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)

1. Male, Long Evans rats were chronically instrumented with pulsed Doppler flow probes and intravascular catheters to permit assessment of the regional haemodynamic responses to human and rat adrenomedullin, to compare the responses to human adrenomedullin to those of human alpha-CGRP in the absence and presence of the CGRP1-receptor antagonist, human alpha-CGRP [8-37], and to determine the involvement of nitric oxide (NO)-mediated mechanisms in the responses to human adrenomedullin, relative to human alpha-CGRP. 2. Human and rat adrenomedullin (0.3, 1, and 3 nmol kg-1, i.v.) caused dose-dependent hypotension and tachycardia, accompanied by increases in renal, mesenteric and hindquarters flows and vascular conductances. At the lowest dose only, the hypotensive and mesenteric vasodilator effects of rat adrenomedullin were significantly greater than those of human adrenomedullin. 3. Human alpha-CGRP at a dose of 1 nmol kg-1 caused hypotension, tachycardia and increases in hindquarters flow and vascular conductance, but reduction in renal and mesenteric flows, and only transient vasodilatations in these vascular beds. These effects were substantially inhibited by human alpha-CGRP [8-37] (100 nmol kg-1 min-1), but those of human adrenomedullin (1 nmol kg-1) were not; indeed, the mesenteric haemodynamic effects of the latter peptide were enhanced by the CGRP1-receptor antagonist. 4. In the presence of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 183 nmol kg-1 min-1), there was only a slight, but significant, inhibition of the hindquarters hyperaemic vasodilator effect of human adrenomedullin, but not that of human alpha-CGRP. 5. These results indicate that the marked regional vasodilator effects of human (and rat) adrenomedullin are largely independent of NO and, in vivo, do not involve CGRP1-receptors.
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PMID:Regional haemodynamic effects of human and rat adrenomedullin in conscious rats. 773 84

Responses to synthetic human adrenomedullin (ADM), a novel hypotensive peptide recently discovered in human pheochromocytoma cells, and calcitonin gene-related peptide (CGRP), a structurally related peptide, were investigated in the hindquarters vascular bed of the rat. Under conditions of controlled hindquarters blood flow, intraarterial injections of ADM (0.01-0.3 nmol) and of CGRP (0.03-0.3 nmol) caused dose-related decreases in hindquarters perfusion pressure and decreases in systemic arterial pressure. Following administration of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), hindquarters vasodilator and systemic depressor responses to ADM were significantly decreased, whereas L-NAME did not significantly decrease the vasodilator response to CGRP in either the hindquarters or systemic vascular beds. Following administration of the cyclooxygenase inhibitor, meclofenamate, vasodilator responses to ADM and to CGRP were not significantly decreased. When the relative vasodilator activity of the two peptides was compared on a nmol basis, responses to ADM were similar to responses with CGRP in the hindquarters vascular bed, whereas ADM was 30-100 fold less potent than CGRP in decreasing systemic arterial pressure. The present data demonstrate that ADM has significant vasodilator activity in the hindquarters vascular bed of the rat, that hindquarters vasodilator and systemic vasodepressor responses to ADM, but not to CGRP, are dependent upon the release of nitric oxide from the endothelium.
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PMID:L-NAME modulates responses to adrenomedullin in the hindquarters vascular bed of the rat. 796 46

Hypoxia decreases vasorelaxation and leads to pulmonary arterial hypertension. A newly identified 52 amino-acid peptide adrenomedullin (ADM) exerts vasodilator effect in intact animals under normoxic condition. We studied the effect of human ADM on rat pulmonary arterial and aortic rings under normoxic and hypoxic conditions. During normoxia, ADM caused a concentration-dependent relaxation of precontracted aortic and pulmonary arterial rings; the relaxation was much more pronounced in pulmonary arterial rings and was abolished by the nitric oxide (NO) synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) and by deendothelialization. A fragment of ADM, ADM13-52, caused a degree of relaxation similar to that induced by ADM in pulmonary arterial rings, but not in the aortic rings, and the relaxation of pulmonary artery caused by ADM13-52 was not affected by the cyclooxygenase inhibitor indomethacin but was abolished by L-NAME and by deendothelialization. During hypoxia, ADM13-52 failed to relax pulmonary arterial rings, whereas ADM caused modest relaxation of pulmonary arterial rings (one third of the relaxation during normoxia), which was abolished by pretreatment with indomethacin. Our results indicate that the vasorelaxant effect of ADM is more pronounced in pulmonary artery than in the aorta; ADM has more potent vasodilator effect than ADM13-52 during hypoxia; ADM relaxes hypoxic pulmonary artery through an indomethacin-sensitive pathway; amino acids 1-12 in ADM must be present for relaxation of chronic hypoxic pulmonary arterial rings; and last, the presence of endothelium is necessary for the expression of ADM-mediated relaxation.
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PMID:Adrenomedullin dilates rat pulmonary artery rings during hypoxia: role of nitric oxide and vasodilator prostaglandins. 887 94

