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  • 1
    Electronic Resource
    Electronic Resource
    Melbourne, Australia : Blackwell Science Asia Pty. Ltd.
    Clinical and experimental pharmacology and physiology 29 (2002), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Endomorphins 1 and 2, endogenous ligands for the μ-opioid receptor, and nociceptin (orphanin FQ; OFQ), an endogenous ligand for the ORL1 receptor, have vasodilator activity in the vascular bed of the hindquarters of the rat. In the present study, the role of nitric oxide (NO), vasodilator prostaglandins and the opening of KATP channels in mediating vasodilator responses to these novel agonists was investigated in the rat.2. Under constant-flow conditions, injections of endomorphins 1 and 2, PL017 ([N-MePhe3,D-Pro4]-morphiceptin), nociceptin and Tyr-D-Ala-Gly-MePhe-Gly(ol)-enkephalin (DAMGO) produced dose-dependent decreases in hindquarters perfusion pressure. Vasodilator responses to endomorphin 1 and 2, acetylcholine and adrenomedullin, were attenuated by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) at a time when vasodilator responses to nociceptin, adrenomedullin and the NO donor diethylamine/NO were not altered.3. Vasodilator responses to endomorphins 1 and 2, nociceptin, PL017 and DAMGO were not altered after administration of 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.4. The results of these studies indicate that vasodilator responses to endomorphins 1 and 2, PL017 and DAMGO are mediated, in large part, by the release of NO, whereas vasodilator responses to nociceptin are mediated by an L-NAME-insensitive mechanism. Moreover, these results demonstrate that the vasodilator responses to these peptides are not due to the release of vasodilator prostaglandins or the opening of KATP channels in the hindquarters vascular bed of the rat.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 231 (1971), S. 263-265 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Fig. 1 Effect of reduced renal pressure on adrenergic responses during infusion of angiotensin. Hind paw perfusion pressure (PP) and systemic blood pressure (AP) are calibrated in mm Hg. The left hand portion shows responses to intra-arterial noradrenaline (50, 100, 200 ng) and sympathetic nerve ...
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1434-0879
    Keywords: Nitroprusside ; Penile erection, feline model ; VIP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The use of vasoactive intestinal peptide (VIP), sodium nitroprusside (SNP), and the reference combination of papaverine, prostaglandin E1, and phentolamine was studied in 22 adult cats. The maximal erectile response (intracavernous pressure, penile length, and rigidity) was produced by intracavernous injection of a combination of 1.65 mg papaverine, 0.5μg PGE1, and 25μg phentolamine. This combination was considered as “control” in order to compare the effect of other agents. VIP and SNP increased the intracavernous pressure and caused erection in a dose-dependent manner with a maximal response obtained with 5μg VIP or 10μg SNP. The duration of peak erection and the total duration of drug effect were significantly shorter with VIP and SNP than with the reference combination (P〈0.01). Epinephrine (30μg) reversed the effects of SNP and significantly shortened the duration of peak action and total effect (P〈0.05). This study supports the use of an in vivo feline model for the evaluation of vasoactive agents and demonstrates that the intracavernous injection of either VIP or SNP can induce penile erection in the adult cat.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1434-0879
    Keywords: Key words Penile erection ; Transurethral ; SNP ; Nitric oxide ; cGMP ; Erectile dysfunction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nitric oxide (NO) is an important mediator in the relaxation of cavernosal smooth muscle. The aim of this study was to investigate the in vivo feline erectile response after transurethral administration of sodium nitroprusside (SNP), a NO donor drug. Erectile responses after administration of transurethral SNP were compared with those elicited by an intracavernosal control triple-drug combination (1.65 mg papaverine, 25 μg phentolamine, and 0.5 μg prostaglandin E1). SNP was administered via a 20-gauge Jelco intravenous catheter in a volume of 200 μl and changes in intracavernosal pressure, penile length, and systemic blood pressure were monitored. The control triple-drug combination was administered via a 30-gauge needle at the end of each experiment to serve as a control reference. Transurethral administration of SNP (1–4 mg) induced penile erection in a dose-dependent manner with minimal changes in systemic blood pressure. The maximum increase in intracavernosal pressure and penile length after transurethral administration of SNP (4 mg) was significantly less than after the intracavernosal injection of the control triple-drug combination (P 〈 0.01). These data suggest that transurethral administration of SNP can induce an erectile response in cats with minimal side effects.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-4919
