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1.
The addition of prostaglandin (PG) D 2 contracted helical strips of dog cerebral, coronary, renal and femoral arteries; the contraction was greatest in cerebral arteries. The contractile response of cerebral arteries was potentiated by aspirin and attenuated by polyphloretin phosphate. In the arterial strips contracted with PGF 2α, PGD 2 elicited a concetration-related relaxation; the relaxation was greatest in mesenteric arteries. In mesenteric arterial strips contracted with norepinephrine, a lesser degree of relaxation was induced, and in the K +-contracted arteries, only a contraction was induced. Treatment with PGD 2 attenuated the contractile responses of cerebral and mesentric arteries to PGF 2α or PGE 2; this inhibitory effect was approximately 10 times greater in mesenteric arteries. However, the response to serotonin (for cerebral arteries) or norepinephrine (for mesenteric) was unaffected. It may be concluded that the heterogeneity of response to PGD 2 of a variety of dog arteries is due to different contributions of vasoconstrictor and vasodilator mechanisms. PGD 2 appears top share the mechanism underlying arterial contraction with PGF 2α and PGE 2, and interferes with the effect of these PG's possibly on receptor sites. 相似文献
2.
The effects of prostacyclin (PGI 2) and its stable metabolite 6-oxo-PGF 1α on various bioassay tissues are compared with those of PGE 2 and PGF 2α, using the cascade superfusion method. On vascular smooth muscle, PGI 2 caused relaxation of all tissues tested except the rabbit aorta. PGE 2 relaxed rabbit coeliac and mesenteric artery but contracted bovine coronary artery and had no effect on rabbit aorta. 6-oxo-PGF 1α was ineffective at the concentrations tested.On gastro-intestinal smooth muscle, PGI 2 contracted strips of rat and hamster stomach and the chick rectum. It was less potent than PGE 2 or PGF 2α. None of these substances contracted that cat terminal ileum. 6-oxo-PGF 1α was inactive on these tissues at the doses tested.PGI 2 was less active than PGE 2 or PGF 2α in contracting guinea-pig trachea and rat uterus; 6-oxo-PGF 1α was active only on the rat uterus. Thus, PGI 2 can be distinguished from the other stable prostaglandins using the cascade method of superfusion. 相似文献
3.
Effects of prostaglandins (PGs) E 1, E 2, F 2α and I 2 in a wide range of concentration were examined in mesenteric and cerebral arteries isolated from mature baboons. PGs E 1, E 2 and F 2α at low concentrations (10 −10 to 10 −7 M) elicited relaxation in helically cut strips of cerebral arteries precontracted with phenylephrine. In contrast, the PGs did not cause relaxation in the mesentric artery. PGI 2 (10 −9 to 10 −6 M) produced marked relaxation in both arteries. The EC 25 for PGI 2 in the mesenteric artery was significantly lower than that in the cerebral artery. During baseline conditions, cerebral arteries contracted in response to high concentrations (greater than 10 −7 M) of PGs E 1, E 2 and F 2α. In mesentric arteries, a large contraction was induced by PGs F 2α and E 2 but not by PGE 1. Arachidonic acid (10 −6 M) produced an aspirin-inhibitable relaxation in both arteries to a similar extent, so that the vasodilator PG(s) formed in the two different arterial walls appear to exert a similar relaxant action. Thus, the baboon mesenteric artery was more sensitive to PGI 2 for the relaxant effect than was the cerebral artery, while PGs F 2α, E 1 and E 2 caused only a contraction in the mesenteric artery but both relaxation and contraction in the cerebral artery. 相似文献
4.
Prostacyclin (PGI 2) produced a biphasic response in canine isolated basilar arteries. In low doses (1 × 10 ?8M?1 × 10 ?7M) PGI 2 caused a slight but consistent relaxation of resting muscle tone. In low concentrations (1 × 10 ?8M?1 × 10 ?6M) PGI 2 antagonized muscle contractions caused by serotonin or prostaglandin (PG) F 2α. This relaxant effect with low doses of PGI 2 on the isolated cerebral artery contrasts with findings obtained with other PGs and supports the hypothesis that PGI 2 is a mediator of vasodilatation. However, in 1 × 10 ?5M concentrations PGI 2 contracted the arterial muscle and did not antagonize contractions induced by serotonin or PGF 2α. 相似文献
5.
