) were studied. EFS produced frequency dependent contractions of fundic and antral muscle that were abolished by atropine or tetrodotoxin (TTX). ACh contractions were abolished by atropine but not TTX. Clonidine reduced contractile response to EFS but had no effect on ACh contractions. The threshold concentration of clonidine to inhibit EFS contractions was lower in the fundus than in the antrum. Amitriptyline reduced contractions to both EFS and ACh but not to SP. The threshold concentration of amitriptyline to inhibit EFS contractions was lower in the antrum than in the fundus. Both clonidine and amitriptyline affect gastric contractility. At threshold concentrations, clonidine affects fundic contractility whereas amitriptyline affects antral contractility. Clonidine affects gastric contractility in response to EFS but not to ACh, suggesting alpha-2 receptors on cholinergic nerves that reduce ACh release. Amitriptyline inhibits gastric contractility to EFS and ACh suggesting an inhibitory muscle effect.
 ...
PMID:Effects of clonidine and tricyclic antidepressants on gastric smooth muscle contractility. 1508 68

Cholestasis is associated with vascular changes and in previous studies decreased response of visceral vessels of cholestatic animals to phenylephrine and acetylcholine has been shown. In the present study, the response of mesenteric vascular bed of cholestatic rats to clonidine (an alpha2-adrenoceptor agonist) was investigated and we also examined the role of endogenous opioids and nitric oxide (NO). Seven-day ligation of bile duct was used as the model to study cholestasis. Six groups of rats, each of which divided into two subgroups (bile duct-ligated and sham-operated), were examined. Three groups of animals were chronically treated with either normal saline, naltrexone (an opioid receptor antagonist, 20 mg/kg/day, s.c.) or aminoguanidine (a selective inducible nitric oxide synthase inhibitor, 150 mg/kg/day, s.c.) for 7 days. After 7 days the response of the mesenteric vascular bed to subsequent doses of clonidine was studied. In other two groups, 7 days after the operation, the response of the mesenteric vascular bed to clonidine in the presence of either yuhimbine, an alpha2-adrenoceptor antagonist, or N(omega)-nitro-L-arginine methyl ester (L-NAME), a non-selective nitric oxide synthase inhibitor, was studied. In the last group, vasodilation response to sodium nitroprusside (an endothelium-independent vasorelaxant) was evaluated. Clonidine caused vasodilation in a dose-dependent manner by acting on endothelial alpha2-adrenoceptors since its effect was antagonized by yohimbine, and this vasodilation was through the L-arginine pathway since there was no response in the presence of L-NAME in the perfusate. Compared to sham-operated rats, there was a significant right shift in the clonidine concentration curves of cholestatic animals. Maximum response in cholestatic rats was significantly lower comparing to the sham group (P<0.01) and the dose of clonidine that causes 50% of maximum response (ED50) was significantly higher in cholestatic rats (P<0.05). Vasodilation response to sodium nitroprusside was the same in cholestatic and sham-operated rats. Seven-day treatment with aminoguanidine recovered the effect of cholestasis. Seven-day treatment with naltrexone caused an increase in maximum response (P<0.01) and a decrease in ED50 (P<0.05) in cholestatic rats, while this treatment in sham-operated rats caused a decrease in the maximum response (P<0.01) and an increase in ED50 (P<0.05). This study showed that cholestasis is associated with decreased responsiveness of mesenteric vascular bed to clonidine and the cholestasis-associated NO overproduction and increased level of endogenous opioids may contribute to this process.
 ...
PMID:alpha2-Adrenoceptor subsensitivity in mesenteric vascular bed of cholestatic rats: the role of nitric oxide and endogenous opioids. 1591 Aug 5

In rat aorta, the presence of functional alpha(2)-adrenoceptors (alpha(2)-AR) was investigated in ring preparations preconstricted with alpha(1)-adrenergic and non- alpha(1)-adrenergic agonists. Particularly, the hypothetical interference of alpha(2)-AR agonists with alpha(1)-AR-mediated vasoconstriction was evaluated. Relaxant and contractile responses to alpha(2)-AR agonists were obtained. In endothelium-intact and endothelium-denuded aortic rings preconstricted with phenylephrine (1 x 10(-6) m), the imidazoline derivatives, clonidine and UK14304, induced relaxations with similar order of potencies (-log EC(50)) and maxima relaxant effects respectively. Pretreatment with the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) had no effect on the relaxant responses to clonidine and UK14304. In phenylephrine-constricted rings with endothelium, relaxations to clonidine and UK 14304 were not antagonized by the selective alpha(2)-AR antagonist, rauwolscine (< or =1 x 10(-6) m). Clonidine and UK 14304 induced only contractions on endothelium-intact and endothelium-denuded aortic rings contracted with prostaglandin F(2alpha) (3 x 10(-7) m). Moreover, clonidine and UK 14304-induced relaxation of endothelium-denuded arteries precontracted with methoxamine but not with serotonin. Finally, the concentration-contraction curves to clonidine and UK 14304 in endothelium-denuded aortic rings were significantly shifted to the right by the alpha(1D)-AR selective antagonist, BMY 7378, and rauwolscine. The pA(2) and pK(B) values for BMY 7378 and rauwolscine, respectively, against endothelium-independent actions of clonidine and UK 14304 were characteristic of an effect on the alpha(1D)-AR. The other selective alpha(2)-AR agonist tested BHT 933 (an azepine derivative), lacks considerable relaxant and contractile effects in rat aorta. The results provide no evidence for the presence of functional alpha(2)-AR in rat aorta. Respectively, the relaxant and contractile effects of the imidazoline derivatives, clonidine and UK 14304, may be due to an adjustable (in relation to the agonist-dependent active state of the alpha(1)-AR), inhibitory and excitatory, interaction with alpha(1)-ARs.
 ...
PMID:Evidence against alpha-adrenoceptors mediating relaxation in rat thoracic aortae: alpha-agonists relaxation depends on interaction with alpha-adrenoceptors. 1686 17


1 2 Next >>