| 1. |
- Cseplo, Peter, et al.
(författare)
-
Hemolyzed Blood Elicits a Calcium Antagonist and High CO2 Reversible Constriction via Elevation of [Ca2+]i in Isolated Cerebral Arteries
- 2017
-
Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 34:2, s. 529-534
-
Tidskriftsartikel (refereegranskat)abstract
- During acute subarachnoid hemorrhage, blood is hemolyzed, which is followed by a significant cerebrovascular spasm resulting in a serious clinical condition. Interestingly, however, the direct vasomotor effect of perivascular hemolyzed blood (HB) has not yet been characterized, preventing the assessment of contribution of vasoconstrictor mechanisms deriving from brain tissue and/or blood and development of possible treatments. We hypothesized that perivascular HB reduces the diameter of the cerebral arteries (i.e., basilar artery [BA]; middle cerebral artery [MCA]) by elevating vascular tissue [Ca2+](i) level. Vasomotor responses were measured by videomicroscopy and intracellular Ca2+ by the Fura2-AM ratiometric method. Adding HB to the vessel chamber reduced the diameter significantly (BA: from 264 +/- 7 to 164 +/- 11 mu m; MCA: from 185 +/- 15 to 155 +/- 14 mu m), which was reversed to control level by wash-out of HB. Potassium chloride (KCl), HB, serum, hemolyzed red blood cell (RBC), plasma, and platelet suspension (PLTs) elicited significant constrictions of isolated basilar arteries. There was a significant increase in K+ concentration in hemolyzed HB (7.02 +/- 0.22 mmol/L) compared to Krebs' solution (6.20 +/- 0.01 mmol/L). Before HB, acetylcholine (ACh), sodium-nitroprussid (SNP), nifedipin, and CO2 elicited substantial dilations in cerebral arteries. In contrast, in the presence of HB dilations to ACh, SNP decreased, but not to nifedipine and CO2. After washout of HB, nitric oxide-mediated dilations remained significantly reduced compared to control. HB significantly increased the ratiometric Ca signal, which returned to control level after washout. In conclusion, perivascular hemolyzed blood elicits significant-nifedipine and high CO2 reversible-constrictions of isolated BAs and MCAs, primarily by increasing intracellular Ca2+, findings that can contribute to the refinement of local treatment of subarachnoid hemorrhage.
|
|
| 2. |
- Czigler, Andras, et al.
(författare)
-
Prostaglandin E2, a postulated mediator of neurovascular coupling, at low concentrations dilates whereas at higher concentrations constricts human cerebral parenchymal arterioles
- 2020
-
Ingår i: Prostaglandins & other lipid mediators. - : Elsevier. - 1098-8823 .- 2212-196X. ; 146
-
Tidskriftsartikel (refereegranskat)abstract
- There is considerable controversy regarding the vasoactive action of prostaglandin E-2(PGE(2)). On the one hand, indirect evidence implicates that astrocytic release of PGE(2) contributes to neurovascular coupling responses mediating functional hyperemia in the brain. On the other hand, overproduction of PGE(2) was also reported to contribute to cerebral vasospasm associated with subarachnoid hemorrhage. The present study was conducted to resolve this controversy by determining the direct vasoactive effects of PGE(2) in resistance-sized human cerebral parenchymal arterioles. To achieve this goal PGE(2)-induced isotonic vasomotor responses were assessed in parenchymal arterioles isolated from fronto-temporo-parietal cortical tissues surgically removed from patients and expression of PGE(2) receptors were examined. In functionally intact parenchymal arterioles lower concentrations of PGE(2) (from 10(-8) to 10(-8) mol/l) caused significant, endothelium-independent vasorelaxation, which was inhibited by the EP4 receptor blocker BGC201531. In contrast, higher concentrations of PGE(2) evoked significant EP1-dependent vasoconstriction, which could not be reversed by the EP4 receptor agonist CAY10598. We also confirmed previous observations that PGE(2) primarily evokes constriction in intracerebral arterioles isolated from R. norvegicus. Importantly, vascular mRNA and protein expression of vasodilator EP4 receptors was significantly higher than that of vasoconstrictor EP1 receptors in human cerebral arterioles. PGE(2) at low concentrations dilates whereas at higher concentrations constricts human cerebral parenchymal arterioles. This bimodal vasomotor response is consistent with both the proposed vasodilator role of PGE(2) during functional hyperemia and its putative role in cerebral vasospasm associated with subarachnoid hemorrhage in human patients.
|
|
| 3. |
- Szarka, Nikolett, et al.
(författare)
-
Hypertension-Induced Enhanced Myogenic Constriction of Cerebral Arteries Is Preserved after Traumatic Brain Injury
- 2017
-
Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 34:14, s. 2315-2319
-
Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) was shown to impair pressure-induced myogenic response of cerebral arteries, which is associated with vascular and neural dysfunction and increased mortality of TBI patients. Hypertension was shown to enhance myogenic tone of cerebral arteries via increased vascular production of 20-hydroxyeicosatrienoic acid (HETE). This adaptive mechanism protects brain tissue from pressure/volume overload; however, it can also lead to increased susceptibility to cerebral ischemia. Although both effects may potentiate the detrimental vascular consequences of TBI, it is not known how hypertension modulates the effect of TBI on myogenic responses of cerebral vessels. We hypothesized that in hypertensive rats, the enhanced myogenic cerebrovascular response is preserved after TBI. Therefore, we investigated the myogenic responses of isolated middle cerebral arteries (MCA) of normotensive and spontaneously hypertensive rats (SHR) after severe impact acceleration diffuse brain injury. TBI diminished myogenic constriction of MCAs isolated from normotensive rats, whereas the 20-HETE-mediated enhanced myogenic response of MCAs isolated from SHRs was not affected by TBI. These results suggest that the optimal cerebral perfusion pressure values and vascular signaling pathways can be different and, therefore, should be targeted differently in normotensive and hypertensive patients following TBI.
|
|
