Involvement of calcium/calmodulin-dependent protein kinase II to endotoxin-induced vascular hyporeactivity in rat superior mesenteric artery

Özveren, Elif; Korkmaz, Belma; Buharalioğlu, C. Kemal; Tunçtan, Bahar

doi:10.1016/j.phrs.2006.05.001

Cited by 8 publications

(6 citation statements)

References 72 publications

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“…Similarly, melatonin may directly affect the ion channels responsible for regulating bladder contraction or changing membrane potentials that affect other ion channels [12]. KN-93 selectively inhibits CaMKII activity by binding directly and selectively to the calmodulin binding site of CaMKII and preventing the association of calmodulin and CaMKII [22]. Our study found that KN-93 enhanced the melatonin-induced relaxation response in the bladder strips, indicating that melatonin may act on the calmodulin/CaMKII system.…”

Section: Discussionmentioning

confidence: 74%

A Novel Pathway Underlying the Inhibitory Effects of Melatonin on Isolated Rat Urinary Bladder Contraction

Han

Chang

Myung

et al. 2012

Korean J Physiol Pharmacol

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The aim of the present study was to elucidate the direct effects of melatonin on bladder activity and to determine the mechanisms responsible for the detrusor activity of melatonin in the isolated rat bladder. We evaluated the effects of melatonin on the contractions induced by phenylephrine (PE), acetylcholine (ACh), bethanechol (BCh), KCl, and electrical field stimulation (EFS) in 20 detrusor smooth muscle samples from Sprague-Dawley rats. To determine the mechanisms underlying the inhibitory responses to melatonin, melatonin-pretreated muscle strips were exposed to a calcium channel antagonist (verapamil), three potassium channel blockers [tetraethyl ammonium (TEA), 4-aminopyridine (4-AP), and glibenclamide], a direct voltage-dependent calcium channel opener (Bay K 8644), and a specific calcium/calmodulin-dependent kinase II (CaMKII) inhibitor (KN-93). Melatonin pretreatment (10-8~10-6 M) decreased the contractile responses induced by PE (10-9~10-4 M) and Ach (10-9~10-4 M) in a dose-dependent manner. Melatonin (10-7 M) also blocked contraction induced by high KCl ([KCl]ECF; 35 mM, 70 mM, 105 mM, and 140 mM) and EFS. Melatonin (10-7 M) potentiated the relaxation response of the strips by verapamil, but other potassium channel blockers did not change melatonin activity. Melatonin pretreatment significantly decreased contractile responses induced by Bay K 8644 (10-11~10-7 M). KN-93 enhanced melatonin-induced relaxation. The present results suggest that melatonin can inhibit bladder smooth muscle contraction through a voltage-dependent, calcium-antagonistic mechanism and through the inhibition of the calmodulin/CaMKII system.

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Section: Discussionmentioning

confidence: 74%

A Novel Pathway Underlying the Inhibitory Effects of Melatonin on Isolated Rat Urinary Bladder Contraction

Han

Chang

Myung

et al. 2012

Korean J Physiol Pharmacol

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“…These results show that CaMKII activity is required for upregulation of iNOS and caspase-3 in the diabetic retinas. CaMKII is known to be a potent upstream regulator of iNOS (Jones et al, 2007;Ozveren et al, 2006). In addition, overexpression of CaMKII or iNOS can trigger caspase-3-dependent cell death in damaged retinas (Coo-per et al, 2008;Goebel, 2009;She et al, 2007) and both contribute to diabetic pathology (Ko et al, 2008;Li and Mahato, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Several reports have suggested that CaMKII activation plays a critical role in iNOS-induced vascular lesions (Jones et al, 2007;Ozveren et al, 2006;Zhang et al, 2003), however there have been no reports on the correlation between CaMKII activation and iNOS induction in diabetes and/or in the retina. In the present study, we investigated whether CaMKII affects iNOS-related pericyte death in diabetic mouse retinas.…”