Prostaglandins (PG)I 2, PGE 2 and 6-keto PGF 1α were infused directly into the gastric arterial supply at 10 −9, 10 −8 and 10 −7 g/kg/min during an intra-gastric artery pentagastrin infusion in anesthetized dogs. 6-keto PGF 1α was also infused at 10 −6 g/kg/min. Gastric arterial blood flow was measured continuously with a non-cannulating electromagnetic flow probe and gastric acid collected directly from the stomach. PGI 2 and PGE 2 produced similar dose-dependent increases in blood flow with an increase of more than four-fold at the highest dose. Both PGs inhibited acid output over this dose range with PGE 2 having 10 times the potency of PGI 2. 6-keto PGF 1α was at least 1000 times less active than PGI 2 or PGE 2 at increasing blood flow and failed to inhibit acid output even at 10 −6 g/kg/min. 相似文献
6.
Specimensfrom the ascending branch of the human uterine artery were obtained from 35 nonpregnant fertile women undergoing hysterectomy, The specimens were cut either longitudinally or helically and mounted in organ chambers for isometric recording of the contractile activity. Spontaneous phasis activity occured in 30% of the specimens.Both PGE 2 and PGF 2α caused an increase in basal tonus of the strips while PGI 2 relaxed spontaneously active as well as PG- and norepinephrine (NE)-stimulated preparations. PGI 2 had no effect on nonactive specimens. NE and transmural nerve stimulation (TNS) induced contractile activity that could be blocked by phenoxybenzamine. PGI 2 counteracted the NE-induced response but not that of TNS. It is concluded that PGI 2, which is synthesized both within the vessel wall and the myometrium, has a potent relaxing effect on uterine arteries and that the compound may balance the effect of vasocontricting substances. 相似文献
7.
The in vivo metabolism of 6-keto PGF 1α was investigated in rats. Following continuous intravenous infusion for 14 days the urinary metabolites were isolated and identified. A substantial amount of unchanged 6-keto PGF 1α was recovered in the urine. The metabolic pattern very closely resembles that of PGI 2 in rats. Metabolites were found which represented 15-dehydrogenation, β-oxidation, ω and ω-1-hydroxylation and oxidation.Previous work showed that 6-keto PGF 1α is very poorly oxidized by 15-PGDH. We administered 15-[H 3]-PGI 2 and 15-[H 3]-6-keto PGF 1α to rats and measured urinary tritiated water as an index for in vivo 15-PGDH activity. The results showed that PGI 2 and 6-keto PGF 1α were both oxidized to the 15-keto product, although the rate of oxidation of PGI 2 was greater than that of 6-keto PGF 1α. We concluded that the administered PGI 2 was oxidized by 15-PGDH before hydrolysis to 6-keto PGF 1α. A portion of the dose is probably hydrolyzed before 15-dehydrogenation. 相似文献
8.
The relationship between renin secretion and PGI 2 production, in response to intrarenal infusion of norepinephrine, was examined in the isolated perfused rat kidney. Infusion of norepinephrine in a dose which caused substantial vasoconstriction (100 ng/min), markedly increased urinary excretion of 6-keto PGF 1α, the stable derivative of PGI 2, without significantly altering renin secretion measured in the effluent perfusate. No change in urinary 6-keto PGF 1α occurred when vasoconstriction was prevented by infusing the alpha-adrenoceptor blocking drug phenoxybenzamine (2 × 10 3 ng/min) alongside norepinephrine 100 ng/min). However, under these conditions there was marked stimulation of renin secretion which, as has been demonstrated previously, is mediated by a beta-adrenoceptor. There were significant increase in urine flow rates during both vasoconstrictor and non-vasoconstrictor infusions. These findings clearly indicate that in the rat kidney prostacyclin production and renin release in response to norepinephrine are dissociated. 相似文献
9.
