Cellular stress inhibits vascular smooth muscle relaxation

Knoepp, Louis F.; Beall, Arthur C.; Woodrum, David A.; Mondy, J. Sheppard; Shaver, Ellen G.; Dickinson, Mary; Brophy, Colleen M.

doi:10.1016/s0741-5214(00)90164-2

Cited by 28 publications

(20 citation statements)

References 40 publications

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“…Vascular tissue cellular stress induces reduced vasorelaxation reported to be associated with a concomitant rise in HSP27 and fall in HSP20 phosphorylation (9). In the myocardium, a positive correlation between tissue cGMP content and the magnitude of HSP27 phosphorylation has been reported (11).…”

Section: Discussionmentioning

confidence: 99%

Newborn rat response to single vs. combined cGMP-dependent pulmonary vasodilators

Enomoto

Jain

Pan

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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. Newborn rat response to single versus combined cGMP-dependent pulmonary vasodilators. Am J Physiol Lung Cell Mol Physiol 306: L207-L215, 2014. First published November 15, 2013 doi:10.1152/ajplung.00164.2013.-Inhaled nitric oxide (NO) and other cGMP-or cAMP-dependent pulmonary vasodilators are often used in combination for the treatment of the persistent pulmonary hypertension of the newborn syndrome. There is in vitro evidence to indicate that NO downregulate the pulmonary vascular response to cGMP-dependent agonists raising concern as to whether a synergistic effect is observed when employing a combined strategy in newborns. Hypothesizing that a synergistic effect is absent, we evaluated newborn and juvenile rat pulmonary arteries to determine the individual and combined vasodilatory effect of cGMP-and cAMP-dependent agonists. In precontracted near-resistance pulmonary arteries, the addition of sildenafil reduced vasorelaxation response to NO donor S-nitroso-N-acetyl penicillamine (SNAP). A similar decrease in SNAP-induced vasodilation was observed in arteries pretreated with BAY 41-2272 (10 Ϫ9 M), a soluble guanylate cyclase stimulator cGMP, and its downstream protein kinase activator. cGMP also reduced the vasorelaxant response to the cAMPdependent forskolin. Inhibition of endogenous vascular NO generation enhanced SNAP-induced relaxation. The present data suggest that the mechanism involved in the cGMP desensitization to other relaxant agonists involves downregulation of the small heat shock protein HSP20 and is evident in rat pulmonary and systemic vascular smooth muscle cells. In newborn rats with chronic hypoxia-induced pulmonary hypertension, the combination of sildenafil and inhaled NO resulted in a lesser reduction in pulmonary vascular resistance compared with their individual effect. These data suggest that clinical exposure to one cGMP-dependent pulmonary vasodilator may affect the response to other cGMP-or cAMP-mediated agonists.sildenafil; nitric oxide; pulmonary hypertension; adenosine 3=,5=-cyclic monophosphate; guanosine 3=,5=-cyclic monophosphate THE SUCCESSFUL TRANSITION from fetal to postnatal life depends on a rapid decrease in pulmonary vascular resistance (PVR) at birth. The factors accounting for this dramatic reduction in PVR are incompletely understood, but nitric oxide (NO) is known to play an important role. The maintenance or recurrence of a high PVR postnatally characterizes the persistent pulmonary hypertension of the newborn syndrome (PPHN), a life-threatening condition requiring early and aggressive therapeutic interventions to improve and maintain adequate blood oxygenation (21).Inhaled NO is the standard of care to therapeutically promote pulmonary vasodilation in infants with PPHN, and significant clinical improvement is observed in many infants subjected to this therapy (2, 4). Yet, when response to inhaled NO is absent or partial, the clinical use of alternative agents with pulmonary vasodilatory properties may be contemplated (29).NO is endogenously generated by nitric...

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Section: Discussionmentioning

confidence: 99%

Newborn rat response to single vs. combined cGMP-dependent pulmonary vasodilators

Enomoto

Jain

Pan

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…For instance, recent data suggest that the activation of the PI3-kinase/Akt pathway in unstimulated smooth muscle may modulate vascular smooth muscle tone through inhibition of the cAMP/heat shock-related protein 20 (HSP20) pathways (23,24). Although another heat shock-related protein, HSP27, has been shown to be involved in vascular smooth muscle contraction, whether HSP20, a substrate for protein kinases A and G, mediates vascular relaxation, possibly via a direct interaction of large aggregates of HSP20 with the contractile elements, independently of Ca 2ϩ /myosin light chain regulatory pathway remains to be determined (4,7,22,46). Numerous agonists, including PGF 2␣ , have been shown to activate PI3-kinase pathway (5,34,39,44).…”

Section: Discussionmentioning

confidence: 99%

Involvement of p38-mitogen-activated protein kinase in adenosine receptor-mediated relaxation of coronary artery