Section: Introductionmentioning

confidence: 99%

CaMKII Regulates Pericyte Loss in the Retina of Early Diabetic Mouse

Kim

Park

et al. 2011

Molecules and Cells

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Inducible nitric oxide synthase (iNOS) is an essential mediator in diabetic vascular lesions and known to be regulated by activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). The aim of this study was to investigate whether CaMKII affects iNOS-mediated pericyte death in the retina of diabetic mice with early stage disease. Total- and phospho-CaMKII, iNOS, and active caspase-3 protein levels were assessed by Western blotting, and CaMKII activity was measured by kinase assay. iNOS-related pericyte death was assessed by double immunofluorescent staining for iNOS and α-smooth muscle actin, followed by the TUNEL assay. Autocamtide-2-related inhibitory peptide (AIP), a specific inhibitor of CaMKII, was injected into the right vitreous 2 days before sacrifice of mice, to examine the effect of CaMKII inactivation in diabetic retinas. The levels of total- and phospho-CaMKII, iNOS, and active caspase-3 protein, and CaMKII activity were significantly increased in the diabetic retinas compared with those of control retinas. Furthermore, TUNEL-positive signals colocalized with iNOS-immunoreactive pericytes in the same retinas. However, inactivation of CaMKII by AIP treatment inhibited all these changes, which was accompanied by less pericyte loss. Our results demonstrate that CaMKII contributes to iNOS-related death of pericytes in the diabetic retina and that inactivation of this enzyme may be a potential treatment for retinal vascular lesion.

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“…At the end of the experiment, the rats were killed, and the thoracic aortas and superior mesenteric arteries were isolated as previously described (11, 12). The vessels were cleared of adventitial tissue and cut into rings of 2 to 3 mm in length.…”

Section: Methodsmentioning

confidence: 99%

A 20-Hydroxyeicosatetraenoic Acid Agonist, N-[20-Hydroxyeicosa-5(z),14(z)-Dienoyl]glycine, Opposes the Fall in Blood Pressure and Vascular Reactivity in Endotoxin-Treated Rats

Tunçtan

Korkmaz

Buharalioğlu

et al. 2008

Shock

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Endotoxic shock is a systemic inflammatory response that is associated with an increase in nitric oxide production and a decrease in the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), which may contribute to the fall in blood pressure and vascular reactivity. The present study examined the effects of a synthetic analogue of 20-HETE, N-[20-hydroxyeicosa-5(Z),14(Z)-dienoyl]glycine (5,14-HEDGE), on the fall in blood pressure and vascular responsiveness to vasoscontrictors and acetylcholine in rats treated with endotoxin. The MAP fell by 31 mmHg, and the heart rate rose by 90 beats/min in male Wistar rats treated with endotoxin (10 mg/kg, intraperitoneally). The fall in MAP was associated with a decrease in the vasoconstrictor response to norepinephrine in isolated aorta and superior mesenteric artery and increased levels of nitrite in the serum, kidney, heart, and vascular tissues. The effects of endotoxin were prevented by 5,14-HEDGE (30 mg/kg, s.c.) given 1 h after injection of endotoxin. Furthermore, a competitive antagonist of vasoconstrictor effects of 20-HETE, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (30 mg/kg, s.c.), prevented the beneficial effects of 5,14-HEDGE on MAP and vascular tone in rats treated with endotoxin. These data are consistent with the view that a fall in the production of 20-HETE contributes to the fall in MAP and vascular reactivity in rats treated with endotoxin, and that 5,14-HEDGE has a beneficial effect.

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Involvement of calcium/calmodulin-dependent protein kinase II to endotoxin-induced vascular hyporeactivity in rat superior mesenteric artery

Cited by 8 publications

References 72 publications

A Novel Pathway Underlying the Inhibitory Effects of Melatonin on Isolated Rat Urinary Bladder Contraction

A Novel Pathway Underlying the Inhibitory Effects of Melatonin on Isolated Rat Urinary Bladder Contraction

CaMKII Regulates Pericyte Loss in the Retina of Early Diabetic Mouse

A 20-Hydroxyeicosatetraenoic Acid Agonist, N-[20-Hydroxyeicosa-5(z),14(z)-Dienoyl]glycine, Opposes the Fall in Blood Pressure and Vascular Reactivity in Endotoxin-Treated Rats

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