Investigation of the role of prostaglandins in nitroglycerin-induced relaxation of isolated rabbit blood vessels

1983 ◽  
Vol 61 (6) ◽  
pp. 554-560 ◽  
Author(s):  
Brian M. Bennett ◽  
Joyce A. Moffat ◽  
Paul W. Armstrong ◽  
Gerald S. Marks
Keyword(s):  
Effective Dose ◽  
Blood Vessels ◽  
Prostaglandin Synthesis ◽  
Mesenteric Arteries ◽  
Krebs Solution ◽  
Rabbit Blood ◽  
Inhibit Prostaglandin Synthesis ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Stimulation Of

The effect of inhibition of prostaglandin synthesis on nitroglycerin-induced relaxation was examined in isolated rabbit mesenteric and celiac arterial rings. An indomethacin dose of 5 μM was selected as adequate to inhibit prostaglandin synthesis as this dose prevented relaxation of the arterial rings by sodium arachidonate (3.3 μM) and by bradykinin, a peptide thought to induce vasodilation via stimulation of prostaglandin synthesis. Following 20 min pretreatment with indomethacin (5 μM), indomethacin solvent, or Krebs solution (control), the arterial rings were contracted submaximally with phenylephrine (0.5–10 μM). The degree of inhibition of phenylephrine-induced tone produced after cumulative additions of nitroglycerin (10−10 – 5 × 10−7 M) was assessed. In control celiac and mesenteric rings the responses to nitroglycerin were as follows: mean effective dose (ED50), 5.6 × 109 ± 4.5 × 10−9 M (SD) and 1.1 × 10−8 ± 5 × 10−9 M (SD), respectively; maximum relaxation, 97 ± 3% (SD) and 93 ± 7% (SD), respectively. Neither indomethacin nor indomethacin solvent affected the ED50 or maximum relaxation with nitroglycerin. We conclude that nitroglycerin-induced relaxation of rabbit celiac and mesenteric arteries appears to be mediated through a mechanism other than stimulation of prostaglandin synthesis.

Expression of Cell Cycle Proteins P21 waf1/Cip1 , P27 kip1 , Cyclin D1 and CDK4 in Blood Vessels of Angiotensin II-Infused Rats. Role of AT 1 Receptors.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 707-707
Author(s):  
Quy N Diep ◽  
Mohammed El Mabrouk ◽  
Rhian M Touyz ◽  
Ernesto L Schiffrin
Keyword(s):  
Cell Cycle ◽  
Angiotensin Ii ◽  
Dna Synthesis ◽  
Cyclin D1 ◽  
Blood Vessels ◽  
Thymidine Incorporation ◽  
Mesenteric Arteries ◽  
Ang Ii

P79 Angiotensin II (Ang II) is an important modulator of cell growth via AT 1 receptors, as demonstrated both in vivo and in vitro . Here, we investigated the role of different proteins involved in the cell cycle, including cyclin D1, cyclin-dependent kinase 4 (cdk4) and cdk inhibitors p21 and p27 in blood vessels of Ang II-infused rats and the effect therein of the AT 1 receptor antagonist losartan. Male Sprague Dawley rats were infused for 7 days with Ang II (120 ng/kg/min s.c.) and/or treated with losartan (10 mg/kg/day orally). DNA synthesis in mesenteric arteries was evaluated by radiolabeled 3 H-thymidine incorporation. The expression of p21, p27, cyclin D1, cdk4 and E2F, which play critical roles during G1-phase of the cell cycle process, was examined by Western blot analysis. Tail cuff systolic blood pressure (mmHg) was elevated (p<0.05, n=9) in Ang II-infused rats (161.3±8.2) vs. controls (110.1±5.3) and normalized by losartan (104.4±3.2). Radiolabeled 3 H-thymidine incorporation (cpm/100 μg DNA) showed that Ang II-infusion significantly increased DNA synthesis (152±5 vs. 102±6, p<0.05). Expression of p21 and p27 was significantly decreased in the Ang II group to 23.2±10.4% and 10.3±5.3% of controls, respectively, whereas expression of cyclin D1 and cdk4 was significantly increased in the Ang II group to 213.7±8% and 263.6±37% of controls, respectively. These effects induced by Ang II infusion was normalized in the presence of losartan. Ang II had no effect on the expression of E2F. Thus, when AT 1 receptors are stimulated in vivo , DNA synthesis is enhanced in blood vessels by activation of cyclin D1 and cdk4. Reduction in cell cycle kinase inhibitors p21 and p27 may contribute to activation of growth induced by in vivo AT 1 receptor stimulation.

