scholarly journals Acetylcholine and sodium nitroprusside cause long-term inhibition of EDCF-mediated contractions

2005 ◽  
Vol 289 (6) ◽  
pp. H2434-H2440 ◽  
Author(s):  
Eva H. C. Tang ◽  
Michel Feletou ◽  
Yu Huang ◽  
Ricky Y. K. Man ◽  
Paul M. Vanhoutte
Keyword(s):  
Sodium Nitroprusside ◽  
Spontaneously Hypertensive Rat ◽  
Isometric Force ◽  
Calcium Ionophore ◽  
Soluble Guanylyl Cyclase ◽  
Inhibitory Effect ◽  
Previous Exposure ◽  
Spontaneously Hypertensive ◽  
A 23187

Preliminary studies suggested that previous exposure to acetylcholine (ACh) exerts a delayed inhibition of subsequent contractions mediated by endothelium-derived contracting factor (EDCF). To confirm this long-term inhibitory effect of ACh and to determine whether nitric oxide (NO) mediates the phenomenon, we suspended rings of spontaneously hypertensive rat (SHR) aortas in organ chambers for the recording of isometric force. The rings were incubated in the absence or presence of Nω-nitro-l-arginine methyl ester (l-NAME; inhibitor of NO synthases) or 1 H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ; inhibitor of soluble guanylyl cyclase) before exposure to increasing concentrations of ACh or sodium nitroprusside (SNP) during contractions to phenylephrine. Thereafter, EDCF-mediated contractions to ACh or the calcium ionophore A-23187 were elicited. If the rings were preexposed to ACh or SNP, the subsequent ACh-induced EDCF-mediated contractions were reduced compared with those obtained in rings of the same arteries not previously exposed to either agent. ODQ did not affect the inhibition caused by preexposure to ACh but significantly reduced that caused by preexposure to SNP. Previous exposure to SNP reduced, whereas previous exposure to ACh did not affect, endothelium-dependent contractions to A-23187. Previous exposure to either ACh or SNP did not affect the contractions to the thromboxane mimetic U-46619. Thus ACh and SNP exert delayed inhibition of EDCF-mediated contractions via distinct pathways. The effect of ACh is NO independent and upstream of the increase in calcium concentration that triggers the release of EDCF. The effect of SNP is downstream of the calcium rise and is mainly NO dependent.

Calcium-independent phospholipase A2 plays a key role in the endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat

2010 ◽  
Vol 298 (4) ◽  
pp. H1260-H1266 ◽  
Author(s):  
Michael S. K. Wong ◽  
Ricky Y. K. Man ◽  
Paul M. Vanhoutte
Keyword(s):  
Endothelial Cells ◽  
Mammalian Cells ◽  
Spontaneously Hypertensive Rat ◽  
Calcium Ionophore ◽  
Isometric Tension ◽  
Membrane Phospholipids ◽  
Spontaneously Hypertensive ◽  
A 23187 ◽  
Hypertensive Rat ◽  
Wistar Kyoto

Phospholipase A2 (PLA2), a regulatory enzyme found in most mammalian cells, catalyzes the breakdown of membrane phospholipids to arachidonic acid. There are two major cytosolic types of the enzyme, calcium-dependent (cPLA2) and calcium-independent (iPLA2) PLA2. The present study investigated whether or not iPLA2 plays a role in the endothelium-dependent contractions of the aorta of the spontaneously hypertensive rat and its normotensive counterpart, the Wistar-Kyoto rat. The presence of iPLA2 in the endothelial cells was identified by using immunochemistry and immunoblotting. Aortic rings with and without the endothelium were suspended in organ chambers for isometric tension recording. The production of prostanoids was measured by using enzyme immunoassay kits. iPLA2 was densely distributed in endothelial cells of the aorta of both strains. At 3 × 10−6 M, the selective iPLA2 inhibitor, bromoenol lactone (BEL), abrogated endothelium-dependent contractions induced by acetylcholine but not those evoked by the calcium ionophore A-23187. The effects of BEL were similar in the aortae of Wistar-Kyoto and spontaneously hypertensive rats. The nonselective PLA2 inhibitor quinacrine abolished the contractions triggered by both acetylcholine and A-23187, whereas the store-operated calcium channel inhibitor SKF-96365 prevented only the acetylcholine-induced contraction. The acetylcholine- but not the A-23187-induced release of 6-keto prostaglandin F1α was inhibited by BEL. The release of thromboxane B2 by either acetylcholine or A-23187 was not affected by BEL. In conclusion, iPLA2 plays a substantial role in the generation of endothelium-derived contracting factor evoked by acetylcholine.

scholarly journals Inhibitory effect of valves on endothelium-dependent relaxations to calcium ionophore in canine saphenous vein

2001 ◽  
Vol 280 (2) ◽  
pp. H892-H898 ◽  
Author(s):  
Daihiko Eguchi ◽  
Zvonimir S. Katusic
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylate Cyclase ◽  
Isometric Force ◽  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Nitric Oxide Synthase Inhibitor ◽  
A 23187 ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Endothelium Dependent Relaxation