The thromboxane receptor antagonist EP 092 inhibits the acute pulmonary vascular response to
endotoxin in the anaesthetized, closed-chest sheep. The increase in the TXB 2 level in arterial blood was not suppressed by EP 092. Intravenous infusion of the thromboxane mimetic 11,9-epoxymethano PGH 2, but not PGF 2α, raises pulmonary artery pressure and lowers arterial pO 2 similar to the endotoxin. Isolated strips of lobar pulmonary veins but not lobar arteries are contracted by low concentrations of 11,9-epoxymethano PGH 2 - the effects are potently inhibited by EP 092. 相似文献
10.
Summary The current study was undertaken to assess species and regional variations in the relaxation of vascular smooth muscle in response to potassium and in the ouabain sensitivity of this relaxation. The effect of species variation was investigated through the use of tail arteries from rats, dogs, cats, monkeys, and pigs; the effect of regional variation was studied in tail, middle cerebral, femoral, and posterior coronary arteries from baboons. Helical strips from all of these vessels were made to contract with norepinephrine or serotonin in a potassium-free solution. The vessels relaxed when potassium was added back to the solution. Strips of tail artery from rats, dogs, and monkeys showed greater relaxation in response to potassium than did strips from pigs and cats. Helical strips from tail, cerebral, and coronary arteries of the baboon relaxed to a greater degree in response to potassium than did strips from the femoral artery. Ouabain produced a concentration-dependent decrease in the magnitude of potassium relaxation in all vessel types. Half-maximal inhibition occurred at approximately 10 –8 to 10 –7 M in all arterial strips except those obtained from rat tail artery (5×10 –5 M). The inhibition of potassium relaxation by ouabain was fully reversed by 30 min exposure to a ouabain-free solution in only the rat tail artery strips. A component of potassium-induced relaxation in tail artery strips from monkeys and baboons was not inhibited by ouabain. The results show that the magnitude of response, potassium and ouabain sensitivity, and recovery from ouabain treatment of potassium relaxation are species related. The regional bed from which the vascular smooth muscle is derived also determines the magnitude and potassium sensitivity of the relaxation. These parameters of potassium-dependent relaxation may reflect corresponding differences in the electrogenic pumping of sodium and potassium among various animal species and various regional vascular beds.Abbreviations
ATPase
adenosine triphosphatase
-
PSS
physiological salt solution
-
C
contractile magnitude from baseline in milligrams
-
R
relaxation measured as residual force above baseline in milligrams
-
SEM
standard error of the mean
These studies were supported by NHLBI grant HL-18575Dr. Webb was a Post-doctoral Research Fellow of the Michigan Heart Association during this investigation 相似文献
11.
Intact rings and homogenates of aorta from spontaneously hypertensive rats (SHR) contain enhanced capacity over normal rats (NR) to convert arachidonic acid into PGI 2. The PGI 2 synthetic system in SHR is stimulated to a greater extent than NR by norepinephrine. Indomethacin blocks this stimulation. PGE 2 and PGF 2α were detected in much smaller amounts in homogenates (undetected in rings) but their formation was not enhanced by the hypertensive tissue. The identity of PGI 2 was based on 1) direct pharmacological assay on the rat blood pressure. In this system identical vasodepressor responses to PGI 2 are observed after intracarotid and intrajugular administration 2) indirectly as 6-keto PGF 1α isolated after incubation of aortic homogenates with tritiated arachidonic acid and 3) indirectly by GC-MS assay of PGE 2, PGF 2α and 6-keto PGF 1α formed during incubation of aortic homogenates with excess unlabeled arachidonic acid. These results provide additional support to our recent hypothesis that PGI 2, of aortic origin, might actively participate in the regulation of systemic blood pressure. Its enhanced formation by intact hypertensive vascular tissue reflects an increase in the number of enzyme molecules immediately available to the substrate. This could probably be an adaptive response to the elevated levels of catecholamines in the circulation. 相似文献
12.
Prostacyclin (PGI 2) dose-dependently increases the adenosine 3′,5′-cyclic monophosphate (cyclic AMP) levels in canine femoral, carotid, and canine and bovine coronary arteries. The prostacyclin-stimulation is enhanced by phosphodiesterase inhibitors, and is readily measurable after 60 sec incubation. The prostaglandin endoperoxide PGH 2, but not PGH 1, also elevates cAMP levels in femoral arteries. Inhibition of arterial prostacyclin synthetase with 28 μM 9,11-azoprosta-5,13-dienoic acid (azo analog I) blocks the PGH 2-stimulation of cAMP accumulation. Azo analog I does not attenuate a direct PGI 2 stimulation, indicating that the PGH 2 dependent elevation of cAMP is due to conversion of PGH 2 to PGI 2 by the artery. PGI 2 and PGE 1 increase cyclic AMP levels and relax dog femoral and bovine coronary arteries, while PGE 2, which actually contracts bovine coronary arteries, has no effect on arterial cyclic AMP levels. The significance of the PGI 2-stimulation of arterial cyclic AMP is not known, but it is probably related to relaxation of arterial strips. 相似文献
13.
