Direct effects of Rho-kinase inhibitor on pial microvessels in rabbits

Kotoda, Masakazu; Ishiyama, Tadahiko; Shintani, Noriyuki; Matsukawa, Takashi

doi:10.1007/s00540-014-1903-x

Cited by 3 publications

(7 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Without Y-27632, pial arterioles were constricted at the ischemia, and were temporarily dilated and then were significantly constricted at the reperfusion period. These results concur with our previous studies [6, 7]. When Y-27632 was applied only before the global cerebral ischemia, pial arterioles were not constricted at the ischemia, and were temporarily dilated and then were constricted but not significantly at the reperfusion period.…”

Section: Discussionsupporting

confidence: 93%

“…Y-27632 is reported to induce concentration-dependent reduction of myogenic tone in the rabbit facial vein [17]. However, we did not observe similar dilation of pial venules that is consistent with our previous experience [6]. …”

Section: Discussionsupporting

confidence: 91%

“…Myosin light chain is therefore phosphorylated persistently and smooth muscle constricts. We previously reported that Y-27632, a Rho-kinase inhibitor, dilates cerebral pial arterioles [6]. As would thus be expected, topical application of Y-27632 at 10 −6 mol/L dilated both large and small pial arterioles.…”

Section: Discussionsupporting

confidence: 55%

“…In the Post group, Y-27632 at 10 −6 mol∙L −1 was infused from 10 min after the global brain ischemia started until 120 min after unclamping. In our previous study, Y-27632 at 10 −6 mol∙L −1 produced substantial cerebral pial arteriolar dilation [6]. On the basis of this dose-ranging study, we thus selected 10 −6 mol∙L −1 as the concentration of Y-27632 for the current study.…”

Section: Methodsmentioning

confidence: 99%

“…Fasudil is a clinically available Rho-kinase inhibiter that reportedly increases cerebral blood flow [4]. Y-27632, another Rho-kinase inhibiter, dilates normal basilar arterioles [5] and cerebral pial arterioles [6]. …”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The effects of Y-27632 on pial microvessels during global brain ischemia and reperfusion in rabbits

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundGlobal brain ischemia-reperfusion during propofol anesthesia provokes persistent cerebral pial constriction. Constriction is likely mediated by Rho-kinase. Cerebral vasoconstriction possibly exacerbates ischemic brain injury. Because Y-27632 is a potent Rho-kinase inhibitor, it should be necessary to evaluate its effects on cerebral pial vessels during ischemia—reperfusion period. We therefore tested the hypotheses that Y-27632 dilates cerebral pial arterioles after the ischemia-reperfusion injury, and evaluated the time-course of cerebral pial arteriolar status after the ischemia-reperfusion.MethodsJapanese white rabbits were anesthetized with propofol, and a closed cranial window inserted over the left hemisphere. Global brain ischemia was produced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. Rabbits were assigned to cranial window perfusion with: (1) artificial cerebrospinal fluid (Control group, n = 7); (2) topical infusion of Y-27632 10−6 mol · L−1 for 30 min before the initiation of global brain ischemia (Pre group, n = 7); (3) topical infusion of Y-27632 10−6 mol · L−1 starting 30 min before ischemia and continuing throughout the study period (Continuous group, n = 7); and, (4) topical infusion of Y-27632 10−6 mol · L−1 starting 10 min after the ischemia and continuing until the end of the study (Post group, n = 7). Cerebral pial arterial and venule diameters were recorded 30 min before ischemia, just before arterial clamping, 10 min after clamping, and 5, 10, 20, 40, 60, 80, 100, and 120 min after unclamping.ResultsMean arterial blood pressure and blood glucose concentration increased significantly after global brain ischemia except in the Continuous group. In the Pre and Continuous groups, topical application of Y-27632 produced dilation of large (mean 18–19%) and small (mean; 25–29%) pial arteries, without apparent effect on venules. Compared with the Control and Pre groups, arterioles were significantly dilated during the reperfusion period in the Continuous and Post groups (mean at 120 min: 5–8% in large arterioles and 11–12% in small arterioles).ConclusionsY-27632 dilated cerebral pial arterioles during reperfusion. Y-27632 may enhance recovery from ischemia by preventing arteriolar vasoconstriction during reperfusion.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 55%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The effects of Y-27632 on pial microvessels during global brain ischemia and reperfusion in rabbits

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

Influence of pneumoperitoneum and head-down maneuver on the cerebral microvasculature in rabbits

