dinoprost and Hypercapnia

Carbon dioxide is an important vasodilator of cerebral blood vessels. Cerebral vasodilation mediated by adenosine triphosphate (ATP)-sensitive K+ channels has not been demonstrated in precapillary microvessel levels. Therefore, the current study was designed to examine whether ATP-sensitive K+ channels play a role in vasodilation induced by mild hypercapnia in precapillary arterioles of the rat cerebral cortex.. Brain slices from rat cerebral cortex were prepared and superfused with artificial cerebrospinal fluid, including normal (Pco2 = 40 mmHg; pH = 7.4), hypercapnic (Pco2 = 50 mmHg; pH = 7.3), and hypercapnic normal pH (Pco2 = 50 mmHg; pH = 7.4) solutions. The ID of a cerebral parenchymal arteriole (5-9.5 microm) was monitored using computerized videomicroscopy.. During contraction to prostaglandin F2alpha (5 x 10(-7) m), hypercapnia, but not hypercapnia under normal pH, induced marked vasodilation, which was completely abolished by the selective ATP-sensitive K+ channel antagonist glibenclamide (5 x 10(-6) m). However, the selective Ca2+-dependent K+ channel antagonist iberiotoxin (10(-7) m) as well as the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (10(-4) m) did not alter vasodilation. A selective ATP-sensitive K+ channel opener, levcromakalim (3 x 10(-8) to 3 x 10(-7) m), induced vasodilation, whereas this vasodilation was abolished by glibenclamide.. These results suggest that in parenchymal microvessels of the rat cerebral cortex, decreased pH corresponding with hypercapnia, but not hypercapnia itself, contributes to cerebral vasodilation produced by carbon dioxide and that ATP-sensitive K+ channels play a major role in vasodilator responses produced by mild hypercapnia.

Topics: Adenosine Triphosphate; Animals; Arterioles; Cerebral Cortex; Cerebrovascular Circulation; Dinoprost; Hydrogen-Ion Concentration; Hypercapnia; Male; NG-Nitroarginine Methyl Ester; Potassium Channels; Rats; Rats, Wistar; Vasodilation

We examined mean ( S.E.M.) changes in wall tension in isolated rat intrapulmonary arteries on switching from control conditions (pH 7.38 +/- 0.01; PCO2, 34.4 +/- 0.5 mmHg) to hypercapnic acidosis (pH change, -0.24 +/- 0.01; PCO2 change, +27.5 +/- 0.9 mmHg), isohydric hypercapnia (pH change, -0.02 +/- 0.01; PCO2 change, +28.5 +/- 0.8 mmHg) and normocapnic acidosis (pH change, -0.24 +/- 0.01; PCO2 change, -0.5 +/- 0.3). Arteries were submaximally preconstricted with prostaglandin F2 and changes in tension are expressed as a percentage of the 80 mM KCl-induced contraction (%Po). Mean changes in wall tension on switching to hypercapnic acidosis (+4.4 +/- 3.7 %Po), isohydric hypercapnia (+1.9 +/- 2.2 %Po) and normocapnic acidosis (-1.5 +/- 1.9 %Po) were not significantly different from the change observed on switching to control conditions (+3.5 +/- 1.1 %Po), and were unaltered by endothelial removal. In isolated carotid preparations, the change in tension in isohydric hypercapnia (-6.8 +/- 7.1 %Po) was not significantly different from that observed in control switches (+8.6 +/- 3.2 %Po). Significant reductions in tension (P < 0.001) were observed in hypercapnic (-42.9 +/- 7.8 %Po) and normocapnic acidosis (-36.4 +/- 9.0 %Po). These data suggest that intrapulmonary arteries are resistant to the vasodilator effects of extracellular acidosis observed in systemic (carotid) vessels.

