Prostacyclin and cerebral vessel relaxation

Paul, Kamal S.; Whalley, Eric T.; Förster, Christine; Lye, R. H.; Dutton, John

doi:10.3171/jns.1982.57.3.0334

Cited by 45 publications

(15 citation statements)

References 27 publications

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“…In almost all studies of cerebral arteries, including those in humans, Ang II produced constriction (Edvinsson et al, 1979;Paul et al, 1982;Shimizu et al, 1986;Juul et al, 1987;Whalley et al, 1985;Naveri et al, 1994;Stenman and Edvinsson, 2004;Krueger and Cook, 1985;Toda et al, 1990;Toda and Hayashi, 1979). In the present study, we found that Ang II was a potent constrictor of the basilar artery in male mice.…”

Section: Effects Of Angiotensin II In the Cerebral Circulationmentioning

confidence: 99%

Cerebral Vascular Effects of Angiotensin II: New Insights from Genetic Models

Faraci

Lamping

Modrick

et al. 2005

J Cereb Blood Flow Metab

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Very little is known regarding the mechanisms of action of angiotensin II (Ang II) or the consequences of Ang II-dependent hypertension in the cerebral circulation. We tested the hypothesis that Ang II produces constriction of cerebral arteries that is mediated by activation of AT 1A receptors and Rho-kinase. Basilar arteries (baseline diameter B130 lm) from mice were isolated, cannulated and pressurized to measure the vessel diameter. Angiotensin II was a potent constrictor in arteries from male, but not female, mice. Vasoconstriction in response to Ang II was prevented by an inhibitor of Rho-kinase (Y-27632) in control mice, and was reduced by B85% in mice deficient in expression of AT 1A receptors. We also examined the chronic effects of Ang II using a model of Ang II-dependent hypertension, mice which overexpress human renin (R þ ) and angiotensinogen (A þ ). Responses to the endothelium-dependent agonist acetylcholine were markedly impaired in R þ A þ mice (Po0.01) compared with controls, but were restored to normal by a superoxide scavenger (PEG-SOD). A-23187 (another endothelium-dependent agonist) produced vasodilation in control mice, but no response or vasoconstriction in R þ A þ mice. In contrast, dilation of the basilar artery in response to a NO donor (NONOate) was similar in R þ A þ mice and controls. Thus, Ang II produces potent constriction of cerebral arteries via activation of AT 1A receptors and Rho-kinase. There are marked gender differences in cerebral vascular responses to Ang II. Endothelial function is greatly impaired in a genetic model of Ang II-dependent hypertension via a mechanism that involves superoxide.

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Section: Effects Of Angiotensin II In the Cerebral Circulationmentioning

confidence: 99%

Cerebral Vascular Effects of Angiotensin II: New Insights from Genetic Models

Faraci

Lamping

Modrick

et al. 2005

J Cereb Blood Flow Metab

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“…8 Changes in 6-keto-PGF la biosynthesis and release have been studied only in experimental cerebral ischemia 12 ; the variation of its synthesis has been reported to be region-specific (in the hippocampus) and closely time-dependent (increased 30 minutes after reflow, and decreased to 60% of control at 24 hours). Prostacyclin is involved in regulation of the microcirculation, is synthesized by endothelial cells, has a marked vasodilating effect, 18 ' 38 and prevents blood-brain barrier derangement 39 and impairment due to postischemic brain reperfusion. 840 In our present study, the release of 6-keto-PGF, a was significantly reduced 1 and 6 hours after SAH; we hypothesize that at this time the endothelial damage caused by the SAH exerted an inhibitory effect on cyclooxygenase enzyme in the arterial wall.…”

mentioning

confidence: 99%

Arachidonic acid metabolism and pathophysiologic aspects of subarachnoid hemorrhage in rats.

Gaetani

Marzatico

Baena

et al. 1990

Stroke

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We studied the ex vivo production of prostaglandin D 2 , prostaglandin E^, 6-ketoprostaglandin F la , and leukotriene C 4 in the brain tissue of rats subjected to experimental subarachnoid hemorrhage. The ex vivo method allows the study of arachidonic acid metabolites released from brain slices at different times after subarachnoid hemorrhage induction and reflects the residual capacity for arachidonic acid metabolism after the pathologic event The rats were sacrificed 30 minutes, 1 and 6 hours, and 2 days after subarachnoid hemorrhage was induced by the injection of 0 JO ml autologous arterial blood into the cisterna magna. Concentration of prostaglandin D 2 and 6-ketoprostaglandin F, a was increased significantly relative to control 2 days after induction. The concentration of prostaglandin E 2 was increased significantly 6 hours after induction, while ex vivo production of leukotriene C 4 was increased significantly at 1 and 6 hours and 2 days. The correlation between these results and the occurrence of vasospasm after subarachnoid hemorrhage is discussed. The results obtained from the ex vivo incubation of brain tissue slices after experimental subarachnoid hemorrhage suggest that after the hemorrhage there is a significant modification of brain eicosanoid metabolism, which could be of great importance in interpreting the pathogenesis of subarachnoid hemorrhage-related neuronal impairment (Stroke 1990;21:328-332)

