Role of prostaglandins in pial arteriolar response to CO2 and hypoxia

1980 ◽  
Vol 238 (2) ◽  
pp. H226-H230 ◽  
Author(s):  
E. P. Wei ◽  
E. F. Ellis ◽  
H. A. Kontos
Keyword(s):  
Arachidonic Acid ◽  
Parietal Cortex ◽  
Topical Application ◽  
Prostaglandin Synthesis ◽  
Vascular Responses ◽  
Cranial Window ◽  
Vasoconstrictor Response ◽  
Endogenous Prostaglandins ◽  
Inhibition Of Prostaglandin Synthesis

The effect of inhibition of prostaglandin synthesis on the pial arteriolar responses to arterial hypercapnia, hypocapnia, and hypoxia was studied in anesthetized cats equipped with a cranial window for the observation of the pial microcirculation of the parietal cortex. Inhibition of prostaglandin synthesis was achieved by intravenous administration of indomethacin (3 mg/kg) or AHR-5850 (2-amino-3-benzoylbenzeneacetic acid, 50 mg/kg). It was shown that the administration of these agents inhibited substantially the vasodilation in response to topical application of arachidonic acid (100--200 micrograms/ml). Inhibition of prostaglandin synthesis did not modify significantly the vasodilator responses to arterial hypercapnia or arterial hypoxia, nor the vasoconstrictor response to arterial hypocapnia. We conclude that endogenous prostaglandins are not mediators of these vascular responses in the pial microcirculation.

scholarly journals Role of Prostaglandins in the Response of the Cerebral Circulation to Carbon Dioxide in Conscious Rabbits

1983 ◽  
Vol 3 (3) ◽  
pp. 376-380 ◽  
Author(s):  
David W. Busija
Keyword(s):  
Blood Flow ◽  
Arachidonic Acid ◽  
Intravenous Administration ◽  
Cerebral Circulation ◽  
Prostaglandin Synthesis ◽  
Radioactive Microspheres ◽  
Cranial Window ◽  
Window Method ◽  
Conscious Rabbits

The role of prostaglandins in maintenance of resting cerebral blood flow (CBF) and in cerebral vasodilatation during hypercapnia remains controversial. The effect of indomethacin, a cyclo-oxygenase inhibitor, on CBF and cerebrovascular resistance (CVR) was examined in conscious animals. Regional and total CBF were measured with radioactive microspheres, and the efficacy of blockade of prostaglandin synthesis by indomethacin was examined by the cranial window method. CBF was measured in conscious rabbits with 15-μm radioactive microspheres during normocapnia (Pco2 ≈ 30 mm Hg) and hypercapnia (Pco2 ≈ 60 mm Hg), before and after intravenous administration of indomethacin (10 mg/kg) or vehicle (n = 6 for each). Thus, each animal served as its own control. CBF was 84 ± 6 and 190 ± 27 (mean ± SE) ml/min/100 g during normocapnia and hypercapnia, respectively, before indomethacin, and 78 ± 5 ml/min/100 g during normocapnia and 180 ± 16 ml/min/100 g during hypercapnia following indomethacin. Thus, indomethacin did not change normocapnic CBF. In addition, cerebrovascular responses during hypercapnia did not vary between the indomethacin and vehicle groups. Indomethacin did not attenuate increases in blood flow in any area of the brain, except slightly to cerebellum during hypercapnia. Indomethacin did not affect CVR during normocapnia or hypercapnia. The topical application of arachidonic acid (75 and 150 μg/mg), dissolved in cerebrospinal fluid, dilated pial arteries in a dose-dependent fashion. Intravenous administration of indomethacin (10 mg/kg) blocked vasodilatation produced by arachidonic acid by 87% (p < 0.05). Thus, indomethacin, at a dose that effectively inhibits prostaglandin synthesis, did not change resting CBF or CVR or attenuate the increase in CBF or decrease in CVR during hypercapnia. These findings suggest that prostaglandins do not contribute significantly to regulation of the cerebral circulation during normocapnia and hypercapnia.