The present study was designed to evaluate endothelium-dependent relaxation to the calcium ionophore A-23187 in isolated canine saphenous veins. Isometric force recordings and cGMP measurements using isolated veins with and without valves were performed. During contractions to U-46619 (3 × 10−7 M), endothelium-dependent relaxations to A-23187 (10−9–10−6 M) were significantly reduced in rings with valves compared with rings without valves. Endothelial removal abolished A-23187-induced relaxation. Relaxations to forskolin (FK; 10−8–10−5 M) and diethylaminodiazen-1-ium-1,2-dionate; DEA-NONOate, 10−9–10−5 M) were identical in rings with and without valves. In rings without valves, a nitric oxide synthase inhibitor, N G-nitro-l-arginine methyl ester (l-NAME; 3 × 10−4 M), and a cyclooxygenase inhibitor, indomethacin (10−5 M), partially reduced A-23187-induced relaxation. However, in rings with valves,l-NAME had no effect, whereas indomethacin abolished the relaxation to A-23187. A selective soluble guanylate cyclase inhibitor, 1 H-[1,2,4]-oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 3×10−6 M), had no effect on the relaxation to A-23187 in either group. In contrast, ODQ abolished the A-23187-induced increase in cGMP levels, suggesting that relaxation to nitric oxide released by A-23187 is independent of increases in cGMP. These results demonstrate that endothelium-dependent relaxation to A-23187 is reduced in regions of veins with valves compared with relaxation in the nonvalvular venous wall. Lower production of nitric oxide in endothelial cells of valvular segments appears to be a mechanism responsible for reduced reactivity to A-23187.

scholarly journals Selective inhibition by antiflamrnin-2 of thromboxane B2release from isolated and perfused guinea-pig lung

1992 ◽  
Vol 1 (4) ◽  
pp. 251-254
Author(s):  
Lidia Sautebin ◽  
Giuseppe Cirino ◽  
Massimo Di Rosa
Keyword(s):  
Guinea Pig ◽  
Histamine Release ◽  
Calcium Ionophore ◽  
Selective Inhibition ◽  
Inhibitory Effect ◽  
Amino Acid Residues ◽  
A 23187 ◽  
Normal Lungs

Antiflammin-2 (AF2) is a nonapeptide corresponding to the amino acid residues 246–254 of lipocortin-1 showing anti-inflammatory activity both in vitro and in vivo. The effect of AF2 on the thromboxane B2(TXB2) and histamine release from isolated and perfused guinea-pig lungs has been studied. AF-2 (10–100 nM) inhibited leukotriene C4- (LTC4) (3 ng) and antigen-induced (ovalbumin, 1 mg) TXB2release in normal and sensitized lungs, respectively. In contrast AF-2 (100 nM) did not modify TXB2release induced by histamine (5 μg) or bradykinin (5 μg) in normal lungs. Antigen-induced histamine release was not affected by 100 nM AF-2 infusion. When tested in chopped lung fragments AF-2 (0.1–25 μM) did not modify the release of histamine and TXB2induced by antigen (ovalbumin, 10 μg ml−1) or calcium ionophore A 23187 (1 μM). Our results show that the inhibitory effect of AF-2 on TXB2release is selective and depends on the stimulus applied. In this respect AF-2 mimics, at least in part, the actions of both glucocorticoids and lipocortin-1.

Short- and long-term enalapril affect renal medullary hemodynamics in the spontaneously hypertensive rat

1999 ◽  
Vol 276 (1) ◽  
pp. R10-R16 ◽  
Author(s):  
Stephen A. W. Dukacz ◽  
Michael A. Adams ◽  
Robert L. Kline
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Day Treatment ◽  
Ace Inhibition ◽  
Spontaneously Hypertensive ◽  
Short And Long Term ◽  
Pressure Natriuresis ◽  
The Relationship

Long-term angiotensin-converting enzyme (ACE) inhibition in the spontaneously hypertensive rat (SHR) resets pressure natriuresis and shifts the relationship between renal arterial pressure (RAP) and renal interstitial hydrostatic pressure (RIHP) to lower levels of arterial pressure. These effects persist after withdrawal of treatment. The purpose of this study was to determine the effect of short- and long-term ACE inhibition on medullary blood flow (MBF). Enalapril (25 mg ⋅ kg−1 ⋅ day−1in drinking water) was given to male SHR from 4 to 14 wk of age. Four weeks after stopping treatment, we measured MBF over a wide range of RAP using laser-Doppler flowmetry in anesthetized rats. Additional rats, either untreated or previously treated for 10 wk, received 3-day enalapril treatment just before the experiment. MAP (mmHg ± SE) was 178 ± 6 ( n = 8), 134 ± 6 ( n = 8), 138 ± 5 ( n = 9), and 111 ± 6 mmHg ( n = 9) for the untreated, 3 day, 10 wk, and 10 wk + 3 day groups, respectively. Total renal blood flow for the groups receiving 3-day treatment was significantly higher when compared with that in rats with an intact renin-angiotensin system. Three-day treatment had no effect on the relationship between RAP and RIHP, whereas that in rats receiving 10-wk treatment was shifted to lower levels of RAP by ∼30 mmHg. Both 10-wk and 3-day treatment independently increased the slope of the RAP versus MBF relationship at values of RAP > 100 mmHg. The slopes in perfusion units/mmHg were 0.12 ± 0.01 ( n = 8), 0.26 ± 0.01 ( n = 8), 0.27 ± 0.01 ( n = 9), and 0.30 ± 0.02 ( n = 9) for the untreated, 3 day, 10 wk, and 10 wk + 3 day groups, respectively. These results indicate that the effect of short-term and the persistent effect of long-term enalapril alter renal medullary hemodynamics in a way that may contribute to the resetting of the pressure-natriuresis relationship in treated rats.

Abstract 845: Acute irradiation exposure induces long-term cardiac adverse effects in the spontaneously hypertensive rat

2018 ◽  
Author(s):  
Elliot T. Rosen ◽  
Dmitry Kryndushkin ◽  
Baikuntha Aryal ◽  
Yanira Gonzalez ◽  
Leena Chehab ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Spontaneously Hypertensive Rat ◽  
Spontaneously Hypertensive ◽  
Acute Irradiation ◽  
Hypertensive Rat
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