thromboxane-a2 and Hyperemia

Topics: Animals; Antigens; Arachidonic Acids; Blood Circulation; Cell Movement; Epoprostenol; Guinea Pigs; Hyperemia; Lymph Nodes; Lymphocytes; Microcirculation; Prostaglandins E; Prostaglandins F; Rabbits; Sheep; Thromboxane A2

Modern functional imaging techniques of the brain measure local hemodynamic responses evoked by neuronal activity. Capillary pericytes recently were suggested to mediate neurovascular coupling in brain slices, but their role in vivo remains unexplored. We used two-photon microscopy to study in real time pericytes and the dynamic changes of capillary diameter and blood flow in the cortex of anesthetized mice, as well as in brain slices. The thromboxane A(2) analog, 9,11-dideoxy-9α,11α-methanoepoxy Prostaglandin F2α (U46619), induced constrictions in the vicinity of pericytes in a fraction of capillaries, whereas others dilated. The changes in vessel diameter resulted in changes in capillary red blood cell (RBC) flow. In contrast, during brief epochs of seizure activity elicited by local administration of the GABA(A) receptor antagonist, bicuculline, capillary RBC flow increased without pericyte-induced capillary diameter changes. Precapillary arterioles were the smallest vessels to dilate, together with penetrating and pial arterioles. Our results provide in vivo evidence that pericytes can modulate capillary blood flow in the brain, which may be important under pathological conditions. However, our data suggest that precapillary and penetrating arterioles, rather than pericytes in capillaries, are responsible for the blood flow increase induced by neural activity.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Arterioles; Bicuculline; Blood Flow Velocity; Brain; Capillaries; Cerebrovascular Disorders; Female; GABA-A Receptor Antagonists; Hyperemia; Male; Mice; Mice, Transgenic; Microscopy, Fluorescence, Multiphoton; Pericytes; Receptors, GABA-A; Thromboxane A2; Vasoconstrictor Agents; Vasodilation

The study was devised to assess the effects of a protein load (2 g/kg BW) on urinary prostaglandin E2 (PGE2), 6-keto-PGF1 alpha and thromboxane A2 (TxA2) in patients with renal failure of glomerular origin. To this end, 8 women with a glomerular filtration rate of 55 +/- 12 ml/min x 1.73 m2 underwent the following studies: study 1: control; study 2: meat meal; study 3: meat meal+intravenous aspirin; study 4: pretreatment with oral aspirin for 2 days+protocol in study 3. Glomerular hyperfiltration was seen after the meat meal (study 2) and was not suppressed by aspirin (studies 3 and 4). Urinary PGE2, 6-keto-PGF1 alpha and TxA2 increased after the meat meal in study 2 and were suppressed by aspirin in studies 3 and 4. The ratio between vasodilative (PGE2 + 6-keto-PGF1 alpha) and vasoconstrictive (TxA2) autacoids increased during the meat meal (study 2) and was suppressed when aspirin was injected at the time of the oral protein load, thus, the effect of aspirin was much greater for PGE2 and PGF1 alpha than for TxA2. These data do not support that urinary prostaglandin and TxA2 have a direct role in renal hyperfiltration due to an acute protein load.

Topics: Adult; Arachidonic Acids; Aspirin; Dietary Proteins; Dinoprost; Dinoprostone; Female; Glomerular Filtration Rate; Humans; Hyperemia; Kidney Diseases; Prostaglandins; Thromboxane A2

To assess the potential role of vasoactive cardiac eicosanoids in the modulation of coronary flow, we measure thromboxane(TX)B2, 6-keto-prostaglandin(PG)F1 alpha, PGE2 and sulphido-peptide leukotrienes (LTC4, D4, E4) in the coronary effluent of isolated perfused rat heart in both baseline and post-ischaemic conditions. Leukotrienes were undetectable. The order of production rate for the other eicosanoids was 6-keto-PGF1 alpha > TXB2 > PGE2. Production of such substances was increased about seven-fold over control after 5 min. global ischaemia; experiments with hypoxia showed that this was due to an actual increase in synthesis and not to a washout effect. A platelet source for TXB2 was excluded by 111In platelet labelling experiments. We assessed relative sensitivity to inhibition of cardiac TX synthesis relative to production of 6-keto-PGF1 alpha to inhibition by aspirin, ibuprofen, diclofenac and the specific thromboxane synthase inhibitor OKY-046. Aspirin, ibuprofen and diclofenac decreased 6-keto-PGF1 alpha production at a concentration always greater than required for a similar extent of TX inhibition. On the other hand a selective inhibition (> 90%) of TX was observed in the presence of OKY-046. Regression analysis of various 6-keto-PGF1 alpha/TXB2 ratios, as obtained in these different conditions, vs coronary flow, showed no correlation in baseline conditions, but a significant positive correlation (r = 0.59, P < 0.01) for post-ischaemic values. These data suggest a role for cardiac eicosanoids, including a non-platelet, cardiac-derived TX, in modulating the hyperaemic response in the isolated rat heart.

Topics: Animals; Blood Platelets; Coronary Circulation; Eicosanoids; Heart; Heart Rate; Hyperemia; Hypoxia; In Vitro Techniques; Indium Radioisotopes; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Rats; Rats, Wistar; Thromboxane A2; Thromboxanes

To determine the contribution of thromboxane (Tx) A2 release in reperfusion injury, 17 dogs were subjected to total coronary occlusion for 1 h and reperfusion for 1 h. Eleven dogs were treated with saline, and six were treated with selective TxA2 synthetase inhibitor U63,557A (5 mg/kg iv) 30 min before coronary artery occlusion. In all saline-treated dogs, peak reactive hyperemia after 10-s total coronary artery occlusion was diminished (P less than 0.01) after reperfusion. Myocardial segmental shortening was also reduced (9.8 +/- 1.9 to -6.7 +/- 2.0%, P less than 0.01) in the reperfused region. Reperfusion was associated with 737 +/- 343 premature ventricular contractions (PVCs) per hour. Histology revealed extensive myocardial infiltration and capillary plugging by leukocytes in the reperfused region. Myeloperoxidase, an index of leukocyte infiltration, was also increased (P less than 0.02) in the reperfused region. In the U63,557A-treated animals, serum and plasma TxB2 levels were markedly (P less than 0.02) reduced. Decrease in myocardial shortening fraction was less in U63,557A- than in saline-treated animals (P less than 0.05). The frequency of reperfusion PVCs was also significantly reduced (10 +/- 5 PVCs/h, P less than 0.02 compared with saline-treated dogs). However, peak reactive hyperemia was reduced similar to that in saline-treated dogs. Myocardial infiltration and capillary plugging by leukocytes in the reperfused regions was also similar in the U63,557A- and saline-treated dogs. These results indicate that treatment with U63,557A decreases reperfusion arrhythmias and preserves myocardial function. However, coronary reperfusion-induced deterioration in reactive hyperemia is not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Benzofurans; Coronary Disease; Dogs; Female; Heart; Hyperemia; Male; Myocardial Reperfusion; Myocardium; Peroxidase; Thromboxane A2; Thromboxane-A Synthase