Responses to and the mechanism of action of adrenomedullin (ADM), the carboxy-terminal fragments of ADM, and calcitonin gene-related peptide (CGRP), a structurally related peptide, were investigated in the pulmonary vascular bed of the rat. Under conditions of elevated tone and controlled pulmonary blood flow in the isolated blood-perfused rat lung, injections of ADM, the 15-52 amino acid carboxy-terminal ADM analogue (ADM15-52), and CGRP caused dose-related decreases in pulmonary arterial perfusion pressure. In contrast, the carboxy-terminal 22-52 and 40-52 amino acid fragments had no consistent vasodilator activity. After administration of the nitric oxide synthase inhibitors, N omega-nitro-L-arginine benzyl ester or N omega-nitro-L-arginine methyl ester (L-NAME), pulmonary vasodilator responses to ADM, to ADM15-52, to CGRP, to acetylcholine, and to bradykinin were significantly decreased in the rat, whereas vasodilator responses to isoproterenol and nitroglycerin were not changed. However, in the pulmonary vascular bed of the cat, L-NAME had no significant effect on vasodilator responses to ADM in doses that attenuated vasodilator responses to acetylcholine and bradykinin. L-NAME had no effect on responses to isoproterenol or nitric oxide. When the relative vasodilator activity of the active peptides was compared, ADM15-52 was approximately three-fold less potent than ADM, and ADM was threefold less potent than CGRP in decreasing pulmonary vascular resistance in the rat lung. When vasodilator responses were compared in the rat and cat, ADM was threefold more potent in decreasing pulmonary vascular vascular resistance in the cat than in the rat, and vasodilator responses to ADM were independent of the intervention used to raise tone in the rat. The present data demonstrate that ADM and ADM15-52 have significant vasodilator activity in the pulmonary vascular bed of the rat, and that responses to ADM, ADM15-52, and CGRP are dependent on the release of nitric oxide in the rat. The present results indicate that pulmonary vasodilator responses to ADM are not dependent on the release of nitric oxide in the cat and suggest that responses to the peptide are mediated by different mechanisms in the pulmonary vascular bed of the rat and cat.
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PMID:Pulmonary vasodilator responses to adrenomedullin are reduced by NOS inhibitors in rats but not in cats. 896 12

The purpose of the present study was to investigate the effects of intracavernosal injections of adrenomedullin (ADM) and calcitonin gene-related peptide (CGRP), two structurally similar peptides, on penile erection in the anesthetized cat. Erectile responses to ADM and CGRP were compared with responses to a standard drug combination (1.65 mg papaverine, 25 microg phentolamine, and 0.5 microg prostaglandin E1 [PGE1]). Intracavernosal injections of ADM (0.1-3 nmol) and CGRP (0.01-0.3 nmol) induced erection in a dose-dependent manner. The maximal increase in intracavernosal pressure in response to ADM was a 75% increase, while the maximal response to CGRP was comparable to that induced by the reference combination, and the maximal increase in penile length was comparable with ADM, CGRP, and the standard drug combination. The duration of the maximal pressure increase and the total duration of the response to ADM and CGRP were more abbreviated than with the control combination, and systemic blood pressure was reduced significantly after administration of CGRP, the control combination, and the higher doses of ADM. The nitric oxide synthase inhibitor, L-NAME, and the K+(ATP)-channel antagonist, glybenclamide, had no effect on the erectile response to CGRP or ADM. The CGRP receptor antagonist CGRP(8-37) attenuated the erectile response to CGRP but not to ADM. These data suggest that the erectile responses to ADM and CGRP are not mediated by nitric oxide release or the opening of K+(ATP) channels, two mechanisms reported to be involved in penile erection, and that CGRP and ADM induce penile erection by activating different receptors.
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PMID:Comparison of responses to adrenomedullin and calcitonin gene-related peptide in the feline erection model. 934 49

