6-ketoprostaglandin-f1-alpha and Cerebrovascular-Disorders

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Circulation; Cerebrovascular Disorders; Coronary Disease; Drugs, Chinese Herbal; Humans; Medicine, Chinese Traditional; Syndrome; Thrombosis; Thromboxane B2

To examine the antiplatelet effect of a novel pyrazolopyridine derivative (KC-764) in geriatric patients with ischemic stroke.. Randomized clinical trial of three graded dose levels.. A geriatric clinic attached to a nursing home.. Fifteen patients with a history of cerebral infarction with a mean age of 75 +/- 5 years (range, 65-83). Patients were divided into three groups and administered 10, 20, or 40 mg/day KC-764 for 8 weeks.. Platelet aggregation induced by arachidonate, ADP, collagen and platelet-activating factor. Plasma or serum levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha.. Platelet aggregation was inhibited by KC-764 administration and returned to the control level after discontinuation. Although plasma thromboxane B2 levels were markedly decreased, plasma 6-ketoprostaglandin F1 alpha was not affected. However, the dose of 10 mg/day was not sufficient to maintain an effective plasma level of KC-764. There were no side effects or changes in laboratory findings.. We confirmed that KC-764 at a dose of 20 to 40 mg/day is an effective antiplatelet agent and a good candidate for a trial to see if it is feasible for long-term use for the prevention of ischemic stroke in high-risk patients.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Aged; Aged, 80 and over; Brain Ischemia; Bridged Bicyclo Compounds; Cerebrovascular Disorders; Chromatography, High Pressure Liquid; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Humans; Nicotinic Acids; Platelet Aggregation Inhibitors; Thromboxane B2

In order to delve into the mechanism governing the treatment of apoplexy by acupuncture at yangming channel points as main points, we observed the changes in the endothelin (ET) level in plasma, TXB2 and 6-Keto-PGF1 alpha levels in urine in convalescent apoplexy patients during acupuncture treatment. The results showed that the ET level in plasma in convalescent apoplexy patients was significantly higher than that in healthy subjects (P < 0.05), and the ET level in plasma in patients was decreased after one course of acupuncture treatment. It was found that before treatment the TXB2 level in urine in apoplexy patients was significantly higher than in healthy subjects, and the 6-Keto-PGF1 alpha level in urine in the patients was significantly lower than that in healthy subjects, with an increased ratio of TXB2 to 6-Keto-PGF1 alpha. After acupuncture treatment, the TXB2 level in urine was lowered with a decrease in the ratio of TXB2 to 6-Keto-PGF1 alpha. All this indicated that one of the mechanisms governing acupuncture treatment of apoplexy acupuncture at yangming channel points as main points was that acupuncture could produce therapeutic effects by adjusting the imbalance of important vaso-active substances, ET, TXA2, and PGI2.

Topics: 6-Ketoprostaglandin F1 alpha; Acupuncture Therapy; Adult; Aged; Cerebrovascular Disorders; Convalescence; Endothelins; Female; Humans; Male; Middle Aged; Thromboxane B2

