Altered alpha adrenergic vasoresponsiveness in a non‐cirrhotic portal hypertension model of <i>E. coli</i> injection

Rizvi, Moattar Raza; Omanwar, Swati; Fahim, Mohammad; Sarin, Shiv Kumar

doi:10.1111/j.1440-1746.2006.04440.x

Cited by 6 publications

(5 citation statements)

References 43 publications

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“…Aortic segments were subjected to a tension of 2 g that was readjusted every 15 min during a 60 min equilibration period before drug administration. Vessels were initially exposed to 75 mM KCl to check their functional integrity, and the presence of endothelium was confirmed by the ability of ACh (10 μ M) to relax segments precontracted with phenylephrine (PE) at a concentration that produces close to 50% of the contraction induced by 75 mM KCl [16]. …”

Section: Methodsmentioning

confidence: 99%

Modulation of Vasodilator Response via the Nitric Oxide Pathway after Acute Methyl Mercury Chloride Exposure in Rats

Omanwar

Saidullah

Ravindran

et al. 2013

BioMed Research International

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Mercury exposure induces endothelial dysfunction leading to loss of endothelium-dependent vasorelaxation due to decreased nitric oxide (NO) bioavailability via increased oxidative stress. Our aim was to investigate whether acute treatment with methyl mercury chloride changes the endothelium-dependent vasodilator response and to explore the possible mechanisms behind the observed effects. Wistar rats were treated with methyl mercury chloride (5 mg/kg, po.). The methyl mercury chloride treatment resulted in an increased aortic vasorelaxant response to acetylcholine (ACh). In methyl-mercury-chloride-exposed rats, the % change in vasorelaxant response of ACh in presence of Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME; 10−4 M) was significantly increased, and in presence of glybenclamide (10−5 M), the response was similar to that of untreated rats, indicating the involvement of NO and not of endothelium-derived hyperpolarizing factor (EDHF). In addition, superoxide dismutase (SOD) + catalase treatment increased the NO modulation of vasodilator response in methyl-mercury-chloride-exposed rats. Our results demonstrate an increase in the vascular reactivity to ACh in aorta of rats acutely exposed to methyl mercury chloride. Methyl mercury chloride induces nitric oxide synthase (NOS) and increases the NO production along with inducing oxidative stress without affecting the EDHF pathway.

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Section: Methodsmentioning

confidence: 99%

Modulation of Vasodilator Response via the Nitric Oxide Pathway after Acute Methyl Mercury Chloride Exposure in Rats

Omanwar

Saidullah

Ravindran

et al. 2013

BioMed Research International

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“…Experiments were performed on ring preparations (2–3 mm wide) of rat thoracic aorta, prepared with care in order to keep the endothelium intact. 16 Aortic rings were mounted isometrically under a resting tension of 2 g in an organ bath, between a stationary stainless steel hook and an isometric force transducer (Grass FT-03, USA) and changes in isometric tension were recorded by a Power Lab data–acquisition system (8SP 20B, AD Instruments, Australia) with a computerized analysis programme (Chart 5.4.2, AD Instruments). Vessels were maintained at 37°C in an organ bath containing 10 mL of modified Krebs-bicarbonate buffer solution of the following composition (in m M ): Nacl 118; KCl 4.8; MgSO 4 1.2; KH 2 PO 4 1.2; NaHCO 3 2.5; CaCl 2 2.5 and Glucose 11.0; pH, 7.4, bubbled with 95% O 2 and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Persistence of EDHF pathway and impairment of the nitric oxide pathway after chronic mercury chloride exposure in rats: Mechanisms of endothelial dysfunction