A novel cardiac catheterization technique was devised to investigate the pulmonary arterial pressure-blood flow relationship in intact spontaneously breathing rats (ISBR) under physiological conditions with constant left atrial pressure and controlled blood flow within the normal range. Observations using this new technique in vivo were contrasted with data derived with isolated perfused rat lungs in vitro. Unlike results in in vitro isolated perfused rat lungs, the pressure-flow curves in vivo were curvilinear, with pulmonary artery pressure increasing more rapidly at low pulmonary blood flows of 4-8 ml/min and less rapidly at higher flow rates. Pressure-flow curves were reproducible and were not altered by 1-1.5 h of arrested perfusion, cyclooxygenase blockade, or perfusion with aortic or mixed venous blood. In contrast to results in in vitro isolated perfused rat lungs, NG-nitro-L-arginine methyl ester (L-NAME) increased pulmonary arterial pressure at all but the lowest flow rates with a slight effect on the curvilinear pressure-flow relationship. L-NAME reversed pulmonary vasodilator responses to acetylcholine and bradykinin and enhanced the pulmonary vasodilator response to nitroglycerin. The present data suggest that actively induced pulmonary hypertension is under greater control by endothelium-derived relaxing factor (EDRF). Unlike previous results in in vitro perfused rat lungs, results in ISBR demonstrate that the pulmonary vasodilator response to adrenomedullin-(13-52) is not mediated by calcitonin gene-related peptide receptors, which are not coupled to the release of EDRF. These results indicate that this novel technique may provide a useful model for the study of the pulmonary circulation in the intact chest rat.
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PMID:Novel catheterization technique for the in vivo measurement of pulmonary vascular responses in rats. 957 25

The effects of human adrenomedullin-(13-52) [hADM-(13-52)] were investigated in the rat pulmonary vascular bed and in isolated rings from the rat pulmonary artery (PA). Under conditions of controlled blood flow and constant left atrial pressure when tone was increased with U-46619, injection of hADM-(13-52) produced dose-related decreases in lobar arterial pressure. Pulmonary vasodilator responses in the intact rat and vasorelaxant responses to hADM-(13-52) in rat PA rings were inhibited by NG-nitro-L-arginine methyl ester (L-NAME) and L-N5-(1-iminoethyl)-ornithine hydrochloride (L-NIO). Vasorelaxant responses to hADM-(13-52) were also inhibited by methylene blue, endothelium removal, hADM-(26-52), and iberiotoxin, whereas meclofenamate, calcitonin gene-related peptide-(8-37) [CGRP-(8-37)], glibenclamide, and apamin were without effect. Because vasorelaxant responses to NS-1619, a large-conductance Ca(2+)-activated K+ channel agonist, were not altered by L-NAME and vasorelaxant responses to acetylcholine and CGRP were not altered by hADM-(26-52), the present data suggest that ADM-(13-52) acts on a receptor in the pulmonary vascular bed that is coupled to endothelial nitric oxide release. These data suggest that this nitric oxide release may lead to guanosine 3',5'-cyclic monophosphate-dependent K+ channel activation, which produces a pulmonary vasorelaxant response through hyperpolarization of vascular smooth muscle cells. The present data suggest that ADM-(13-52) modulates receptor-mediated, but not voltage-dependent, pulmonary vascular contraction by influencing Ca2+ influx. These results suggest that the ADM fragment, hADM-(13-52), acts as an endothelium-dependent vasodilator agent in the pulmonary vascular bed of the rat.
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PMID:Analysis of responses to adrenomedullin-(13-52) in the pulmonary vascular bed of rats. 957 29

