Effects of prostaglandin F2 alpha and thromboxane A2 analogue on bovine cerebral arterial tone and calcium fluxes.

Abstract

We determined sources of activator calcium for prostanoid-induced cerebrovascular constriction by measuring isometric tension and calcium-45 ("Ca) fluxes in bovine middle cerebral arteries. Constriction induced by prostaglandin F^ or the stable thromboxane A 2 analogue SQ-26,655 was near-maximally inhibited in calcium-deficient solutions but only partially inhibited by calcium antagonists (10~! M verapamil or 33xlO~7 M nifedipine). Studies of ^Ca binding at different external Ca 2+ concentrations showed that cerebral arteries possess two calcium binding sites, a high-affinity site and a low-affinity site. Each prostanoid significantly increased low-affinity ^Ca uptake (external Ca 2+ concentration = 1.2 mmol/l) during 5 minutes of '"Ca loading; for prostaglandin F^ ^Ca uptake increased from 69 to 108 nmol/g and for SQ-26,655, from 78 to 141 nmol/g. The prostanoid-induced increases in low-affinity ^Ca uptake were completely abolished by pretreatment with verapamil or nifedipine. Prostaglandin F^, SQ-26,655, verapamil, and nifedipine had no effect on high-affinity ^Ca uptake (external Ca J+ concentration=45 /umol/l) or ^Ca efflux (after 60 minutes' preincubation in calcium-deficient media). Prostaglandin F^ and SQ-26,655 each appear to constrict cerebral arteries by two mechanisms: first, by promoting calcium uptake from low-affinity binding sites through receptor-operated channels sensitive to the calcium antagonists, and second, by releasing calcium from depletable internal stores. (Stroke 1991;22:66-72)

Flurbiprofen axetil attenuates cerebral ischemia/reperfusion injury by reducing inflammation in a rat model of transient global cerebral ischemia/reperfusion

“…Synthesis of TXA2 activation could lead to an imbalance of TXA2/PGI2 that induces capillary blockade by platelet, leukocyte, and sediments of fibrin. These events result in a phenomenon of ‘no reflow’ and microcirculation disturbance in the brain tissue, which may aggravate cerebral secondary injury [48].…”

Proinflammatory and Vasoactive Effects of Aβ in the Cerebrovasculature

“…More recently, we have characterized a proinflammatory cascade that contributes to Aβ's vasoactive property 37,38. Interestingly, eicosanoids (end products of Aβ's stimulation of a proinflammatory pathway) are important modulators of cerebral vasotonus; for example, PGF 2α can directly induce vasoconstriction in the cerebrovasculature 43,64. Inflammation has been suggested to be a key factor in initiating AD dementia.…”

Effect of Latanoprost on Regional Blood Flow and Capillary Permeability in the Monkey Eye

“…7,8 Prostaglandin F 2␣ is a known vasodilator but can also cause vasoconstriction (eg, in the brain). [9][10][11][12] The question has, therefore, arisen whether latanoprost could induce vasoconstriction in the eye, particularly in the posterior pole, that could be detrimental and aggravate the glaucomatous disease. 13 Conversely, it may also be of interest to know whether latanoprost induces increased blood flow in the eye, and particularly in the posterior pole, which could be advantageous in the treatment of glaucoma.…”