scholarly journals Mechanism of Acitretin-Induced Relaxations in Isolated Rat Thoracic Aorta Preparations

2021 ◽  
Author(s):  
Oğuzhan Ekin Efe ◽  
Tolga Reşat Aydos ◽  
Selda Emre Aydingoz
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Potassium Channels ◽  
Vascular Smooth Muscle ◽  
Thoracic Aorta ◽  
Guanylyl Cyclase ◽  
Guanosine Monophosphate ◽  
Sprague Dawley ◽  
Smooth Muscle Contractility ◽  
Relaxation Responses

Acitretin is a member of vitamin A-derived retinoids and its effect on vascular smooth muscle had not been studied yet. The aim of this study is to investigate the effect of acitretin, a retinoid, on vascular smooth muscle contractility. Thoracic aorta preparations obtained from 34 male Sprague-Dawley rats (355 ± 15 g) were studied in isolated organ baths containing Krebs-Henseleit solution. The relaxation responses were obtained with acitretin (10-12‒10-4 M) in endothelium-preserved and endothelium-denuded aorta preparations precontracted with submaximal concentration of phenylephrine. The roles of retinoic acid receptor (RAR), nitric oxide, adenylyl and guanylyl cyclase enzymes, and potassium channels in these relaxation responses were investigated. Acitretin produced concentration-dependent relaxations, which were independent of its solvent dimethylsulfoxide, in endothelium-denuded phenylephrine-precontracted thoracic aorta preparations. While incubation with the RAR antagonist (AGN193109, 10-5 M) had no effect on these relaxations; nitric oxide synthase inhibitor (L-NAME, 10-4 M), adenylyl cyclase inhibitor (SQ2253, 10-5 M), guanylyl cyclase inhibitor (ODQ, 10-6 M), and potassium channel blocker (tetraethylammonium-TEA, 10-2 M) significantly eliminated the relaxation responses induced by acitretin. Acitretin induces relaxation in rat isolated thoracic aorta preparations without endothelium, which may be mediated by nitric oxide, cyclic adenosine monophosphate and cyclic guanosine monophosphate-dependent kinases and potassium channels.

Nitric oxide and regulation of vascular tone: pharmacological and physiological considerations

1998 ◽  
Vol 7 (2) ◽  
pp. 131-140 ◽  
Author(s):  
J McHugh ◽  
DJ Cheek
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular System ◽  
Biological Activities ◽  
Vascular Diseases ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Physical Stimuli ◽  
Artery Disease

The endothelial cells of the vascular system are responsible for many biological activities that maintain vascular homeostasis. Responding to a variety of chemical and physical stimuli, the endothelium elaborates a host of vasoactive agents. One of these agents, endothelium-derived relaxing factor, now accepted as nitric oxide, influences both cellular constituents of the blood and vascular smooth muscle. A principal intracellular target for nitric oxide is guanylate cyclase, which, when activated, increases the intracellular concentration of cyclic guanosine monophosphate, which in turn activates protein kinase G. Acting by this pathway, nitric oxide induces relaxation of vascular smooth muscle and inhibits platelet activation and aggregation. Derangements in endothelial production of nitric oxide are implicated as both cause and consequence of vascular diseases, including hypertension, atherosclerosis, and coronary artery disease.

TNF-alpha and IFN-gamma induce expression of nitric oxide synthase in cultured rat medullary interstitial cells

1995 ◽  
Vol 269 (2) ◽  
pp. F212-F217 ◽  
Author(s):  
K. S. Lau ◽  
O. Nakashima ◽  
G. R. Aalund ◽  
L. Hogarth ◽  
K. Ujiie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Nitric Oxide Synthase ◽  
Vascular Smooth Muscle ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Tnf Alpha ◽  
No Production ◽  
Ifn Gamma ◽  
Oxide Synthase

Cytokines increase the expression of the inducible (type II) nitric oxide synthase (NOS) in macrophages, liver, and renal epithelial cells. Previously, we found that cultured rat medullary interstitial cells (RMIC) contain high levels of soluble guanylyl cyclase. To determine whether these cells can also produce NO, we studied the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on NO production, NOS II mRNA, and NOS II protein expression. Both TNF-alpha and IFN-gamma, in the presence of a low concentration of the other cytokine, caused dose-dependent increases in NO production. Exposure to TNF-alpha and IFN-gamma stimulated the production of NOS II mRNA, as determined by Northern blotting. Restriction mapping of reverse transcription-polymerase chain reaction products indicated that normal cells contained macrophage NOS II, whereas cytokine-stimulated cells contained primarily vascular smooth muscle NOS II and some macrophage NOS II. The appearance of NOS II protein was demonstrated by Western blotting. RMIC cell guanosine 3',5'-cyclic monophosphate accumulation increased 129-fold in response to the cytokines. NOS inhibitors decreased nitrite production. We conclude that 1) TNF-alpha and IFN-gamma induce the expression of vascular smooth muscle NOS II and production of NO in RMIC, and 2) NO acts as an autocrine activator of the soluble guanylyl cyclase in RMIC.