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.

Furosemide action on collecting ducts: effect of prostaglandin synthesis inhibition

1983 ◽  
Vol 244 (6) ◽  
pp. F666-F673 ◽  
Author(s):  
D. R. Wilson ◽  
U. Honrath ◽  
H. Sonnenberg
Keyword(s):  
Collecting Duct ◽  
Prostaglandin Synthesis ◽  
Water Reabsorption ◽  
Inner Medullary Collecting Duct ◽  
Nephron Segments ◽  
Inhibit Prostaglandin Synthesis ◽  
Collecting Ducts ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Medullary Collecting Duct ◽  
Furosemide Administration

The effect of furosemide on inner medullary collecting duct chloride reabsorption has not been determined, and the blunting of furosemide action by drugs that inhibit prostaglandin synthesis, while known to occur, has not been examined in detail. The effect of indomethacin and meclofenamate on furosemide diuresis was studied in the rat using clearance and collecting duct microcatheterization methods. Furosemide-treated control animals showed complete inhibition of chloride, sodium, and water reabsorption in the inner medullary collecting duct. Rats given indomethacin or meclofenamate before and during furosemide administration showed marked reduction of the chloriuresis, natriuresis, and diuresis. Reduced delivery of sodium and chloride to the beginning of the inner medullary collecting duct, associated with a decrease in glomerular filtration rate and increased reabsorption in more proximal nephron segments, was largely responsible for the reduced natriuresis and chloriuresis during inhibition of prostaglandin synthesis. In addition, indomethacin increased collecting duct NaCl reabsorption toward normal, but meclofenamate showed no such effect. The results indicate that furosemide inhibits medullary collecting duct reabsorption of chloride, sodium, and water in the rat. The blunting of diuretic action seen with inhibition of prostaglandin synthesis is largely, although not entirely, due to effects of indomethacin and meclofenamate on furosemide action at nephron sites proximal to the collecting duct.

Effects of histidine on vasopressin action: role of decreased prostaglandin production

1988 ◽  
Vol 255 (4) ◽  
pp. F685-F689
Author(s):  
C. P. Carvounis ◽  
E. T. Schroeder ◽  
P. Cushley ◽  
P. Hueber ◽  
D. Patchin
Keyword(s):  
Prostaglandin E2 ◽  
Water Movement ◽  
Imidazole Ring ◽  
Prostaglandin Synthesis ◽  
Pge2 Production ◽  
Toad Bladder ◽  
Prostaglandin Production ◽  
Luminal Membrane ◽  
Inhibition Of Prostaglandin Synthesis

Addition of histidine to the serosal bath of the toad bladder increases the hydrosmotic response of vasopressin in this tissue. Because this represents primarily the effect of the imidazole ring of histidine, which is a known inhibitor of the production of prostaglandins, we evaluated whether histidine increases the response to vasopressin through decreased prostaglandin production. Histidine increases the response to vasopressin much more than 10(-5) M naproxen, even though the latter was equipotent to histidine in reducing prostaglandin E2 (PGE2) production. Furthermore, histidine was additive to naproxen in increasing the hydrosmotic effect of vasopressin, without causing a further decrease in PGE2 production. These findings suggest that histidine has an effect over and above that due to inhibition of prostaglandin synthesis. Our results suggest that histidine enhances the permeability of the tissue beneath the luminal membrane, an effect not found with naproxen. We propose that histidine increases the hydrosmotic response to vasopressin through at least two distinct mechanisms: 1) it decreases prostaglandin synthesis and thus increases luminal permeability; 2) it decreases the resistance to water movement of the tissues beneath the luminal membrane.

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.