Endothelial cells synthesize and release nitric oxide (NO) and prostacyclin (PGI 2) which are involved in the regulation o f vascular tone and blood pressure. Our objective was to evaluate the effects of inhibiting NO synthesis on vascular prostaglandin (PG) and cyclic nucleotide production, as well as the pressor response to norepinephrine (NE). Isolated mesenteric arterial beds were perfused with Krebs-Henseleit solution containing 100 μM N G-monomethyl-L-arginine (L-NMMA), 100 μM L-arginine (LA), or vehicle. After a 30 min equilibration 0.1, 0.5, 1, or 5 μM NE was infused into the superior mesenteric artery and the perfusion pressure was monitored. The basal perfusion pressure did not differ significantly between groups. The pressure-response curve was shifted to the right in the L-NMMA group vs. the LA and control groups. Perfusion was similarly performed with a Krebs-Henseleit solution containing 100 μM L-NMMA, LA, D-arginine, or vehicle. Perfusates were collected before and after NE infusion for the measurement of PGE 2, 6-keto-PGF 1α, TxB 2, cAMP, and cGMP. In the L-NMMA group the release of PGE 2 and 6-keto-PGF1α was decreased, and the release of cGMP was prevented. Production of cAMP did not differ between the four groups before NE infusion, and NE increased cAMP release in the L-NMMA group and controls. The results indicate that inhibition of NO synthesis by L-NMMA enhanced the pressor response to NE, possibly mediated by the decreased cGMP and PGI 2 production in resistance vessels. 相似文献
14.
In patients with peripheral vascular disease and in healthy rabbits, infusion of PGI 2 but not of 6-keto PGF 1α induced a rise in blood glucose level and a pathological deviation in glucose tolerance test. In experiments
, the increased concentrations of glucose produced dose-dependent inhibition of PGI 2 release from isolated rat aortic rings. The link between PGI 2 and carbohydrate metabolism is discussed. 相似文献
15.
Small strips from the circular and longitudinal muscle layers of the ampullary-isthmic portion of the human oviduct were mounted in organ chambers for recording of their spontaneous contractility. Concentrations in the order of 1–300 ng/ml of PGI 2 were tested and compared with similar concentrations of PGE 2 and PGF 2α. It was found that PGI 2 contracted the longitudinal muscle layer in the same manner as did PGE 2. The spontaneous activity of the circular layer was markedly suppressed by PGE 2 but only moderately inhibited by PGI 2 even at high concentrations. 相似文献
16.
The spontaneous output of prostaglandin (PG) I 2 from the perfused mesenteric arterial bed in vitro was significantly higher in hypertensive rats than in normotensive rats. Sympathetic nerve stimulation (at 10Hz) of the mesenteric arterial bed from normotensive rats caused a rapid and short-lived (< 4 min) two-fold increase in PGI 2 output and a smaller increase in PGE 2 output. Sympathetic nerve stimulation (at 10Hz) of the mesenteric arterial bed from hypertensive rats failed to increase PGI 2 and PGE 2 output. It is not possible to conclude whether this lack of response is a cause or a result of hypertension. Surprisingly, norepinephrine administration stimulated PGI 2 and PGE 2 release from the mesenteric arterial bed of both normotensive and hypertensive rats. Obviously, differences exist in the responsiveness of rat mesenteric arteries to endogenous and exogenous norepinephrine concerning PG release between the normotensive and hypertensive states. 相似文献
17.