Teng¹,

Qin²,

Ansari³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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Teng, Bunyen, Weixi Qin, Habib R. Ansari, and S. Jamal Mustafa. Involvement of p38-mitogen-activated protein kinase in adenosine receptor-mediated relaxation of coronary artery. Am J Physiol Heart Circ Physiol 288: H2574 -H2580, 2005. First published January 14, 2005 doi:10.1152/ajpheart.00912.2004.-The purpose of this study was to explore the involvement of adenosine receptor(s) in porcine coronary artery (PCA) relaxation and to define the role of MAPK signaling pathways. Isometric tensions were recorded in denuded PCA rings. 5Ј-(N-ethylcarboxamido)adenosine (NECA), a nonselective adenosine receptor agonist, induced a concentrationdependent relaxation (EC 50 ϭ 16.8 nM) of PGF2␣ (10 M)-preconstricted arterial rings. NECA-induced relaxation was completely blocked by 0.1 M SCH-58261 (A 2A antagonist) at lower doses (1-40 nM) but not at higher doses (80 -1,000 nM). MRS-1706 (1 M, A 2B antagonist) was able to shift the NECA concentration-response curve to the right. CGS-21680 (selective A2A agonist) induced responses similarly to NECA, whereas N 6 -cyclopentyladenosine (A1 agonist) and Cl-IB-MECA (A3 agonist) did not. Furthermore, the effect of NECA was attenuated by the addition of SB-203580 (10 M, p38 MAPK inhibitor) but not by PD-98059 (10 M, MEK inhibitor). Interestingly, SB-203580 had no effect on CGS-21680-induced relaxation. Western blot analysis demonstrated that PGF 2␣ and adenosine agonists stimulated p38 MAPK at a concentration of 40 nM in PCA smooth muscle cells. MRS-1706 (1 M) significantly reduced NECAinduced p38 MAPK phosphorylation. Addition of NECA and SB-203580 alone or in combination inhibited PGF 2␣-induced p38 MAPK. Western blot data were further confirmed by p38 MAPK activity measurement using activating transcription factor-2 assay. Our results suggest that the adenosine receptor subtype involved in causing relaxation of porcine coronary smooth muscle is mainly A 2A subtype, although A2B also may play a role, possibly through p38 MAPK pathway. adenosine receptors; vascular smooth muscle; p42/44; c-Jun NH2-terminal kinase; prostaglandin F2␣ ADENOSINE IS KNOWN TO CAUSE dilation of coronary artery. Four adenosine receptor subtypes, A 1 , A 2A , A 2B , and A 3 , have been identified and cloned (14). It has been suggested that both A 2A and A 2B adenosine receptors mediate hyperpolarization and nitric oxide (NO) release from coronary artery endothelium (2, 30, 47). The adenosine receptor subtypes responsible for endothelium-independent vasodilation in coronary artery smooth muscle are still not fully understood; however, both A 2A and A 2B adenosine receptors have been implicated (28,40,41).Upon activation, both A 2A and A 2B receptors, which are coupled to G s protein and subsequently activate adenylyl cyclase, cause an activation of various second messenger systems, including mitogen-activated protein kinases (MAPKs). There are three well-characterized MAPKs: extracellular signal-regulated kinases (ERKs, or p42/44), p38, and c-Jun NH 2 -terminal kinase (JNK). These MAPKs have been linked to isch...

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“…One mechanism for this appears to be increased sodium content of the blood vessels [2]; however, other factors such as cellular stress and hypoxia can inhibit vascular relaxation in reactions involving heat shock proteins [17].…”

Section: Blood Flow Measurementsmentioning

confidence: 99%

Cutaneous vascular reactivity is reduced in aging and in heart failure: association with inflammation

Andersson

Edvinsson

2003

Clinical Science

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In the present study, we have investigated whether changes in vascular reactivity in congestive heart failure (CHF) patients can be detected in the cutaneous microvessels and whether these changes are due to endothelial dysfunction, are affected by increasing age and related to an ongoing inflammation. The responses to local warming and iontophoretically administered endothelium-dependent and -independent vasodilators were investigated in healthy young adults, healthy elderly adults and elderly adults with CHF. The results were correlated with plasma concentrations of vascular risk factors and markers for endothelial dysfunction and inflammation. The vasorelaxant responses were reduced in the elderly groups and were attenuated further in the CHF group. This group also had increases in levels of several markers associated with inflammation, higher blood glucose and homocysteine levels, a lower low-density lipoprotein-cholesterol and a rise in the concentration of von Willebrand factor, indicating a prothrombotic endothelial function. The severity of the heart failure, measured as the plasma level of brain natriuretic peptide, correlated with the intensity of inflammation and to the changes in vascular risk factors and endothelial function. It is concluded that the reactivity of the cutaneous microvessels is reduced with age, and the presence of CHF causes a further impairment. There is endothelial dysfunction in CHF, but it is uncertain to what extent this contributes to the reduced vasodilatory capacity. The inflammatory response appears central for many of the manifestations of the CHF syndrome.

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Cellular stress inhibits vascular smooth muscle relaxation

Abstract: Cellular stress, which leads to increases in the phosphorylation of HSP27, inhibits cyclic nucleotide-dependent vascular relaxation and cyclic nucleotide-dependent increases in the phosphorylation of HSP20.

Cited by 28 publications

References 40 publications

Newborn rat response to single vs. combined cGMP-dependent pulmonary vasodilators

Newborn rat response to single vs. combined cGMP-dependent pulmonary vasodilators

Involvement of p38-mitogen-activated protein kinase in adenosine receptor-mediated relaxation of coronary artery

Cutaneous vascular reactivity is reduced in aging and in heart failure: association with inflammation

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