scholarly journals The phytoestrogen ginsensoside Re activates potassium channels of vascular smooth muscle cells through PI3K/Akt and nitric oxide pathways

2007 ◽  
Vol 54 (3,4) ◽  
pp. 381-384 ◽  
Author(s):  
Yutaka Nakaya ◽  
Kazuaki Mawatari ◽  
Akira Takahashi ◽  
Nagakatsu Harada ◽  
Akiko Hata ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Potassium Channels ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells

Investigation of the role of the NO–cGMP pathway on YC-1 and DEA/NO effects on thoracic aorta smooth muscle responses in a rat preeclampsia model

2013 ◽  
Vol 91 (10) ◽  
pp. 797-803 ◽  
Author(s):  
Nergiz Hacer Turgut ◽  
Tijen Kaya Temiz ◽  
Bülent Turgut ◽  
Baris Karadas ◽  
Mesut Parlak ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Thoracic Aorta ◽  
Soluble Guanylate Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Control Group ◽  
Pregnant Rats ◽  
No Donor ◽  
Relaxation Responses ◽  
Muscle Responses

The present study was designed to investigate the effects of YC-1, a nitric oxide (NO)-independent soluble guanylate cyclase (sGC) activator, and DEA/NO, a NO donor, on smooth muscle responses in the preeclampsia model with suramin-treated rats and on the levels of cyclic guanosine monophosphate (cGMP) of thoracic aorta rings isolated from term-pregnant rats. Rats of 2 groups, control group and suramin group, were given intraperitoneal injection of saline or suramin, respectively. Suramin injection caused increased blood pressure, protein in urine, and fetal growth retardation. Thoracic aorta rings were exposed to contractile and relaxant agents. KCl contraction and papaverine relaxation responses were similar. Relaxation responses of YC-1 and DEA/NO decreased in suramin group. In both groups in the presence of ODQ, a sGC inhibitor, the relaxation responses of YC-1 and DEA/NO decreased. The cGMP content was determined by radioimmunoassay technique. The content of cGMP in the suramin group decreased. In the presence of YC-1 and DEA/NO in both groups, cGMP content increased, but in ODQ-added groups, there was a significant decrease. We conclude that in preeclampsia, the decrease of relaxation responses and the decrease of cGMP content could be due to the reduction in stimulation of sGC and the decrease in cGMP levels.

Endothelial ATP-sensitive potassium channels mediate coronary microvascular dilation to hyperosmolarity

1997 ◽  
Vol 273 (1) ◽  
pp. H104-H112 ◽  
Author(s):  
H. Ishizaka ◽  
L. Kuo
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Potassium Channels ◽  
Vascular Smooth Muscle ◽  
Arterial Occlusion ◽  
Katp Channels ◽  
Inward Rectifier Potassium Channels ◽  
Kca Channels ◽  
Cytochrome P 450 ◽  
Coronary Arterioles