Histamine caused a triphasic response of human pulmonary artery strips in vitro, consisting of a small initial contraction followed by pronounced relaxation preceding a second contractile response. These characteristics were not seen with other contractile stimuli including 5-hdyroxytryptamine, leukotriene D 4, and KC1. The relaxant component of this response was ablated by removal of endothelium from the vascular strips or by pretreatment of the tissues with 1μM indomethacin. Measurement of the PGI 2 degradation product 6-keto-PGF 1α in supernatants from histamine-challenged tissues confirmed the synthesis of PGI 2. Supernatants from unstimulated or leukotriene-challenged tissues contained no detectable amounts of 6-keto-PGF 1α. The histamine H 1 antagonist diphenhydramine inhibited both the contractile and relaxant responses to histamine whereas the H 2 antagonist cimetidine affected neither component. The released PGI 2 significantly altered the dose-respons curve to histamine without inhibiting the maximal contractile responses. We conclude that histamine induces PGI 2 formation from pulmonary arterial endothelium via an H 1 receptor. 相似文献
18.
Uridine 5′-triphosphate (UTP) has an important role as an extracellular signaling molecule that regulates inflammation, angiogenesis, and vascular tone. While chronic hypertension has been shown to promote alterations in arterial vascular tone regulation, carotid artery responses to UTP under hypertensive conditions have remained unclear. The present study investigated carotid artery responses to UTP in spontaneously hypertensive rats (SHR) and control Wistar Kyoto rats (WKY). Accordingly, our results found that although UTP promotes concentration-dependent relaxation in isolated carotid artery segments from both SHR and WKY after pretreatment with phenylephrine, SHR exhibited significantly lower arterial relaxation responses compared with WKY. Moreover, UTP-induced relaxation was substantially reduced by endothelial denudation and by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine in both SHR and WKY. The difference in UTP-induced relaxation between both groups was abolished by the selective P2Y2 receptor antagonist AR-C118925XX and the cyclooxygenase (COX) inhibitor indomethacin but not by the thromboxane-prostanoid receptor antagonist SQ29548. Furthermore, we detected the release of PGE2, PGF2α, and PGI2 in the carotid arteries of SHR and WKY, both at baseline and in response to UTP. UTP administration also increased TXA2 levels in WKY but not SHR. Overall, our results suggest that UTP-induced relaxation in carotid arteries is impaired in SHR perhaps due to impaired P2Y2 receptor signaling, reductions in endothelial NO, and increases in the levels of COX-derived vasoconstrictor prostanoids. 相似文献
19.
Experiments with anesthetized cats were done to study possible roles of different prostaglandins (PGs) in modulating sympathetic neuroeffector transmission. We recorded contractions of the nictitating membrane (n.m.), blood flow in the carotid artery, heart rate and blood pressure, both under control conditions and while stimulating the cut cervical sympathetic nerve. Intra-carotid arterial injection (i.a.) of PGD 2 depressed sympathetic transmission to the n.m. without depressing the effects of exogenous norepinephrine (NE). In contrast, PGE 2 enhanced the effects of nerve transmission or exogenous NE on the stimulated n.m. PGI 2 had similar but shorter effects to PGE 2. PGF 2α or a stable PGH 2 analog, contracted the n.m. smooth muscle with no detected effect on nerve transmission. Carotid blood flow was increased by PGD 2, PGE 2 and PGI 2. PGD 2 and PGI 2 caused bradycardia that could be blocked by atropine. This ability of PGD 2 to modulate autonomic nerve activity is of particular interest because of recent reports that nerve tissue synthesizes PGD 2. 相似文献
20.
While no significant effects on the in vitro production of PGF 2α by homogenates of rat estrous uteri were observed in the presence of 10 −3 and 10 −6M Cu 2+, the presence of Cu 2+ at 10 −4 and 10 −5M was found to stimulate production with maximal synthesis of PGF 2α occurring with 10 −4M Cu 2+. By contrast, the synthesis of PGE 2 and PGI 2 (determined as 6-keto PGF 1α) were unaffected at all of the different Cu 2+ concentrations used. When indomethacin and salicylic acid were tested for their effects on the Cu 2+-mediated levels of PG synthesis by the homogenates, indomethacin (at 20μM) was found to cause similar pronounced decreases in PGF 2α, PGE 2 and 6-keto PGF 1α whereas salicylic acid (400μM) showed preference towards suppressing PGE2 and 6-keto PGF 1α production. 相似文献
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