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background With recent advances in robot-assisted techniques, an increasing number of surgeries are being performed with pneumoperitoneum and head-down maneuver (HDM) that may affect the cerebral microcirculation. For the first time, this study investigated the direct influence of pneumoperitoneum and HDM on the cerebral microvasculature in rabbits. Methods Adult male rabbits were randomly allocated to the following groups (n = 7 each): control, pneumoperitoneum alone (P), and pneumoperitoneum with HDM (P + HDM) for 120 min. A closed cranial window was installed above the parietal bone to visualize the pial microvasculature. Pial arteriolar diameter and hemodynamic and blood gas parameters were measured during the 140-min observation period. Brain edema was assessed by evaluation of the brain water content at the end of the experiment. Results Rabbits in the P and P + HDM groups exhibited a similar degree of immediate pial arteriolar dilation following the initiation of both P and P + HDM (P: 1.11 ± 0.03, p = 0.0044 and P + HDM: 1.07 ± 0.02, p = 0.0004, relative changes from the baseline value by defining the baseline as one). In the P + HDM group, pial arteriole diameter returned to the baseline level following the discontinuation of pneumoperitoneum and HDM (1.05 ± 0.03, p = 0.0906, vs. baseline). In contrast, the pial arterioles remained dilated as compared to the baseline level in the P group after discontinuation of pneumoperitoneum. There were no changes in pial arteriole diameter in the animals in the control group. Heart rate, blood gas parameters, and brain water content were not significantly different between the groups. Conclusion The pial arterioles dilated immediately after pneumoperitoneum with or without HDM. The pial arterioles remained dilated 20 min after discontinuation of pneumoperitoneum alone but constricted upon discontinuation of pneumoperitoneum plus HDM. Pneumoperitoneum and HDM for 2 h did not cause brain edema.

show abstract

Effects of β1-adrenergic receptor blockade on the cerebral microcirculation in the normal state and during global brain ischemia/reperfusion injury in rabbits

Asano

Hishiyama

Ishiyama

et al. 2020

BMC Pharmacol Toxicol

Self Cite

View full text Add to dashboard Cite

Background: Although recent studies using experimental models of ischemic brain injury indicate that systemically-administered β 1 -blockers have potential protective effects on the cerebrovascular system, the precise mechanisms remain unclear. In addition to their cardiovascular effects, water-soluble β 1 -blockers can pass the blood-brain barrier and may exert their vascular action on cerebral microvessels. The aim of this study was to investigate the direct effects of β 1 -blockade on the cerebral microvasculature both in the normal state and ischemia/reperfusion state using the cranial window method. Methods: The closed cranial window method was used to visualize the cerebral microcirculation and changes in the pial arteriole diameter in adult male rabbits. In the first experiment, various concentrations of the selective β 1blocker landiolol were administered into the cranial window to evaluate the dose-response. In the second experiment, the effect of β 1 -blockade on the brain during ischemic/reperfusion injury was investigated. Global brain ischemia/reperfusion was induced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. Either landiolol or artificial cerebrospinal fluid was infused 5 min after initiation of ischemia through 120 min after reperfusion. Pial arteriole diameter and hemodynamic and physiological parameters were recorded before ischemia, during ischemia, and 5, 10, 20, 40, 60, 80, 100, and 120 min after reperfusion. Results: In the first experiment, topical administration of landiolol at higher concentrations produced slight pial arteriole dilation (10 − 8 mol/L: 4.3 ± 3.4%, 10 − 6 mol/L: 8.0 ± 5.8%, 10 − 4 mol/L: 7.3 ± 4.0%). In the second experiment, the topical administration of landiolol significantly dilated the pial arteriole diameters during ischemia/reperfusion injury (ischemia: 30.6 ± 38.6%, 5 min: 47.3 ± 42.2%, 10 min: 47.8 ± 34.2%, 20 min: 38.0 ± 39.0%). There were no statistical differences in hemodynamic and physiological parameters between the landiolol and control groups. Conclusions: The blockade of β 1 -adrenergic receptors induced significant vasodilation of pial arterioles during ischemia/reperfusion injury. By contrast, only a slight dilation of the arterioles was observed in the normal state, indicating that ischemic cerebral microvessels are more susceptible to the vasodilatory effect induced by selective blockade of β 1 -adrenergic receptors than normal microvessels.

show abstract

Direct effects of Rho-kinase inhibitor on pial microvessels in rabbits

Abstract: We evaluated the direct effects of Y-27632 on pial microvessels. Y-27632 dilates only pial arterioles in a concentration-dependent manner, and most at a concentration of 10(-5) mol l(-1). Y-27632 is a potent cerebral pial arteriolar dilator but is not a venular dilator.

Cited by 3 publications

References 36 publications

The effects of Y-27632 on pial microvessels during global brain ischemia and reperfusion in rabbits

The effects of Y-27632 on pial microvessels during global brain ischemia and reperfusion in rabbits

Influence of pneumoperitoneum and head-down maneuver on the cerebral microvasculature in rabbits

Effects of β1-adrenergic receptor blockade on the cerebral microcirculation in the normal state and during global brain ischemia/reperfusion injury in rabbits

Contact Info

Product

Resources

About