Coronary arterial occlusion has been shown to increase osmolarity in the myocardial interstitium. Intracoronary injection of hyperosmolar solutions reduces coronary vascular resistance. However, the response of coronary microvessels to an abluminal increase in osmolarity is unclear, and the underlying mechanism for its vasomotor regulation has not been elucidated. In this regard, porcine coronary arterioles (81 +/- 2 microns) were isolated, cannulated, and pressurized for in vitro study. Hyperosmolarity (300-345 mosM) was produced by adding D-glucose or D-sucrose to the extravascular solution. After the arterioles developed a stable vascular tone, a graded vasodilation was observed when glucose or sucrose was incrementally administered. This hyperosmotic vasodilation was abolished after endothelial removal. Intraluminal administration of KCl (80 mM) or the ATP-sensitive potassium (KATP)-channel inhibitor glibenclamide (1 microM) to the intact vessels significantly attenuated the hyperosmotic vasodilation. Inhibition of inward rectifier potassium channels by a low concentration of BaCl2 (10 microM) did not affect vasodilation. However, a high concentration of BaCl2 (100 microM), which has been reported to inhibit KATP channels, attenuated the hyperosmotic vasodilation. Iberiotoxin (100 nM), a calcium-activated potassium (KCa)-channel inhibitor had no effect on hyperosmolarity-induced vasodilation. Inhibition of the synthesis of endothelial nitric oxide, prostaglandins, and arachidonic acid metabolites from cytochrome P-450 had no effect on hyperosmotic vasodilation. Furthermore, inhibition of vascular smooth muscle KATP channels and the large- and small-conductance KCa channels by extraluminal administration of glibenclamide, iberiotoxin, and apamin, respectively, did not alter vasodilation in response to hyperosmolarity. These results indicate that dilation of coronary arterioles in response to hyperosmotic stimulation requires an intact endothelium. However, the response is independent of the release of nitric oxide, prostaglandins, or cytochrome P-450-related endothelium-derived hyperpolarizing factor and is not a result of activation of KATP and KCa channels in vascular smooth muscle. It is suggested that the opening of KATP channels in vascular endothelium and subsequent hyperpolarization of that cell type mediate coronary microvascular dilation in response to hyperosmolarity.

Halothane and Isoflurane Inhibit Endothelium-derived Relaxing Factor-dependent Cyclic Guanosine Monophosphate Accumulation in Endothelial Cell-Vascular Smooth Muscle Co-cultures Independent of an Effect on Guanylyl Cyclase Activation

1995 ◽  
Vol 83 (4) ◽  
pp. 823-834. ◽  
Author(s):  
Roger A. Johns ◽  
Alexandra Tichotsky ◽  
Michael Muro ◽  
James P. Spaeth ◽  
Timothy D. Le Cras ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Endothelial Cell ◽  
Nitric Oxide Synthase ◽  
Vascular Smooth Muscle ◽  
Cyclic Gmp ◽  
Guanylyl Cyclase ◽  
Calcium Ionophore ◽  
Inhalational Anesthetics ◽  
Oxide Synthase

Background Interaction of inhalational anesthetics with the nitric oxide signaling pathway and the mechanism of such effects are controversial. The aim of this study was to clarify the sites and mechanism of inhalational anesthetic interaction with the vascular nitric oxide and guanylyl cyclase signaling pathway. Methods To specifically study the mechanism of anesthetic interaction with the nitric oxide-guanylyl cyclase pathway, cultured vascular smooth muscle and endothelial cell-vascular smooth muscle (EC-VSM) co-culture models were chosen. Monolayer cultures of VSM with or without cultured endothelial cells grown on microcarrier beads were preequilibrated with anesthetic and stimulated with agonists. The effect of inhalational anesthetics on cyclic guanosine monophosphate (GMP) content of unstimulated VSM and of VSM in which soluble guanylyl cyclase had been activated by the endothelium-independent nitrovasodilators, sodium nitroprusside, nitroglycerin, or nitric oxide was determined. Experiments were also performed to assess the effect of inhalational anesthetics on unstimulated endothelial cell-vascular smooth muscle co-cultures and on co-cultures in which nitric oxide synthase and subsequent cyclic GMP production had been activated by the receptor-mediated agonists bradykinin and adenosine triphosphate and by the non-receptor-mediated calcium ionophore A23187. Results Increasing concentrations of halothane and isoflurane from 0.5 to 5% had no effect on basal cyclic GMP concentrations in cultured VSM alone or in endothelial cell-vascular smooth muscle co-cultures, and had no effect on sodium nitroprusside, nitroglycerin, or nitric oxide stimulated cyclic GMP accumulation in cultured VSM. In agonist-stimulated co-cultures, however, halothane and isoflurane significantly (P < 0.05) inhibited increases in cyclic GMP concentration in response to both receptor- and non-receptor-mediated nitric oxide synthase activating agents. Conclusions Inhalational anesthetics do not stimulate or inhibit basal cyclic GMP production in co-cultures or VSM, suggesting that inhalational anesthetics do not activate soluble or particulate guanylyl cyclase and do not activate nitric oxide synthase. Inhalational anesthetics do not inhibit nitrovasodilator-induced cyclic GMP formation, suggesting a lack of interference with soluble guanylyl cyclase activation. Inhalational anesthetics inhibit both agonist and calcium ionophore-stimulated nitric oxide-dependent cyclic GMP accumulation in endothelial cell-vascular smooth muscle co-cultures. Consistent with previous vascular ring studies, anesthetics appear to inhibit nitric oxide-guanylyl cyclase signaling distal to receptor activation in the endothelial cell and proximal to nitric oxide activation of guanylyl cyclase.