We have recently shown that endomorphin 1, an endogenous ligand for the mu-opioid receptor, and nociceptin (Orphanin FQ; OFQ), an endogenous ligand for the ORL1 receptor, have substantial vasodilator activity in the hindquarters vascular bed of the rat. In the present study, the role of nitric oxide, vasodilator prostaglandins, and the opening of K+ ATP channels in mediating vasodilator responses to endomorphin 1, PL017, and DAMGO was investigated in the regional vascular bed in the rat. Under constant-flow conditions, injections of the mu-selective agonists endomorphin 1, PL017 ([N-MePhe3,D-Pro4]-morphiceptin), and DAMGO, and the ORL1 receptor agonist nociceptin/ OFQ produced dose-dependent decreases in hindquarters perfusion pressure. Vasodilator responses to endomorphin 1, PL017, and DAMGO, and the endothelium-dependent vasodilators acetylcholine and adrenomedullin were attenuated by the nitric oxide synthase inhibitor L-NAME (50 mg/kg IV) at a time when vasodilator responses to nociceptin/OFQ were not altered. Vasodilator responses to isoproterenol and prostaglandin E1, agents known to increase cAMP levels, and the nitric oxide donor DEA/NO were not altered by the nitric oxide synthase inhibitor. Responses to endomorphin 1, PL017, DAMGO, and nociceptin/OFQ were not altered by sodium meclofenamate at a time when vasodilator responses to arachidonic acid were reduced significantly or after administration of U-37883A at a time when vasodilator responses to levcromakalim were reduced significantly. The results of these studies indicate that responses to endomorphin 1, PL017, and DAMGO are mediated in large part by the release of nitric oxide, while responses to nociceptin/OFQ are mediated by an L-NAME-insensitive mechanism. Moreover, these results demonstrate that responses to these peptides are not mediated by the release of vasodilator prostaglandins or the opening of K+ATP channels the hindquarters vascular bed.
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PMID:Nitric oxide release mediates vasodilator responses to endomorphin 1 but not nociceptin/OFQ in the hindquarters vascular bed of the rat. 986 68

We examined the effect of adrenomedullin on the cardiovascular system of an animal model for preeclampsia. An inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester (L-NAME), was infused subcutaneously into rats at a constant rate from day 14 of pregnancy to make an animal model for preeclampsia. Adrenomedullin was continuously infused intravenously at a dose of 3 or 10 pmol/h from day 17 of pregnancy. The basal systolic blood pressure was significantly higher in the L-NAME treated rats than in the control rats. The adrenomedullin administration at day 19 of pregnancy showed a significant decrease in the blood pressure in the L-NAME treated rats than in vehicle rats during infusion. The blood pressure of normal pregnant rats did not significantly decrease by adrenomedullin infusion. The adrenomedullin decreased pup mortality of the L-NAME treated rats. Adrenomedullin attenuated the L-NAME induced hypertension and pup mortality. On the other hand, adrenomedullin administration in both pregnant rats in early gestation (5-11 days of pregnancy) and in non-pregnant rats did not show any significant effect on L-NAME-induced hypertension. The adrenomedullin mRNA level was predominantly expressed at high levels in the ovary, uterus and placenta, but at low levels in other tissues in pregnant rats in late gestation. The adrenomedullin mRNA level of the L-NAME treated rats in placenta decreased more than in the normal pregnant rats in late gestation (P < 0.05). These findings suggest that the adrenomedullin might play an important role in the regulation of the cardiovascular system of the mother and fetoplacental unit in rats.
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PMID:Adrenomedullin attenuates the hypertension in hypertensive pregnant rats induced by N(G)-nitro-L-arginine methyl ester. 1035 53

We characterize herein the impact of myocardial nitric oxide (NO) synthesis on the inotropic response to two cardioactive peptides, endothelin-1 (ET-1) and adrenomedullin (AM). In the isolated perfused rat heart preparation, intracoronary infusion of AM (0.03 and 1 nmol/l) and ET-1 (0.08 and 1 nmol/l) for 30 min induced a dose-dependent, gradual increase in developed tension, the maximal responses being equal. Inhibition of myocardial NO synthase (NOS) by N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 micromol/l) enhanced the inotropic response to ET-1 at a concentration of 1 nmol/l; meanwhile, the effect of AM was not augmented significantly. The inotropic response to simultaneous administration of low, equipotent doses of AM (0.03 nmol/l) and ET-1 (0.08 nmol/l) was significantly smaller than that of either peptide alone. This depressed response was more than overcome by concomitant administration of L-NAME. In conclusion, this study reveals that the maximal inotropic response to ET-1 can be augmented by inhibition of myocardial NOS, whereas it has only a minor impact on the effect of AM. The inotropic response to combined administration of low doses of AM and ET-1 is substantially suppressed by endogenous NO, whereas the individual effects of the peptides at these doses are not the subject of secondary modulation by NO.
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PMID:Impact of NO on ET-1- and AM-induced inotropic responses: potentiation by combined administration. 1093 47


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