Effects of indomethacin on cerebral blood flow during hypercapnia in cats

1983 ◽  
Vol 244 (4) ◽  
pp. H519-H524 ◽  
Author(s):  
D. W. Busija ◽  
D. D. Heistad
Keyword(s):  
Blood Flow ◽  
Arachidonic Acid ◽  
Cerebral Blood Flow ◽  
Intravenous Administration ◽  
Prostaglandin Synthesis ◽  
Pial Arteries ◽  
Cranial Window ◽  
Window Method ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Cerebral Vasodilatation

To study the contribution of prostaglandins to cerebral vasodilatation during hypercapnia, we inhibited prostaglandin synthesis with indomethacin. We measured cerebral blood flow (CBF) in anesthetized cats with 15-micrometers microspheres during normocapnia (PCO2 approximately 33 Torr), moderate hypercapnia (PCO2 approximately 49 Torr), and severe hypercapnia (PCO2 approximately 65 Torr) before and after intravenous administration of vehicle or indomethacin (3 and 10 mg/kg). Hypercapnia produced graded increments in blood flow to all areas of the brain. Administration of indomethacin did not change control CBF or significantly attenuate increases in CBF during hypercapnia. We examined efficacy and specificity of inhibition of prostaglandin synthesis by indomethacin using the cranial window method. Arachidonic acid (100 and 200 micrograms/ml) and acetylcholine (10(-7) and 10(-6)M or 10(-6) and 10(-5) M), dissolved in artificial cerebrospinal fluid, dilated pial arteries in a dose-dependent fashion. Intravenous administration of indomethacin blocked vasodilatation produced by arachidonic acid but did not affect the response to acetylcholine. Thus indomethacin, at a dose that effectively blocks prostaglandin synthesis, did not alter resting CBF or attenuate the increase in CBF during hypercapnia. This study suggests that steady-state cerebral vasodilatation during hypercapnia is largely preserved after inhibition of prostaglandin synthesis.

scholarly journals Role of Nitric Oxide in Regulation of Brain Stem Circulation during Hypotension

1997 ◽  
Vol 17 (10) ◽  
pp. 1089-1096 ◽  
Author(s):  
Kazunori Toyoda ◽  
Kenichiro Fujii ◽  
Setsuro Ibayashi ◽  
Tetsuhiko Nagao ◽  
Takanari Kitazono ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Brain Stem ◽  
Topical Application ◽  
Basilar Artery ◽  
Group Versus ◽  
Control Group ◽  
Cranial Window ◽  
Severe Hypotension ◽  
The Brain

We tested the hypothesis that nitric oxide (NO) plays a role in CBF autoregulation in the brain stem during hypotension. In anesthetized rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. During topical application of 10−5 mol/L and 10−4 mol/L Nω-nitro-L-arginine (L-NNA), a nonselective inhibitor of nitric oxide synthase (NOS), CBF started to decrease at higher steps of mean arterial blood pressure in proportion to the concentration of L-NNA in stepwise hypotension (45 to 60 mm Hg in the 10−5 mol/L and 60 to 75 mm Hg in the 10−4 mol/L L-NNA group versus 30 to 45 mm Hg in the control group). Dilator response of the basilar artery to severe hypotension was significantly attenuated by topical application of L-NNA (maximum dilatation at 30 mm Hg: 16 ± 8% in the 10−5 mol/L and 12 ± 5% in the 10−4 mol/L L-NNA group versus 34 ± 4% in the control group), but that of the branches was similar between the control and L-NNA groups. Topical application of 10−5 mol/L 7-nitro indazole, a selective inhibitor of neuronal NOS, did not affect changes in CBF or vessel diameter through the entire pressure range. Thus, endothelial but not neuronal NO seems to take part in the regulation of CBF to the the brain stem during hypotension around the lower limits of CBF autoregulation. The role of NO in mediating dilatation in response to hypotension appears to be greater in large arteries than in small ones.