    Keywords: lung microsomes ; human platelets ; bronchoconstriction ; prostaglandin metabolism ; pulmonary biochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of CGS 13080, a thromboxane (TXA2) synthase inhibitor, on airway responses to arachidonic acid (AA) were investigated in the anesthetized cat. Feline and human lung microsomal fraction exhibited prostaglandin I2 (PGI2, prostacyclin), and TXA2 synthase activities, and human platelet microsomal fractions exhibited TXA2 synthase activity. Cat and human lung microsomal fractions, but not human platelets, exhibited the presence of GSH-dependent PGE2 isomerase activity. CGS 13080 inhibited TXA2 synthase activity in all three microsomal fractions in a concentration-dependent manner. The increases in transpulmonary pressure and lung resistance and decreases in dynamic compliance in response to AA were decreased significantly by CGS 13080. These data suggest that the bronchoconstrictor actions of AA are mediated in large part by the formation of TXA2. The data further indicate that cyclooxygenase products other than TXA2 are involved in the bronchoconstrictor response to AA since meclofenamate had greater inhibitory activity than did CGS 13080. Moreover, the effects of CGS 13080 were due to inhibition of TXA2 synthase rather than an effect on TXA2 receptors, since airway responses to the TXA2 mimic, U46619, were not altered. The present data show that CGS 13080 inhibits TXA2 synthase activity without altering cyclooxygenase, PGI2 synthase, or GSH-dependent PGE2 isomerase activities. The data further indicate that in vivo administration of CGS 13080 may selectively increase PGI2 synthase activity.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 87 (1989), S. 41-46 
    ISSN: 1573-4919
    Keywords: arachidonic acid ; prostaglandin endoperoxide H2 ; ibuprofen ; indomethacin ; meclofenamate ; feline lung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary Previous studies have suggested the possibility that the non-steroidal antiflammatory drug (NSAID), ibuprofen, may inhibit thromboxane (TX) A2 synthase activity in addition to inhibiting cyclooxygenae activity. Microsomal fractions isolated from the cat lung contain cyclooxygenase as well as prostacyclin (PGI2) synthase, TX synthase, and a GSH-dependent prostaglandin (PG) E2 isomerase activities. When [1-14C] PG endoperoxide H2 (PGH2) was used as substrate, ibuprofen, indomethacin, and meclofenamate exhibited differential effects on terminal enzyme activities. Ibuprofen, at concentrations up to 1 mM, had no effect on the activities of PGI2 synthase, TXA2 synthase of GSH-dependent PGE2 isomerase, whereas indomethacin selectively inhibited PGI2 synthase activity at 5 x 10−4 M and 10−3 M. Meclofenamate selectively inhibited TXA2 synthase activity at 5 x 10−4 M and 10−3 M. At concentrations of 5 x 10−3 M, this selectivity was not oberved, and indomethacin and meclofenamate decreased the formation of both 6-keto-PGF1α and TXB2. These data indicate that the choice of NSAID and the concentration employed may specifically alter PGH2 metabolism. This action may affect the physiologic consequences of the exchange of PGH2 between cells. The data further indicate that indomethacin has the potential for use as a tool to specifically attenuate PGI2 synthase activity in vitro.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-4919
    Keywords: endothelin ; thromboxane analog ; saphenous vein ; gastroepiploic artery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of endothelin (ET-1) on smooth muscle contractile activity were investigated and compared in human saphenous vein and gastroepiploic artery, vessels frequently used in revascularization procedures. ET-1 contracted saphenous vein and gastroepiploic artery in a concentration-dependent manner. The peptide produced a greater maximal effect in the vein than in the artery and, in both preparations, ET-1 was less efficacious than U46619, an agent which mimics the actions of thromboxane A2 at the thromboxane A2/prostaglandin HZ receptor. The contractile response to ET-1 declined spontaneously at a more rapid rate in the artery than in the vein. The present data indicate that ET-1 has significant contractile activity in both vessels which are used for coronary arterial bypass surgery and suggest that although, a weaker vasoconstrictor than U46619, the peptide could induce vasospasm in both graft vessels.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-4919
