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Cerebral Arterioles (cerebral + arteriole)
Selected AbstractsRegional cerebral blood flow autoregulation in patients with fulminant hepatic failureLIVER TRANSPLANTATION, Issue 6 2000Fin Stolze Larsen The absence of cerebral blood flow autoregulation in patients with fulminant hepatic failure (FHF) implies that changes in arterial pressure directly influence cerebral perfusion. It is assumed that dilatation of cerebral arterioles is responsible for the impaired autoregulation. Recently, frontal blood flow was reported to be lower compared with other brain regions, indicating greater arteriolar tone and perhaps preserved regional cerebral autoregulation. In patients with severe FHF (6 women, 1 man; median age, 46 years; range, 18 to 55 years), we tested the hypothesis that perfusion in the anterior cerebral artery would be less affected by an increase in mean arterial pressure compared with the brain area supplied by the middle cerebral artery. Relative changes in cerebral perfusion were determined by transcranial Doppler,measured mean flow velocity (Vmean), and resistance was determined by pulsatility index in the anterior and middle cerebral arteries. Cerebral autoregulation was evaluated by concomitant measurements of mean arterial pressure and Vmean in the anterior and middle cerebral arteries during norepinephrine infusion. Baseline Vmean was lower in the brain area supplied by the anterior cerebral artery compared with the middle cerebral artery (median, 47 cm/s; range, 21 to 62 cm/s v 70 cm/s; range 43 to 119 cm/s, respectively; P < .05). Also, vascular resistance determined by pulsatility index was greater in the anterior than middle cerebral artery (median, 1.02; range 1.00 to 1.37 v 0.87; range 0.75 to 1.48; P < .01). When arterial pressure was increased from 84 mm Hg (range 57 to 95 mm Hg) to 115 mm Hg (range, 73 to 130 mm Hg) during norepinephrine infusion, Vmean remained unchanged in 2 patients in the anterior cerebral artery, whereas it increased in the middle cerebral artery in all 7 patients. In the remaining patients, Vmean increased approximately 25% in both the anterior and middle cerebral arteries. Thus, this study could only partially confirm the hypothesis that autoregulation is preserved in the brain regions supplied by the anterior cerebral artery in patients with FHF. Although the findings of this small study need to be further evaluated, one should consider that autoregulation may be impaired not only in the brain region supplied by the middle cerebral artery, but also in the area corresponding to the anterior cerebral artery. [source] Inhibition of NAD(P)H Oxidase Alleviates Impaired NOS-dependent Responses of Pial Arterioles in Type 1 Diabetes MellitusMICROCIRCULATION, Issue 7 2006WILLIAM G. MAYHAN ABSTRACT Objective: The goal was to identify the role of NAD(P)H oxidase in cerebrovascular dysfunction in type 1 diabetes mellitus (T1D). Methods: In a first series of studies, rats were assigned to nondiabetic, diabetic (streptozotocin; 50 mg/kg IP), nondiabetic-apocynin (40 mg/kg/day in drinking water)-treated and diabetic-apocynin-treated groups. Two to three months later, the authors examined in vivo responses of pial arterioles to nitric oxide synthase (NOS)-dependent (acetylcholine and adenosine diphosphate (ADP)) and -independent (nitroglycerin) agonists. Next, they used Western blot analysis to examine protein levels for subunits of NAD(P)H oxidase in cerebral microvessels and parietal cortex tissue of nondiabetic and diabetic rats. Finally, they measured superoxide production by parietal cortex tissue in nondiabetic and diabetic rats. Results: Acetylcholine- and ADP-induced dilatation of pial arterioles was impaired in diabetic compared to nondiabetic rats. In addition, while apocynin did not alter responses in nondiabetic rats, apocynin alleviated T1D-induced impairment of NOS-dependent vasodilatation. In addition, p47phox and gp91phox proteins were elevated in cerebral microvessels and parietal cortex tissue, respectively, of diabetic compared to nondiabetic rats. Further, basal production of superoxide was increased in diabetic compared to nondiabetic rats and apocynin decreased this basal production. Conclusions: The findings suggest that T1D impairs NOS-dependent reactivity of cerebral arterioles by a mechanism related to the formation of superoxide via activation of NAD(P)H oxidase. [source] Regulation of Blood,Brain Barrier PermeabilityMICROCIRCULATION, Issue 2 2001WILLIAM G. MAYHAN ABSTRACT The blood-brain barrier minimizes the entry of molecules into brain tissue. This restriction arises by the presence of tight junctions (zonulae occludens) between adjacent endothelial cells and a relative paucity of pinocytotic vesicles within endothelium of cerebral arterioles, capillaries, and venules. Many types of stimuli can alter the permeability characteristics of the blood-brain barrier. Acute increases in arterial blood pressure beyond the autoregulatory capacity of cerebral blood vessels, application of hyperosmolar solutions, application of various inflammatory mediators known to be elevated during brain injury, and/or activation of blood-borne elements such as leukocytes can produce changes in permeability of the blood-brain barrier. The second messenger systems that account for increases in permeability of the blood-brain barrier during pathophysiologic conditions, however, remain poorly defined. This review will summarize studies that have examined factors that influence disruption of the blood-brain barrier, and will discuss the contribution of various cellular second messenger pathways in disruption of the blood-brain barrier during pathophysiologic conditions. [source] Prevention of a hypoxic Ca2+i response by SERCA inhibitors in cerebral arteriolesBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2002C Guibert The aim of the study was to investigate the mechanism of a novel effect of hypoxia on intracellular Ca2+ signalling in rabbit cerebral arteriolar smooth muscle cells, an effect that was resistant to the L-type Ca2+ channel antagonist methoxyverapamil (D600). [Ca2+]i of smooth muscle cells in intact arteriolar fragments was measured using the Ca2+ -indicator dye fura-PE3. Hypoxia (PO2 10 , 20 mmHg) lowered basal [Ca2+]i but did not inhibit Ca2+ entry pathways measured by Mn2+ -quenching of fura-PE3. The effect of hypoxia was completely prevented by thapsigargin or cyclopiazonic acid, selective inhibitors of sarcoplasmic reticulum Ca2+ ATPase (SERCA). Since these inhibitors do not block Ca2+ extrusion or uptake via the plasma membrane, the data indicate that the effect of hypoxia depends on a functional sarcoplasmic reticulum. Because actions of nitric oxide (NO) on vascular smooth muscle are also prevented by SERCA inhibitors it was explored whether the effect of hypoxia occurred via modulation of endogenous NO release. Residual NOS-I and NOS-III were detected by immunostaining, and there were NO-dependent effects of NOS inhibitors on Ca2+i -signalling. Nevertheless, inhibition of endogenous NO production did not prevent the effect of hypoxia on [Ca2+]i. The experiments reveal a novel nitric oxide-independent effect of hypoxia that is prevented by SERCA inhibitors. British Journal of Pharmacology (2002) 135, 927,934; doi:10.1038/sj.bjp.0704547 [source] | ||||||||||