Role of Endogenous Prostaglandins in Duodenal Alkaline Response to Luminal Hydrochloric Acid or Arachidonic Acid in Conscious Dogs

Digestion ◽  
1986 ◽  
Vol 34 (4) ◽  
pp. 268-274 ◽  
Author(s):  
S.J. Konturek ◽  
J. Bilski ◽  
J. Tasler ◽  
J.W. Konturek ◽  
W. Bielański ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Hydrochloric Acid ◽  
Conscious Dogs ◽  
Endogenous Prostaglandins

Arteriolar responses to extracellular ATP in striated muscle

1997 ◽  
Vol 272 (4) ◽  
pp. H1886-H1891 ◽  
Author(s):  
W. T. McCullough ◽  
D. M. Collins ◽  
M. L. Ellsworth
Keyword(s):  
Striated Muscle ◽  
Atp Release ◽  
Cheek Pouch ◽  
Retractor Muscle ◽  
Vascular Responses ◽  
Local Tissue ◽  
Dilatory Response ◽  
Vasoconstrictor Response

Blood flow and its distribution must be appropriately regulated to ensure that perfusion is matched to local tissue demands. We investigated the role of ATP in triggering a conducted alteration in arteriolar diameter in the Saran-covered cheek pouch retractor muscle of anesthetized hamsters (n = 60). Vascular responses were observed using in vivo video microscopy upstream from the site of micropressure application of ATP (10(-8)-10(-4) M) either into the lumen or just outside the wall of first- and second-order arterioles. The role of nitric oxide (NO) in the vascular responses to ATP was determined by inhibiting NO synthase activity with N(omega)-nitro-L-arginine methyl ester (L-NAME) with and without coadministration of an excess of L-arginine. Intraluminal application of ATP led to a concentration-dependent vasodilation, which was conducted upstream along the arteriole. The dilatory response was blocked by systemic pretreatment with L-NAME and was maintained in the presence of an excess of L-arginine. In contrast, ATP introduced extraluminally resulted in a conducted vasoconstrictor response that was enhanced by pretreatment with L-NAME. The dilator response to intraluminal ATP, in the context of ATP release from erythrocytes under conditions associated with decreased supply relative to demand, supports a role for the erythrocyte in communicating local tissue needs to the vasculature, enabling the appropriate matching of oxygen supply to demand.

Evidence that prostaglandins are local regulatory agents in canine ileal circular muscle

1984 ◽  
Vol 246 (4) ◽  
pp. G361-G371 ◽  
Author(s):  
K. M. Sanders
Keyword(s):  
Action Potentials ◽  
Circular Muscle ◽  
Prostaglandin Synthesis ◽  
Mechanical Activity ◽  
Mechanical Effects ◽  
Endogenous Prostaglandin ◽  
Endogenous Prostaglandins ◽  
Electrical Activities ◽  
Electrical And Mechanical Activities

Studies were performed to determine the role of endogenous prostaglandins (PG) in regulating mechanical and electrical activities of canine ileal circular muscles. Indomethacin, a prostaglandin synthesis blocker, enhanced the amplitude of spontaneous and acetylcholine-stimulated contractions. The increase in mechanical activity caused by indomethacin was accompanied by decreased release of 6-keto-PGF1 alpha, the spontaneous metabolite of prostacyclin, from the muscle. The electrical mechanisms responsible for the changes in mechanical activity caused by indomethacin were investigated by intracellular measurement of electrical activity. The enhanced contractions due to indomethacin correlated with enhanced electrical slow-wave amplitude and generation of action potentials. After indomethacin treatment muscles were exposed to several exogenous prostaglandins to determine which of these compounds might reverse the mechanical effects of indomethacin. Prostacyclin reversed the effects of indomethacin, and PGE2 reversed some of the effects of indomethacin. Prostacyclin also decreased the amplitude of electrical slow waves and abolished action potentials. These electrical effects were associated with decreased contractile amplitude. It is concluded that the dominant prostaglandin responsible for the "prostaglandin effect" in canine ileal circular muscle must be inhibitory to spontaneous and acetylcholine-stimulated contractions. The mechanical effects attributed to endogenous prostaglandin appear to be due to an electrical mechanism. Based on the evidence presented prostacyclin emerges as the most likely candidate for the role of "dominant" prostaglandin, but PGE2 may also contribute as a modulator of electrical and mechanical activities.