Angiotensin-converting enzyme (ACE) inhibitors can improve cardiac function independent of their blood pressure (BP)-lowering actions. We investigated the effect of chronic subantihypertensive ACE inhibitor treatment on functional and biochemical cardiac parameters in stroke-prone spontaneously hypertensive rats (SHRSP). Animals were treated in utero and subsequently to age 20 weeks with the ACE inhibitor perindopril (0.01 mg/kg/day). The contribution of endogenous bradykinin (BK) potentiation to the actions of the ACE inhibitor was assessed by cotreatment with the BK beta 2-receptor antagonist Hoe 140 (500 micrograms/kg/day subcutaneously, s.c.) from age 6 to 20 weeks and by measurement of myocardial prostacyclin and cyclic GMP concentrations. Chronic low-dose perindopril treatment had no effect on development of hypertension and left ventricular hypertrophy (LVH), but perindopril improved cardiac function, as demonstrated by increased LV pressure (LVP) (19.4%) and LVdp/dtmax (27.8%) but no change in heart rate (HR). The activities of lactate dehydrogenase (LDH) and creatine kinase (CK) as well as lactate concentrations in the coronary venous effluent were reduced by 39.3, 50, and 60.6%, respectively. Myocardial tissue concentrations of glycogen and the energy-rich phosphates ATP and CK were increased by 16.3, 33.1, and 28.2%, respectively. All ACE inhibitor-induced effects on cardiac function and metabolism were abolished by concomitant chronic BK receptor blockade. Cardiac prostacyclin concentrations were threefold elevated in perindopril-treated animals whereas cardiac cyclic GMP concentration remained unchanged as compared with that of controls. Our data demonstrate that chronic low-dose ACE inhibitor treatment can improve cardiac function and metabolism by potentiating endogenous BK.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Bradykinin; Cerebrovascular Disorders; Coronary Circulation; Creatine Kinase; Cyclic GMP; Disease Models, Animal; Glycogen; Heart; Heart Rate; Hypertension; Hypertrophy, Left Ventricular; Indoles; L-Lactate Dehydrogenase; Myocardium; Perindopril; Rats; Rats, Inbred SHR

We investigated the effect of two oral (p.o.) doses of cicletanine (5 and 30 mg/kg/day) for 4 weeks on urinary excretion (UKE), renal concentration (RKC) of kallikrein, and prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha urinary excretion of stroke-prone (SP) spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) rats submitted to a high sodium intake (1%). Both doses of cicletanine induced a significant antihypertensive effect in treated SHR as compared with hypertensive untreated controls (HC). After 4-week treatment, a significant difference in mortality was observed between normotensive controls (NC) (0%) and HC (84%). Both doses of cicletanine reduced the mortality of hypertensive animals (8% SHR with 5 mg and 24% SHR with 30 mg vs. 84% in HC). Whereas UKE and RKC were decreased in HC during the progression of untreated hypertension from week 1 to week 4, both doses of cicletanine administration significantly prevented this decrease. Consistently with maintenance of UKE during the course of hypertension, the level of tissue kallikrein was higher in hypertensive cicletanine-treated than in untreated SHR. This increased RKC was associated with a significantly higher rate of kallikrein biosynthesis. The increased level of the urinary excretion and tissue concentration of PGE2 and 6-keto-PGF1 alpha in cicletanine-treated SHR as compared with untreated animals was also of interest. This protective effect on PG excretion correlated with that on kallikrein excretion. The results confirm the efficiency of cicletatine as an antihypertensive treatment. The antihypertensive action includes protective effects on potential vasodepressor kallikrein-kinin and prostaglandin systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Amino Acid Sequence; Animals; Antihypertensive Agents; Blood Pressure; Cerebrovascular Disorders; Dinoprostone; Hypertension; Kallikrein-Kinin System; Kallikreins; Kidney; Kinins; Male; Molecular Sequence Data; Phospholipases A; Prostaglandins; Pyridines; Rats; Rats, Inbred SHR; Rats, Inbred WKY

By means of the radioimmunologic method changes of concentration of 6-keto-prostaglandin F1 alpha (PGF1 alpha)--the stable metabolite of prostacyclin in the rat brain have been evaluated during 5-min clinical death and up to 2 hrs after resuscitation. Ischemia did not produce significant changes of 6-keto-PGF1 alpha concentration in the brain. In the early postresuscitation period the concentration of 6-keto-PGF1 in the and 7-fold control values. Later the concentration of 6-keto-PGF1 alpha in the brain decreased reaching in 30 min a 3-fold the control level, and in 60 and 120 min after resuscitation control values. The reasons of unsuccessful therapy of ischemic stroke with prostacyclin are discussed.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain Chemistry; Brain Ischemia; Cerebrovascular Disorders; Epoprostenol; Female; Radioimmunoassay; Rats; Rats, Wistar; Resuscitation

