Endothelium-mediated and Nω-nitro-l-arginine methyl ester-sensitive responses to cromakalim and diazoxide in the rat mesenteric bed

Feleder, Ethel; Adler‐Graschinsky, Edda

doi:10.1016/s0014-2999(96)00843-6

Cited by 16 publications

(12 citation statements)

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“…Interestingly, the response to diazoxide was attenuated in endothelium-denuded vessels, suggesting that a small part of the response may be endothelium dependent. This was reported previously for low concentrations of diazoxide (30 M) and was linked to NO production; higher concentrations of diazoxide were not affected by endothelium removal or by treatment with a NOS inhibitor (11). Others have reported that removal of the endothelium enhances the vasodilating effects of potassium channel openers like pinacidil and levcromakalim (19).…”

Section: Discussionsupporting

confidence: 73%

Effect of phosphodiesterase 5 inhibitor on alteration in vascular smooth muscle sensitivity and renal function in rats with liver cirrhosis

Tahseldar-Roumieh¹,

Ghali-Ghoul²,

Lugnier³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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. Effect of phosphodiesterase 5 inhibitor on alteration in vascular smooth muscle sensitivity and renal function in rats with liver cirrhosis. Am J Physiol Heart Circ Physiol 290: H481-H488, 2006; doi:10.1152/ajpheart.00507.2005.-Previous studies suggested that increased activity of phosphodiesterase (PDE)5 in the kidneys of cirrhotic rats contributes to sodium retention. This study examined the role of PDE5 in the changes in vascular reactivity, hemodynamics, and sodium excretion in rats with liver cirrhosis. Four weeks after bile duct ligation (BDL) or sham operation (SO), in vitro reactivity of aortic rings to various agents and in vivo effects of a PDE5-selective inhibitor [1,3-dimethyl-6-(2-propoxy-5-methanesulfonylamidophenyl)pyrazolo-[3,4d]-pyrimidin-4-(5H)-one, DMPPO] were studied. The vasodilator responses to nitroglycerin and S-nitroso-N-acetyl-penicillamine (SNAP) in phenylephrine-precontracted rings without endothelium were attenuated in BDL compared with SO rats. Pretreatment with DMPPO (0.1 M) enhanced these responses and eliminated the differences between the two groups. Vasodilation to DMPPO itself was also less in BDL rats. The responses to phenylephrine were attenuated in endothelium-rich aorta from BDL relative to SO rats, but they were similar in endotheliumdenuded aorta and remained similar despite preincubation with SNAP (0.1 M) alone or with SNAP and DMPPO. In vivo, BDL rats were vasodilated relative to SO rats; DMPPO (5 mg/kg iv) decreased arterial pressure and vascular resistance in both groups equally and caused significant increase in sodium excretion in BDL rats only. In conclusion, the results are in accordance with a possible increase in PDE5 activity in aorta and kidney of cirrhotic rats that results in reduced responses to NO donors and contributes to the increase in sodium retention. PDE5 inhibitors may ameliorate sodium retention in cirrhosis but may worsen vasodilation. Examining the effect of PDE5 inhibitors after chronic administration will be more revealing.hemodynamics; nitric oxide; vasodilation; sodium retention; guanosine 3Ј,5Ј-cyclic monophosphate CIRRHOSIS OF THE LIVER is associated with development of sodium retention by the kidney, renal vasoconstriction, and peripheral vasodilation especially in the splanchnic vasculature, leading to a hyperdynamic circulation (26). The pathogenesis of these findings has been the subject of numerous studies. Much evidence has been provided to support a role of NO in the genesis of splanchnic vasodilation (32). In addition, several studies have suggested that NO overproduction accounts for the decreased sensitivity of the mesenteric vasculature to vasoconstrictors (2, 3). However, some studies failed to support a role for NO in cirrhosis-induced vasodilation (12, 27), and it was recently shown that mice with a targeted deletion of endothelial nitric oxide synthase (eNOS) still developed the hyperdynamic circulation and peripheral vasodilation characteristic of portal hypertension (13), which suggested that other factors contributed ...