2010

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Chronic mercury exposure impairs vascular function, leading to the depression of endothelium-dependent vasodilatation. Loss of the nitric oxide (NO) pathway has been implicated, but little is known about effects on other endothelial mediators. This study investigated the mechanisms of endothelial dysfunction in rats subjected to chronic mercury chloride exposure. The endothelium-dependent relaxation of rat aorta evoked by acetylcholine (ACh) and isoproterenol was impaired in a dose-dependent manner by chronic mercury chloride exposure. Endothelium-independent responses to sodium nitroprusside (SNP) were not affected by chronic mercury chloride exposure. In healthy vessels, ACh-induced relaxation was inhibited by L-N-nitroarginine methyl ester (L-NAME; 10–4M) and partially by glybenclamide (10–5M), indicating the involvement of NO and endothelium-derived hyperpolarizing factor (EDHF). In vessels from mercury-exposed rats, responses to ACh were insensitive to L-NAME but were significantly reduced by glybenclamide, indicating selective loss of NO-mediated relaxation. In vessels from mercury-exposed rats, responses to ACh were partially restored after treatment with the antioxidant, superoxide dismutase (SOD) and catalase, this effect was not seen when aorta from exposed group was incubated with L-NAME along with SOD and catalase indicating selective loss of NO-mediated vasodilatation and with no affect the EDHF-mediated component of relaxation. The results imply that chronic mercury exposure selectively impairs the NO pathway as a consequence of oxidative stress, while EDHF is able to maintain endothelium-dependent relaxation at a reduced level.

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“…The Krebs solution had the following composition: sodium chloride (118 mM); potassium chloride (KCl; (4.7 mM); calcium chloride (2.5 mM); magnesium sulfate (1.2 mM); mono potassium phosphate (1.17 mM); sodium bicarbonate (20 mM); ethylenediaminetetraacetic acid (0.01 mM), and glucose. 12 The rings were maintained at 37 C and gassed with 95% oxygen and 5% carbon dioxide mixture (pH ¼ 7.4). The contractile response (isometric tension, in grams) was measured by a force transducer (model FT-03, Grass Technologies, Warwick, Rhode Island, USA) and coupled to a data acquisition system (AD Instruments, Dunedin, New Zealand).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Vasorelaxant effects of mercury on rat thoracic aorta

et al. 2013

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Mercury, a heavy metal, is widespread and persistent in the environment and has been elucidated as a possible risk factor in cardiovascular diseases. Mercury has been reported to selectively impair the nitric oxide (NO) pathway in the vascular endothelium as a consequence of oxidative stress. Conversely, mercury per se causes endothelium-dependent vasorelaxation at lower concentration via the NO pathway. Little is known about the effects of mercury per se on other endothelial mediators. To elucidate possible mechanisms involved in this action, isometric tension was measured in aortic rings precontracted with phenylephrine (10 µM) from Wistar rats. Responses to increasing concentrations of inorganic mercuric chloride (10−12–10−5 M) were obtained in the presence and absence of endothelium. Inorganic mercury produced a biphasic response in endothelium-intact aortic rings and produced only vasoconstriction in endothelium-denuded aortic rings. To study the possible underlying mechanisms for the biphasic response of mercury, increasing concentrations of mercuric chloride (10−12–10−5 M) were used before and after NG-nitro-l-arginine methyl ester (L-NAME (10−4 M)), glybenclamide (10−5 M), superoxide dismutase (10 U/ml) + catalase (100 U/ml), and nifedipine (10−4 M) treatment. Results suggest that mercury produces endothelium-dependent relaxation at low concentration mediated by endothelial-generated NO and endothelium-derived hyperpolarizing factor and endothelium-independent contraction resulting from the blockade of l-type Ca2+ channels by generation of free radicals.

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Altered alpha adrenergic vasoresponsiveness in a non‐cirrhotic portal hypertension model of E. coli injection

Abstract: Repeated injection of lipopolysaccharide into the gastrosplenic vein leads to the development of portal hypertension. This non-cirrhotic model of portal hypertension is characterized by generalized arterial hyporeactivity to vasoconstrictors akin to other models of portal hypertension.

Cited by 6 publications

References 43 publications

Modulation of Vasodilator Response via the Nitric Oxide Pathway after Acute Methyl Mercury Chloride Exposure in Rats

Modulation of Vasodilator Response via the Nitric Oxide Pathway after Acute Methyl Mercury Chloride Exposure in Rats

Persistence of EDHF pathway and impairment of the nitric oxide pathway after chronic mercury chloride exposure in rats: Mechanisms of endothelial dysfunction

Vasorelaxant effects of mercury on rat thoracic aorta

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