Stimulation of apoptosis by sulindac and piroxicam

1998 ◽  
Vol 95 (3) ◽  
pp. 385-388 ◽  
Author(s):  
William R. WADDELL
Keyword(s):  
Acetic Acid ◽  
Mitochondrial Membrane ◽  
Prostaglandin Synthesis ◽  
Intermembrane Space ◽  
Colon Polyps ◽  
Inner Mitochondrial Membrane ◽  
Normal Cells ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Stimulation Of

1.Sulindac, cis-5-fluoro-2-methyl-1-(p-methylsulphinylbenzylidene)indene-3-acetic acid, inhibits growth of colon polyps and cancers. This effect has been attributed to inhibition of prostaglandin synthesis but more recent observations indicate that, in vitro, cells that do not have cyclo-oxygenase nor RNA for synthesis of such enzymes are affected by sulindac. Therefore the presumptive effect is probably not correct. 2.It has also been found that sulindac stimulates apoptosis. It is herein postulated that in tumour cells such effects may be due to interaction of the anionic form of the drug with protons in the intermembrane space of mitochondria to disrupt the potential across the inner mitochondrial membrane and thereby initiate apoptosis. Normal cells are not affected.

Stimulation of Hematopoiesis in Untreated and Cyclophosphamide Treated Mice by the Inhibition of Prostaglandin Synthesis

1986 ◽  
Vol 8 (3) ◽  
pp. 299-313 ◽  
Author(s):  
Daniel A. Nikcevich ◽  
M. Rita Young ◽  
Nancy K. Ellis ◽  
Marilyn Newby ◽  
H. Terry Wepsic
Keyword(s):  
Prostaglandin Synthesis ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Stimulation Of

Role of cGMP as a mediator of nerve-induced motor functions of the opossum esophagus

2000 ◽  
Vol 279 (3) ◽  
pp. G567-G574 ◽  
Author(s):  
W. Shahin ◽  
J. A. Murray ◽  
E. Clark ◽  
J. L. Conklin
Keyword(s):  
Selective Inhibitor ◽  
Krebs Solution ◽  
Electrical Field ◽  
Exogenous Nitric Oxide ◽  
Esophageal Sphincter ◽  
Displacement Transducers ◽  
Force Displacement ◽  
Esophageal Muscle ◽  
Stimulation Of

Stimulation of esophageal nerves produces biphasic relaxation of the lower esophageal sphincter (LES) and an off response of circular esophageal muscle. Previously, we proposed that cGMP mediates nerve-induced hyperpolarization of circular LES muscle but not LES relaxation. These experiments explore whether cGMP mediates LES relaxation or the off response. Strips of muscle from the opossum esophagus and LES were connected to force-displacement transducers, placed in tissue baths containing oxygenated Krebs solution at 37°C, and stimulated by an electrical field. 1H-[1,2,4]oxadiazolo-[4,3- a]quinoxalin-1-one (ODQ), a selective inhibitor of guanylyl cyclase, antagonized the off response, shortened its latency, and blocked the first phase of LES relaxation. ODQ also antagonized LES relaxation by exogenous nitric oxide (NO) but not relaxations by vasoactive intestinal polypeptide (VIP). Part of the nerve-induced LES relaxation and the off response appear to be mediated by the second messenger cGMP. These studies indicate that VIP-induced LES relaxation is not mediated by cGMP and therefore do not support the hypothesis that VIP produces LES relaxation by causing the generation of NO.

Action of prostaglandin synthetase inhibitors on rostral hypothalamic neurones: thermoregulation and biogenic amines

1976 ◽  
Vol 54 (2) ◽  
pp. 161-166 ◽  
Author(s):  
Ralph M. Jell ◽  
Paul Sweatman
Keyword(s):  
Biogenic Amines ◽  
Neuronal Excitability ◽  
Prostaglandin Synthesis ◽  
Prostaglandin Synthetase ◽  
Depressant Action ◽  
Rostral Hypothalamus ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Induced Changes

Sensitivity of neurones in the rostral hypothalamus of methoxyflurane anesthetized cats to the prostaglandin synthetase inhibitors (PGSIs), salicylate and fenoprofen, has been examined using the technique of microiontophoresis. Results were compared with sensitivity to prostaglandin (PG) E1 and no noradrenaline (NA) and 5-hydroxytryptamine (5HT). Simultaneous applications of PGSIs and NA or 5HT were made to investigate the role of PG in monoamine induced changes in neuronal excitability. PGSIs did not excite these cells, but depressions were common, particularly with fenoprofen. PGE1 did not reverse the depressions. NA and 5HT responses were generally unaffected by simultaneous PGSI application and responsiveness to PGSIs was found to be unrelated to amine sensitivity.The results support the conclusion that PGSIs have a depressant action on neurones in this region, which may not be related to inhibition of prostaglandin synthesis, and that the actions of microiontophoretically applied NA and 5HT are not dependent upon PG.

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