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Section: Discussionsupporting

confidence: 73%

Effect of phosphodiesterase 5 inhibitor on alteration in vascular smooth muscle sensitivity and renal function in rats with liver cirrhosis

Tahseldar-Roumieh¹,

Ghali-Ghoul²,

Lugnier³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Many VSM constrictors usually induced per se tonic NO release in vessels, among them, phenylephrine and high potassium were chosen to evaluate NO releasing in the endothelial cell (Dora et al, 1997). In the present study, MCPT-induced relaxation was blocked by glibenclamide in both endothelium-intact and -denuded aorta, therefore, we cannot exclude the possibility of vasorelaxant responses of MCPT is modulated by the activation of endothelial K ATP channels (Feleder and Adler-Graschinsy, 1997). We suggested that MCPT-induced vasorelaxation might be partly via the opening of K + channels on endothelial cells and vascular smooth muscle cells.…”

Section: Discussionmentioning

confidence: 76%

“…The action of NO as a vasodilator is mediated by the activation of vascular smooth muscle sGC, a signal transduction enzyme that forms the second messenger molecular cGMP (Arnold et al, 1977;Lowenstein et al, 1994). It is suggested that activation of endothelium K ATP channels may also release endothelium-derived nitric oxide (Feleder and Adler-Graschinsy, 1997) or endothelium-derived hyperpolarizing factor (White and Hiley, 1997). Nitric oxide donors have been shown to activate K ATP channels via a cGMP-dependent mechanism, presumably involving activation of cGMP-dependent protein kinase in rat aortic smooth muscle cells (Kubo et al, 1993) and rabbit mesenteric artery (Murphy and Brayden, 1995), and by a cGMP-independent mechanism in rat mesenteric artery (Weidelt et al, 1997).…”

mentioning

confidence: 99%

Endothelium-dependent and -independent vasorelaxation by a theophylline derivative MCPT: Roles of cyclic nucleotides, potassium channel opening and phosphodiesterase inhibition

Tsou

Lin

et al. 2005

Life Sciences

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“…Although diazoxide can cause vasodilation in the absence of an intact endothelium (Antoine, et al, 1992), several reports indicate the endothelium to be another diazoxide target (Feleder & Adler-Graschinsky, 1997). In humans, plethysmography recordings of forearm blood flow demonstrated that endothelial function is impaired by ischemia (induced by blood pressure cuff inflation), which is prevented by IPC or diazoxide pre-administration (800 µg/min for 20 min) (Broadhead, et al, 2004).…”

Section: Are Endothelial Katp Channels Involved?mentioning

confidence: 99%

Multiplicity of effectors of the cardioprotective agent, diazoxide

Coetzee

2013

Pharmacology & Therapeutics

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Diazoxide has been identified over the past 50 years to have a number of physiological effects, including lowering the blood pressure and rectifying hypoglycemia. Today it is used clinically to treat these conditions. More recently, another important mode of action emerged: diazoxide has powerful protective properties against cardiac ischemia. The heart has intrinsic protective mechanisms against ischemia injury; one of which is ischemic preconditioning. Diazoxide mimics ischemic preconditioning. The purpose of this treatise is to review the literature in an attempt to identify the many effectors of diazoxide and discuss how they may contribute diazoxide’s cardioprotective properties. Particular emphasis is placed on the concentration ranges in which diazoxide affects its different targets and how this compares with the concentrations commonly used to study cardioprotection. It is concluded that diazoxide may have several potential effectors that may potentially contribute to cardioprotection, including KATP channels in the pancreas, smooth muscle, endothelium, neurons and the mitochondrial inner membrane. Diazoxide may also affect other ion channels and ATPases and may directly regulate mitochondrial energetics. It is possible that the success of diazoxide lies in this promiscuity and that the compound acts to rebalance multiple physiological processes during cardiac ischemia.

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Endothelium-mediated and Nω-nitro-l-arginine methyl ester-sensitive responses to cromakalim and diazoxide in the rat mesenteric bed

Cited by 16 publications

References 50 publications

Effect of phosphodiesterase 5 inhibitor on alteration in vascular smooth muscle sensitivity and renal function in rats with liver cirrhosis

Effect of phosphodiesterase 5 inhibitor on alteration in vascular smooth muscle sensitivity and renal function in rats with liver cirrhosis

Endothelium-dependent and -independent vasorelaxation by a theophylline derivative MCPT: Roles of cyclic nucleotides, potassium channel opening and phosphodiesterase inhibition

Multiplicity of effectors of the cardioprotective agent, diazoxide

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