    Keywords: endothelium ; polymorphonuclear leukocyte ; nitric oxide ; intimal hyperplasia ; P-selectin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of an anti-P-selectin monoclonal antibody (MAb, PB1.3; Cytel Corporation) on neoendothelialization; neoendothelial function, as evidenced by acetylcholine-induced relaxation (nitric oxide formation); and intimal hyperplasia following embolectomy catheter-induced injury to the rabbit thoracic aorta were investigated. Catheter injury was induced in two groups of New Zealand White rabbits. One group received no treatment, while the second group received short-term treatment with the MAb (i.p., immediately before and 12 h after induction of catheter injury). A third group underwent a sham operation and served as uninjured controls. Following sacrifice at 2 weeks after injury, aortic rings were assessed for degree of intimal hyperplasia, neoendothelial morphology (scanning electron microscopy), and acetylcholine-induced relaxation. Aortic tissue from catheter-injured animals that received treatment exhibited improved neoendothelial morphology, as compared with tissue from untreated but catheterized animals; however, no statistically significant attenuation of the hyperplastic response or improvement in the attenuated neoendothelial-dependent acetylcholine-induced relaxant response that is characteristic of neoendothelium that forms after catheter denudation was observed. These data suggest that short-term attenuation of P-selectin-mediated polymorphonuclear leukocyte (PMN)/endothelium, PMN/platelet interactions, and/or thrombin formation beneficially affects neoendothelialization of the vascular wall following balloon catheter-induced injury.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-4919
    Keywords: adrenomedullin (ADM) ; calcitonin gene-related peptide (CGRP) ; vasodilation ; nitric oxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Vasodilator responses to human adrenomedullin (hADM), a newly discovered hypotensive peptide, human calcitonin gene-related peptide-α (hCGRP-α) and hCGRP-β, which share structural homology with hADM, were compared in the hindlimb vascular bed of the cat under constant flow conditions. Injections of hADM (0.003-1 nmol), hCGRP-α, and hCGRP-β (0.003-0.3 nmol) into the perfusion circuit caused dose-related decreases in hindlimb perfusion pressure. Vasodilator responses to hCGRP-α and hCGRP-β were similar in potency and duration, and the doses of hCGRP-α and hCGRP-β required to reduce hindlimb perfusion pressure 40 mm Hg (ED40 mm Hg) were significantly lower than the ED40 mm Hg for hADM. The duration of the hindlimb vasodilator responses to hCGRP-α and hCGRP-β were significantly longer than the duration of the response to hADM. Amylin, a peptide that shares structural homology with ADM and with CGRP, had no significant effect on hindlimb perfusion pressure when injected in doses up to 1 nmol. Decreases in hindlimb perfusion pressure in response to hADM, hCGRP-α, and hCGRP-β were not altered by L-N5-(1-iminoethyl)-ornithine (L-NIO) in a dose of the nitric oxide synthase inhibitor that decreased the vasodilator response to acetylcholine or by the cyclooxygenase inhibitor, meclofenamate, in a dose that decreased the vasodilator response to archidonic acid. The present data demonstrate that hADM, hCGRP-α, and hCGRP-β have potent, but relatively short-lasting, vasodilator activity, and that vasodilator responses are not dependent on the release of nitric oxide or vasodilator prostaglandins in the hindlimb vascular bed of the cat.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 201 (1981), S. 513-521 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Nerve terminal-smooth muscle relationships were studied in pulmonary arteries of the cat using 5-hydroxydopamine to help differentiate adrenergic and nonadrenergic terminals. There was a periarterial plexus of nerves in the walls of pulmonary arteries that extended into the lung to innervate even small arteries having a single layer of smooth muscle cells. Adrenergic nerves surrounded all arteries and extended into the tunica media of the large arteries. There were also apparent cholinergic nerves around the pulmonary arteries, although this was confirmed by electron microscopy for medium- and small-sized arteries only. The relationships of nerve terminals to smooth muscle cells in pulmonary arteries suggest that release of norepinephrine by adrenergic terminals can produce both decreased compliance and increased resistance in the pulmonary vascular bed, and that acetylcholine released by cholinergic terminals may act directly on vascular smooth muscle or on adrenergic terminals to modulate release of norepinephrine. These results suggest that both sympathetic and parasympathetic nerves may have a regulatory role in the pulmonary circulation.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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