Study on the vascular reactivity and α<sub>1</sub>‐adrenoceptors of portal hypertensive rats

Liao, Jyh‐Fei; Yu, Pi-Chin; H, Lin; Lee, Fa-Yauh; Kuo, Jon Son; Yang, Meng

doi:10.1111/j.1476-5381.1994.tb14755.x

Cited by 47 publications

(26 citation statements)

References 33 publications

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“…Regarding this, the hypothesis of pronounced postjunctional ''smooth muscle desensitization'' has to be supplemented, for it seems that the pronounced depletion of pressure response to sustained SNS activity is at least partly attributable to an enhanced prejunctional depletion of NA release and deficient NPY release. This concurs with the fact that vascular hyporesponsiveness in cirrhosis is not due to changes in the affinity and/or number of postsynaptic a 1 -1 adrenoceptors [37]. Since NPY is a potent amplifier of the vasoconstrictive response to NA [13][14][15][16], it appears that not the absolute amount, but rather the proportion of transmitter/cotransmitter release is essential for vasoconstriction.…”

Section: Discussionsupporting

confidence: 67%

Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous neuropeptide Y

Dietrich¹,

Moleda²,

Kees

et al. 2013

Journal of Hepatology

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Section: Discussionsupporting

confidence: 67%

Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous neuropeptide Y

Dietrich¹,

Moleda²,

Kees

et al. 2013

Journal of Hepatology

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“…This hyporeactivity is not caused by ␣ 1 -adrenoceptor down-regulation 34,35 but by endothelial NO overproduction. 3,5,7,9,10,12,31,35,36 In this study, however, hyporeactivity to phenylephrine in superior mesenteric arteries during NO inhibition was caused by baseline EDHF-induced relaxation.…”

Section: Discussionmentioning

confidence: 86%

Evidence for an Endothelium-Derived Hyperpolarizing Factor in the Superior Mesenteric Artery From Rats With Cirrhosis

Barrière

Tazi

Rona³

et al. 2000

Hepatology

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In cirrhosis, in splanchnic arteries, endothelium-dependent relaxation may persist even if overactive nitric oxide synthase (NOS) and cyclooxygenase (COX) are inhibited. In normal arteries, a significant endothelium-dependent relaxation to acetylcholine persists after NOS/COX inhibition. This relaxation is caused by smooth muscle cell (SMC) membrane hyperpolarization, which is sensitive to a combination of the potassium channel blockers apamin and charybdotoxin, and is mediated by an endothelium-derived hyperpolarizing factor (EDHF). The aim of this study was to detect EDHF and evaluate its pathophysiologic role in isolated superior mesenteric arteries from cirrhotic rats. Arterial rings were obtained and exposed to N w -nitro-L-arginine (L-NNA, a NOS inhibitor) and indomethacin (a COX inhibitor). Acetylcholine-induced membrane potential responses and concentration-response curves to the relaxant of acetylcholine were obtained with and without apamin plus charybdotoxin. Acetylcholine-induced responses were measured in certain rings from endothelium-denuded arteries. Contractions caused by the ␣ 1 -adrenoceptor agonist phenylephrine were obtained in cirrhotic and normal rings with and without apamin and charybdotoxin. Significant acetylcholine-induced, endothelium-dependent, apamin-and charybdotoxin-sensitive, SMC membrane hyperpolarization and relaxation were found. An apamin-and charybdotoxinsensitive hyporesponsiveness to the contractile action of phenylephrine was found in cirrhotic rings. In conclusion, in cirrhotic rats, in the superior mesenteric artery exposed to NOS/COX-inhibitors, an EDHF exists that may replace NOS/COX products to induce endothelium-dependent arterial relaxation. (HEPATOLOGY 2000;32:935-941.)In portal hypertension, in splanchnic and systemic arteries, certain mechanisms induce endothelium-dependent smooth muscle cell (SMC) relaxation and hyporeactivity to vasoconstrictors by activating endothelial nitric oxide synthase (NOS) and cyclooxygenase (COX) to produce nitric oxide (NO) and prostacyclin (PGI 2 ). 1-12 However, it has been shown that, in portal hypertensive rats, NOS inhibition, alone or combined with COX inhibition, did not suppress arterial SMC relaxation and hyporeactivity to vasoconstrictors. 3,4,6,8 These findings show that a NOS/COX-inhibitor-insensitive SMC relaxation may be involved in arterial alterations associated with portal hypertension. It should be kept in mind that, in normal arteries, a significant endothelium-dependent arterial SMC relaxation (caused by shear stress or acetylcholine) persists even after NOS/COX inhibition. [13][14][15][16][17] This NOS/COX-inhibitor-insensitive relaxation is caused by SMC membrane hyperpolarization caused by endothelium-derived hyperpolarizing factors (EDHFs). 15,[17][18][19][20] In normal splanchnic arteries, a combination of the K ϩ channel blockers, apamin and charybdotoxin, 21 is known to inhibit EDHF-induced SMC hyperpolarization and relaxation. [22][23][24][25][26] In addition, a combination of barium (a K ϩ channel block...