Topics: Acidosis; Animals; Carbon Dioxide; Carotid Arteries; Dinoprost; Hydrogen-Ion Concentration; Hypercapnia; In Vitro Techniques; Male; Muscle, Smooth, Vascular; Phenylephrine; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Vasoconstriction

Responses of pial arterioles to topically applied arachidonic acid, conversion of exogenous arachidonic acid to prostanoids, and pial arteriolar dilation to hypercapnia were examined before and at progressive times after treatment with indomethacin (5 mg/kg i.v.) in chloralose-anesthetized newborn pigs with closed cranial windows. Before treatment with indomethacin, arachidonic acid and hypercapnia dilated pial arterioles and increased cortical periarachnoid cerebrospinal fluid concentrations of 6-keto-prostaglandin (PG) F1 alpha and PGE2. One h after indomethacin treatment, the dilations and prostanoid synthesis were blocked. By 2 h after indomethacin treatment, hypercapnia produced significant dilation of pial arterioles, and dilation to both stimuli had returned to preindomethacin levels by 3 h. Inhibition of conversion of exogenous arachidonic acid to prostanoids as monitored by increases in 6-keto-PGF1 alpha and PGE2 in cerebrospinal fluid under the window also was reversed by 3 h after treatment with indomethacin. Repeated indomethacin treatment again blocked dilations and conversion of arachidonic acid to prostanoids on the brain surface. The possibility of short duration of vascular effectiveness of indomethacin when it is administered systemically needs to be considered, both when it is used as a probe for understanding contributions of PGH synthase products to control of cerebral circulation and when it is used therapeutically in attempts to alter the newborn cerebral circulation.

Topics: Animals; Animals, Newborn; Arachidonic Acid; Arterioles; Cerebrovascular Circulation; Dinoprost; Dinoprostone; Hypercapnia; Indomethacin; Pia Mater; Swine; Vasodilation

Effects of ischemia (20 min) on cerebral cortical prostanoid synthesis and microvascular responses to hypercapnia and topical acetylcholine were examined in anesthetized newborn pigs. Pial arteriolar dilation in response to hypercapnia (10% CO2 ventilation, 10 min) was absent 2 h after ischemia and reversed toward constriction by 24 h postischemia. In sham control piglets, hypercapnia increased cortical periarachnoid fluid prostanoid concentrations. After ischemia, hypercapnia did not affect prostanoid concentrations on the brain surface. Acetylcholine (10(-3) M)-induced pial arteriolar constriction was reversed toward dilation 24 h after cerebral ischemia. Further, acetylcholine-induced prostanoid synthesis was markedly attenuated after ischemia. We conclude that cerebral ischemia-reperfusion alters cerebral prostanoid synthesis and microvascular control in newborn pigs. These abnormalities persist for at least 24 h.

Topics: 6-Ketoprostaglandin F1 alpha; Acetylcholine; Animals; Animals, Newborn; Brain; Brain Ischemia; Cerebrovascular Circulation; Dinoprost; Dinoprostone; Hypercapnia; Prostaglandins; Swine; Thromboxane B2

The role of prostaglandins in producing cerebrovasodilation during hypercapnia was tested in goats. Cerebral blood flow (CBF) changes with increasing arterial PCO2 were measured before and after prostaglandin synthesis inhibition with indomethacin or ibuprofen. Both drugs produced significant decreases in CBF under control anesthetized conditions but had no significant effect on the cerebrovascular response to increased arterial PCO2. The effects of direct intracerebrovascular infusion of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha) and prostacyclin were also measured. In the dose range tested (0.1-1) microgram/min) PGF2 alpha had no significantly greater than that produced by PGE2. The effectiveness of each compound in producing cerebrovascular changes is consistent with the endogenous distribution of prostaglandins within the brain. These results suggest that prostaglandins, particularly PGI2, may be important in modulating cerebrovascular tone but have no role in increasing CBF during hypercapnia.

Topics: Animals; Cerebrovascular Circulation; Dinoprost; Dinoprostone; Epoprostenol; Female; Goats; Hypercapnia; Ibuprofen; Indomethacin; Prostaglandins; Prostaglandins E; Prostaglandins F

Topics: Animals; Blood Gas Analysis; Cats; Cerebral Cortex; Dinoprost; Dinoprostone; Hypercapnia; Hypoxia; Prostaglandins; Prostaglandins E; Prostaglandins F