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Endothelium-intact Rings (endothelium-intact + ring)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Role of Endothelium/Nitric Oxide and Cyclic AMP in Isoproterenol Potentiation of 17ß-Estradiol-Mediated Vasorelaxation

JOURNAL OF CARDIAC SURGERY, Issue 6 2002
HY Chan
Estrogen exerts vasorelaxation and cardiac protection via multiple cellular mechanisms. Estrogen modifies vasodilatation induced by certain relaxants such as ß-adrenoceptor agonists. However, little is known whether low concentrations of ß-adrenoceptor agonists would also influence the acute relaxant response to estrogen. The present study was designed to investigate the synergistic interaction between isoproterenol and 17ß-estradiol, and to study the role of endothelium and cyclic AMP-dependent pathway in this interaction. Changes in vessel tone of the isolated rat mesenteric artery rings were measured by force-displacement Grass transducer. In 9,11-dideoxy-11,, 9,-epoxy-methanoprostaglandin F2, - preconstricted endothelium-intact rings, 17ß-estradiol induced concentration-dependent relaxation with pD2 of 5.074 ± 0.043. Pretreatment of endothelium-intact rings with isoproterenol (1-3 × 10 -9 M, 1-h incubation time) significantly enhanced 17,-estradiol-induced relaxation. Longer incubation (2.5 h) did not produce further amplifying effect. This effect was inhibited by Rp-cGMPS triethylamine (3 × 10 -6 M), and disappeared in the presence of 3 × 10 -5 M NG -nitro-L-arginine methyl ester or in the endothelium-denuded rings. The effect of isoproterenol was partially antagonized by propranolol (3 × 10 -6 M), ICI 118,551 (3 × 10 -6 M) but not by atenolol (10 -5 M). None of three ,-adrenoceptor antagonists affected 17ß-estradiol-induced relaxation in the absence of isoproterenol. Rp-cAMPS triethylamine (3 × 10 -6 M) abolished the effect of isoproterenol. Besides, exposure to 3 × 10 -9 M forskolin for 1 h also potentiated the relaxant response to 17,-estradiol. In summary, this isoproterenol enhancement was dependent on the presence of endothelium and abolished by L-NAME via a ,2 -adrenoceptor-mediated cyclic AMP-dependent mechanism. These data also indicate the possible existence of cyclic AMP-dependent nitric oxide-producing pathway in the regulation of the vascular response to vasodilators. (supported by UPGC Direct Grant) [source]

Gender-specific vascular effects elicited by chronic ethanol consumption in rats: a role for inducible nitric oxide synthase

BRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2008
C R Tirapelli
Background and purpose: Epidemiological data suggest that the risk of ethanol-associated cardiovascular disease is greater in men than in women. This study investigates the mechanisms underlying gender-specific vascular effects elicited by chronic ethanol consumption in rats. Experimental approach: Vascular reactivity experiments using standard muscle bath procedures were performed on isolated thoracic aortae from rats. mRNA and protein for inducible NO synthase (iNOS) and for endothelial NOS (eNOS) was assessed by RT-PCR or western blotting, respectively. Key results: In male rats, chronic ethanol consumption enhanced phenylephrine-induced contraction in both endothelium-intact and denuded aortic rings. However, in female rats, chronic ethanol consumption enhanced phenylephrine-induced contraction only in endothelium denuded aortic rings. After pre-incubation of endothelium-intact rings with L -NAME, both male and female ethanol-treated rats showed larger phenylephrine-induced contractions in aortic rings, compared to the control group. Acetylcholine-induced relaxation was not affected by ethanol consumption. The effects of ethanol on responses to phenylephrine were similar in ovariectomized (OVX) and intact (non-OVX) female rats. In the presence of aminoguanidine, but not 7-nitroindazole, the contractions to phenylephrine in rings from ethanol-treated female rats were greater than that found in control tissues in the presence of the inhibitors. mRNA levels for eNOS and iNOS were not altered by ethanol consumption. Ethanol intake reduced eNOS protein levels and increased iNOS protein levels in aorta from female rats. Conclusions and implications: Gender differences in the vascular effects elicited by chronic ethanol consumption were not related to ovarian hormones but seemed to involve the upregulation of iNOS. British Journal of Pharmacology (2008) 153, 468,479; doi:10.1038/sj.bjp.0707589; published online 26 November 2007 [source]

Anandamide-induced relaxation of sheep coronary arteries: the role of the vascular endothelium, arachidonic acid metabolites and potassium channels

BRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2001
J Grainger
The effects of the endocannabinoid, anandamide, and its metabolically stable analogue, methanandamide, on induced tone were examined in sheep coronary artery rings in vitro. In endothelium-intact rings precontracted to the thromboxane A2 mimetic, U46619, anandamide (0.01 , 30 ,M) induced slowly developing concentration-dependent relaxations (pEC50 [negative log of EC50]=6.1±0.1; Rmax [maximum response]=81±4%). Endothelium denudation caused a 10 fold rightward shift of the anandamide concentration-relaxation curve without modifying Rmax. Methanandamide was without effect on U46619-induced tone. The anandamide-induced relaxation was unaffected by the cannabinoid receptor antagonist, SR 141716A (3 ,M), the vanilloid receptor antagonist, capsazepine (3 and 10 ,M) or the nitric oxide synthase inhibitor, L -NAME (100 ,M). The cyclo-oxygenase inhibitor, indomethacin (3 and 10 ,M) and the anandamide amidohydrolase inhibitor, PMSF (70 and 200 ,M), markedly attenuated the anandamide response. The anandamide transport inhibitor, AM 404 (10 and 30 ,M), shifted the anandamide concentration-response curve to the right. Precontraction of endothelium-intact rings with 25 mM KCl attenuated the anandamide-induced relaxations (Rmax=7±7%), as did K+ channel blockade with tetraethylammonium (TEA; 3 ,M) or iberiotoxin (100 nM). Blockade of small conductance, Ca2+ -activated K+ channels, delayed rectifier K+ channels, KATP channels or inward rectifier K+ channels was without effect. These data suggest that the relaxant effects of anandamide in sheep coronary arteries are mediated in part via the endothelium and result from the cellular uptake and conversion of anandamide to a vasodilatory prostanoid. This, in turn, causes vasorelaxation, in part, by opening potassium channels. British Journal of Pharmacology (2001) 134, 1003,1012; doi:10.1038/sj.bjp.0704340 [source]