Impairment of intracerebral arteriole dilation responses after subarachnoid hemorrhage

2009 ◽  
Vol 111 (5) ◽  
pp. 1008-1013 ◽  
Author(s):  
Ik-Seong Park ◽  
Joseph R. Meno ◽  
Cordelie E. Witt ◽  
Abhineet Chowdhary ◽  
Thien-Son Nguyen ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Vascular Smooth Muscle ◽  
Time Course ◽  
Vascular Reactivity ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Sprague Dawley ◽  
Luminal Perfusion ◽  
And Control

Object Cerebrovascular dysfunction after subarachnoid hemorrhage (SAH) may contribute to ischemia, but little is known about the contribution of intracerebral arterioles. In this study, the authors tested the hypothesis that SAH inhibits the vascular reactivity of intracerebral arterioles and documented the time course of this dysfunction. Methods Subarachnoid hemorrhage was induced using an endovascular filament model in halothane-anesthetized male Sprague-Dawley rats. Penetrating intracerebral arterioles were harvested 2, 4, 7, or 14 days postinsult, cannulated using a micropipette system that allowed luminal perfusion and control of luminal pressure, and evaluated for reactivity to vasodilator agents. Results Spontaneous tone developed in all pressurized (60 mm Hg) intracerebral arterioles harvested in this study (from 66 rats), with similar results in the sham and SAH groups. Subarachnoid hemorrhage did not affect dilation responses to acidic pH (6.8) but led to a persistent impairment of endothelium-dependent dilation responses to adenosine triphosphate (p < 0.01), as well as a transient attenuation (p < 0.05) of vascular smooth muscle–dependent dilation responses to adenosine, sodium nitroprusside, and 8-Br-cyclic guanosine monophosphate (cGMP). Impairment of NO-mediated dilation was more sustained than adenosine- and 8-Br-cGMP–induced responses (up to 7 days postinsult compared with 2 days). All smooth muscle–dependent responses returned to sham levels by 14 days after SAH. Conclusions Subarachnoid hemorrhage led to a persistent impairment of endothelium-dependent dilation and a transient attenuation of vascular smooth muscle–dependent dilation responses to adenosine. Impairment of NOmediated dilation occurred when the response to cGMP was intact, suggesting a change in cGMP levels rather than an alteration in intracellular mechanisms downstream from cGMP.

Nitric oxide pathway counteracts enhanced contraction to membrane depolarization in aortic rings of rats on high-sodium diet

2007 ◽  
Vol 292 (4) ◽  
pp. R1557-R1562 ◽  
Author(s):  
Magali Cordaillat ◽  
Aurélie Fort ◽  
Anne Virsolvy ◽  
Jean-Luc Elghozi ◽  
Sylvain Richard ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Arterial Pressure ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Membrane Depolarization ◽  
Guanosine Monophosphate ◽  
Sodium Diet

Vascular smooth muscle cell contraction and endothelium-dependent relaxation was evaluated in aortic rings isolated from weaned, 5-mo-old Sprague-Dawley rats fed a normal (NS; 0.8% NaCl) or high (HS; 8% NaCl) sodium diet. Arterial pressure was 140 ± 6 (NS) and 145 ± 6 mmHg (HS). In endothelium-denuded rings, the response to phenylephrine (PE) was not modified by the sodium diet, while that of depolarizing agent KCl and intracellular calcium releasing agent caffeine increased in the HS group. When endothelium was preserved, PE-evoked contraction was reduced in both NS and HS groups, the contraction being yet lower in the HS group. This effect was partially obliterated by addition of NG-nitro-l-arginine methyl ester (l-NAME), independently of the sodium diet. Relaxation to ACh in intact rings and to sodium nitroprusside (SNP) and 8-bromoadenosine 3′5′ cyclic guanosine monophosphate (8-BrcGMP) in the absence of endothelium was enhanced in rings isolated from HS rats. In addition, the dose-response curve to 8-BrcGMP was shifted to the right in the presence of iberiotoxin, an inhibitor of large conductance, voltage-dependent, and calcium-sensitive potassium channel (BKCa). However, shift was more marked in rings from HS rats. Present results provide evidence that response of vascular smooth muscle cell to nitric oxide/cGMP-related compounds is increased in HS rings and is associated with a greater activation of the repolarizing BKCa channels. Such changes might counterbalance enhanced contractile response to membrane depolarization and thus participate in maintenance of arterial pressure in the present model of early and long-term HS feeding in rats.

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