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“…16,17 Prostacyclin in corresponding low concentrations has also been shown to improve vessel diameter in vitro. 7,8 Thus, a dose of 1 to 2 ng/kg per minute might be effective while the risk of the well-known dose-dependent adverse effects could be minimized. The low-dose prostacyclin used also fulfils the theoretical rationale for treatment by compensating for a reduced endogenous production which has been demonstrated in an animal SAH model.…”

Section: Prostacyclin Dose Rationalementioning

confidence: 99%

“…It is a potent vasodilator and inhibitor of leukocyte activation, platelet aggregation, and leukocyte-endothelial interactions, all of which are properties with a hypothetical impact on the development of DIND. 5 Animal studies and in vitro studies have demonstrated positive effects of prostacyclin on cerebral blood flow (CBF) and vasospasm, [6][7][8][9][10] and an imbalance in the prostacyclin-prostaglandin ratio has been proposed as a cause of vasospasm. 6,11 Although results from in vitro and animal studies are promising, few studies exist that investigate the possible effects of prostacyclin on cerebral…”

mentioning

confidence: 99%

Effects of Prostacyclin on Cerebral Blood Flow and Vasospasm After Subarachnoid Hemorrhage

Rasmussen

Wetterslev

Stavngaard

et al. 2015

Stroke

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Background and Purpose-Delayed ischemic neurological deficits (DINDs) are a major contributing factor for poor outcome in patients with subarachnoid hemorrhage. In this trial, we investigated the therapeutic potential of prostacyclin, an endogen substance with known effect on vascular tone and blood flow regulation, on factors related to DIND. Methods-This trial is a single-center, randomized, blinded, clinical, pilot trial with 3 arms. Ninety patients were randomized to continuous infusion of prostacyclin 1 ng/kg per minute, prostacyclin 2 ng/kg per minute, or placebo. The intervention was initiated day 5 after subarachnoid hemorrhage and discontinued day 10. Primary outcome was the difference in change from baseline in global cerebral blood flow. Secondary outcome measures were occurrence of DIND, angiographic vasospasm, and clinical outcome at 3 months. Results-No statistically significant difference in change of global cerebral blood flow was found between the intervention groups. The observed incidence of DIND and angiographic vasospasm was markedly higher in the placebo group, although this difference was not statistically significant. No statistically significant differences in safety parameters or clinical outcome were found between the 3 groups. Conclusions-Administration of prostacyclin to patients with subarachnoid hemorrhage may be safe and feasible. Global cerebral blood flow after subarachnoid hemorrhage is not markedly affected by administration of prostacyclin in the tested dose range. It may be possible that the observed reduction in the point estimates of DIND and vasospasm in the prostacyclin groups represents an effect of prostacyclin as this trial was not powered to investigate the effect of prostacyclin on these outcomes. 14 In this randomized, placebo-controlled trial, we investigate the possible pharmacodynamic effects of prostacyclin on the human brain after SAH. The full background and trial protocol have been published previously. 14 Methods Overview and Randomization ProcedureThis trial is a single-center, randomized, placebo-controlled, parallel group, blinded, clinical, pilot trial. The trial was conducted at Rigshospitalet, Copenhagen University Hospital, Neurointensive Care Unit, Denmark, and was approved by the Danish ethical committee on Human Research (ref No. H-1-2011-087), the Danish Medicines Agency (EudraCT 2011-002798-5), and registered on www.clinicaltrials.gov (ref No. NCT01447095). The inclusion criteria were aneurysmal SAH treated with coiling or surgery, a World Federation of Neurological Surgeons score between 1 and 4 and Fisher grade 3 or 4. Exclusion criteria were previous SAH, pregnancy/lactation, renal failure, heart failure, bleeding diathesis, major complication during endovascular procedure or surgery, or SAH on the basis of posterior inferior cerebellar artery aneurysm. A total of 90 patients were randomized to a continuous infusion of epoprostenol 1 ng/kg per minute, epoprostenol 2 ng/kg per minute, or placebo (drug solvent). Trial medication was initiated d...

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Prostacyclin and cerebral vessel relaxation

Cited by 45 publications

References 27 publications

Cerebral Vascular Effects of Angiotensin II: New Insights from Genetic Models

Cerebral Vascular Effects of Angiotensin II: New Insights from Genetic Models

Arachidonic acid metabolism and pathophysiologic aspects of subarachnoid hemorrhage in rats.

Effects of Prostacyclin on Cerebral Blood Flow and Vasospasm After Subarachnoid Hemorrhage

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