The purpose of this study was to compare the effects of low-to-high doses of aspirin on platelet aggregability determined by different methods and on the metabolism of thromboxane A2 and prostacyclin.. We administered increasing doses (40, 320, and 1,280 mg/day) of aspirin to 19 poststroke patients and studied the differences in 1) the changes in platelet aggregability depending on the methods of evaluation and 2) the concentrations of prostaglandin metabolites in the blood and urine.. Aggregation of platelet-rich plasma induced by a strong stimulus (10 microM ADP) was significantly reduced after 40 mg/day aspirin (p less than 0.005), and this reduction was similar to that after higher aspirin doses. In contrast, aggregation of platelet-rich plasma induced by weaker stimuli (1 and 5 microM ADP) decreased less significantly after 40 mg/day aspirin compared with that after higher aspirin doses. The serum thromboxane B2 generated after ex vivo incubation was reduced significantly (by 85%) after 40 mg/day aspirin and decreased further after 320 mg/day (by 96%) and 1,280 mg/day (by greater than 99%) of aspirin. The urinary 11-dehydro-thromboxane B2 concentration decreased less significantly after 40 mg/day aspirin (by 42%) compared with that after 320 mg/day (by 78%) and 1,280 mg/day (by 91%) aspirin doses. The urinary concentration of 2,3-dinor-6-keto-prostaglandin F1 alpha did not decrease after 40 mg/day aspirin but decreased significantly after higher doses of aspirin.. These findings suggest that different doses of aspirin may be necessary to prevent thrombogenesis induced by different triggers of different strengths and that 40 mg/day aspirin is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aspirin; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Epoprostenol; Female; Humans; Male; Middle Aged; Platelet Aggregation; Thromboxane A2; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Aged, 80 and over; Cerebrovascular Disorders; Dinoprostone; Female; Heart Diseases; Humans; Male; Middle Aged; Radioimmunoassay; SRS-A; Thromboxane B2

The relation of brain eicosanoids to progression of cerebral edema was studied in stroke-resistant spontaneously hypertensive rats subjected to incomplete global brain ischemia induced by bilateral occlusion of the common carotid arteries. Thromboxane B2 and 6-keto prostaglandin F1 alpha levels were significantly elevated 5 minutes after reperfusion but returned to control levels by 30 minutes. In contrast, leukotriene C4 levels increased 2 hours after bilateral common carotid artery occlusion and peaked 30 minutes after reperfusion, with higher levels persisting until 60 minutes after reperfusion. Cerebral ischemia was accompanied by cerebral edema early after reperfusion. The edema correlated with increased leukotriene C4 levels. That the increased brain water content was causally related to an increase in leukotriene C4 was supported by results obtained following administration of the 5-lipoxygenase inhibitors ONO-LP-016 and AA-861. Both inhibitors suppressed the increased leukotriene C4 and brain water contents after reperfusion. Our results indicate that leukotriene C4 is closely associated with an induction of ischemic cerebral edema.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Benzoquinones; Body Water; Brain; Brain Edema; Cerebrovascular Circulation; Cerebrovascular Disorders; Disease Susceptibility; Eicosanoic Acids; Hypertension; Male; Quinones; Rats; Rats, Inbred SHR; SRS-A; Thromboxane B2

A thrombo-embolic stroke model was produced by the internal carotid artery (ICA) infusion of arachidonic acid (AA). The differences in responses to AA ICA infusion were investigated in stroke-resistant spontaneously hypertensive rats (SHRSR) and Wistar-Kyoto (WKY) rats. The SHRSR showed a higher mortality, more severe brain oedema and brain metabolic impairment, more prominent elevation of TXB2 and 6-keto-PGF1 alpha. Electron microscopic observation revealed more severe endothelial damage, mitochondrial swelling and perivascular oedema and earlier thrombus formation in SHRSR than in WKY rats.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Brain; Brain Ischemia; Cerebrovascular Disorders; Hypertension; Male; Microscopy, Electron, Scanning; Rats; Rats, Inbred Strains; Thromboxane B2