scholarly journals Role of Prostaglandins in Blood-Induced Vasoconstriction of Canine Cerebral Arteries

1988 ◽  
Vol 8 (1) ◽  
pp. 109-115 ◽  
Author(s):  
Sally A. Lang ◽  
Michael B. Maron
Keyword(s):  
Arachidonic Acid ◽  
Vascular Resistance ◽  
Topical Application ◽  
Cerebral Arteries ◽  
Cyclooxygenase Inhibitors ◽  
Prostaglandin E ◽  
Constant Flow ◽  
Thromboxane Synthetase ◽  
By Products

We tested the hypothesis that the vasoconstriction produced by the application of blood to the adventitial surfaces of the vessels of an isolated perfused canine circle of Willis preparation was mediated by products of prostaglandin metabolism. In this preparation (perfused at constant flow and outflow pressure), topical application of blood produced an average 16.6 ± 1.8 (SE) mm Hg increase in inflow pressure. This response could be prevented with four structurally dissimilar cyclooxygenase inhibitors (aspirin, indomethacin, ibuprofen, and meclofenamate), suggesting that the blood-induced increase in vascular resistance was mediated by prostaglandins. Imidazole, an inhibitor of thromboxane synthetase, had no effect on the blood response. Further support for the involvement of prostaglandins in this response was provided by additional experiments in which either arachidonic acid, prostaglandin E2 (PGE2), or PGF2α were administered. All three treatments produced vasoconstriction. These results suggest that the vessels of this preparation are capable of synthesizing vasoconstrictor prostaglandins and indicate that they are reactive to known vasoactive prostaglandins.

Prostanoids promote pial arteriolar dilation and mask constriction to oxytocin in piglets

1993 ◽  
Vol 264 (4) ◽  
pp. H1023-H1027
Author(s):  
D. W. Busija ◽  
I. Khreis ◽  
J. Chen
Keyword(s):  
Cerebrospinal Fluid ◽  
Intravital Microscopy ◽  
Prostaglandin Synthesis ◽  
Pial Arterioles ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Csf Levels ◽  
Low Levels ◽  
Arteriolar Diameter ◽  
Baseline Diameter

We determined effects of oxytocin on piglet pial arterioles and the role of prostanoids in mediating arteriolar responses. Anesthetized piglets were equipped with closed cranial windows, and arteriolar diameter was measured using intravital microscopy. Pial arterioles were exposed to 10(-10) to 10(-4) M oxytocin. Cerebrospinal fluid (CSF) levels of prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were determined using radioimmunoassay. Baseline diameter was 110 +/- 4 microns and increased to 120 +/- 6 microns at 10(-8) M (9 +/- 3%, n = 20). CSF levels of PGE2 were 697 pg/ml during baseline and increased to 1,685 +/- 316 pg/ml during 10(-6) M, 2,243 +/- 327 pg/ml during 10(-5) M, and 2,941 +/- 500 pg/ml during 10(-4) (n = 6). CSF levels of 6-keto-PGF1 alpha were 354 +/- 73 pg/ml during baseline and increased to 734 +/- 168 pg/ml at 10(-5) M and to 836 +/- 167 pg/ml at 10(-4) M (n = 5). After inhibition of prostaglandin synthesis by indomethacin (5 mg/kg i.v.), oxytocin constricted at all doses, starting at 10(-10) M (5 +/- 2%) and continuing to constrict at 10(-4) M (24 +/- 2%, n = 14). We conclude that: 1) piglet pial arterioles respond to relatively low levels of oxytocin, 2) local presence and/or production of prostanoids promotes dilation, and 3) endogenous prostanoids prevent constriction of pial arterioles to oxytocin. Our results suggest that oxytocin could play a role in the regulation of cerebral hemodynamics.

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