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“…The observed vasoconstrictor dysfunction is systemic in nature in that it is not limited to the splanchnic vascular territory (13,18,19). This finding has been attributed to a postreceptor defect in vascular smooth muscle excitation contraction coupling (21,24). Additional evidence supports the contention that prolonged elevation in cyclic nucleotide-dependent vasodilators plays an important role in this defect inasmuch as vasoconstrictor effectiveness in portal hypertension can be restored by protein kinase A (PKA) inhibition (31).…”

mentioning

confidence: 78%

Effects of chronic portal hypertension on agonist-induced actin polymerization in small mesenteric arteries

Chen¹,

Pavlish²,

Zhang³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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. Effects of chronic portal hypertension on agonist-induced actin polymerization in small mesenteric arteries. Am J Physiol Heart Circ Physiol 290: H1915-H1921, 2006. First published December 9, 2005 doi:10.1152/ajpheart.00643.2005.-The ability of arterial smooth muscle to respond to vasoconstrictor stimuli is reduced in chronic portal hypertension (PHT). Additional evidence supports the existence of a postreceptor defect in vascular smooth muscle excitation contraction coupling. However, the nature of this defect is unclear. Recent studies have shown that vasoconstrictor stimuli induce actin polymerization in smooth muscle and that the associated increase in F-actin is necessary for force development. In the present study we have tested the hypothesis that impaired actin polymerization contributes to reduced vasoconstrictor function in small mesenteric arteries derived from rats with chronic prehepatic PHT. In vitro studies were conducted on small mesenteric artery vessel rings isolated from normal and PHT rats. Isometric tension responses to incremental concentrations of phenylephrine were significantly reduced in PHT arteries. The ability to polymerize actin in portal hypertensive mesenteric arteries stimulated by phenylephrine was attenuated compared with control. Inhibition of cAMP-dependent protein kinase (PKA) restored agonist-induced actin polymerization of arteries from PHT rats to normal levels. Depolymerization of actin in arteries from normal rats reduced maximal contractile force but not myosin phosphorylation, suggesting a key role for the dynamic regulation of actin polymerization in the maintenance of vascular smooth muscle contraction. We conclude that reductions in agonistinduced maximal force development of PHT vascular smooth muscle is due, in part, to impaired actin polymerization, and prolonged PKA activation may underlie these changes. vascular smooth muscle; protein kinase A; myosin; phenylephrine; isometric tension ONE OF THE MOST INTRIGUING vascular consequences of chronic portal hypertension is the decreased ability of blood vessels to respond to vasoconstrictor stimuli (2, 3). The observed vasoconstrictor dysfunction is systemic in nature in that it is not limited to the splanchnic vascular territory (13,18,19). This finding has been attributed to a postreceptor defect in vascular smooth muscle excitation contraction coupling (21, 24). Additional evidence supports the contention that prolonged elevation in cyclic nucleotide-dependent vasodilators plays an important role in this defect inasmuch as vasoconstrictor effectiveness in portal hypertension can be restored by protein kinase A (PKA) inhibition (31). However, the cellular mechanism whereby cyclic nucleotide-dependent pathways impair vasoconstriction in chronic portal hypertension is still unclear.Most previous investigations suggested that cyclic nucleotide-dependent relaxation occurs through inhibition or reversal of the Ca 2ϩ -dependent phosphorylation of the regulatory myosin light chain (MLC 20 ). However, prolonged activat...

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Study on the vascular reactivity and α₁‐adrenoceptors of portal hypertensive rats

Cited by 47 publications

References 33 publications

Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous neuropeptide Y

Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous neuropeptide Y

Evidence for an Endothelium-Derived Hyperpolarizing Factor in the Superior Mesenteric Artery From Rats With Cirrhosis

Effects of chronic portal hypertension on agonist-induced actin polymerization in small mesenteric arteries

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Study on the vascular reactivity and α1‐adrenoceptors of portal hypertensive rats

Cited by 47 publications

References 33 publications

Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous neuropeptide Y

Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous neuropeptide Y

Evidence for an Endothelium-Derived Hyperpolarizing Factor in the Superior Mesenteric Artery From Rats With Cirrhosis

Effects of chronic portal hypertension on agonist-induced actin polymerization in small mesenteric arteries

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Study on the vascular reactivity and α₁‐adrenoceptors of portal hypertensive rats