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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin (5 nmol/kg, i.v.) caused a transient hypotension followed by a lasting hypertension in rats. However, an abrupt fall in the blood pressure was observed in most rats 6 to 30 min after the injection of endothelin and sudden death followed with lethality noted over 60 min. An abnormal electrocardiogram (ECG) (ventricular arrhythmias) was observed in rats injected with endothelin. Endothelin (i.v.) also caused sudden death in mice. Pretreatment (5 or 60 min) with specific PAF antagonists, CV-6209 (0.1-3 mg/kg, i.v.) and WEB 2086 (30 mg/kg, p.o.), and a calcium channel blocker, diltiazem (60 mg/kg, p.o.) prevented death and attenuated the ECG changes induced by endothelin, but CV-6209 did not prevent the blood pressure changes induced by endothelin. CV-6209 (0.5-3 mg/kg, i.v.), WEB 2086, diltiazem and dexamethasone (5 mg/kg, i.v.) protected mice against the death induced by endothelin. On the other hand, aspirin (cyclooxygenase inhibitor, 100 mg/kg, p.o.) did not protect mice from the death. Thus, endothelin is a highly toxic peptide with cardiotoxic effects, and PAF may be involved in the pathogenesis of the sudden death.
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PMID:Endothelin-induced sudden death and the possible involvement of platelet activating factor (PAF). 268 21

A 43-year-old male with "pure" progressive autonomic failure ("pure" PAF) was admitted to our hospital in June 1988, with a chief complaint of recent syncopal attacks while standing. Since the age of 35. He has noticed dyshidrosis on his left side. The family history was negative. Neurological examination showed dyshidrosis on his left side and profound orthostatic hypertension. No other neurological abnormalities were noted. Autonomic function tests revealed sympathetic and parasympathetic dysfunction as follows: Adrenaline administered subcutaneously gave a hyperactive pressor response from 136/82 mmHg to 190/116 mmHg with the pulse increasing from 54 to 150 beats per min. Hidrosis was observed on the right side of the body in response to heat. However, it was observed over the whole body in response to pilocarpine. In the studies of pupillary response to instillation of 1.25% epinephrine, both pupils were unchanged in diameter; after 5.0% tyramine, both pupils were dilated from 3.5 mm to 5.0; and after 2.5% methacholine, the right and left pupils, each originally 4.5mm were constricted to 3.5 mm and 4.0 mm, respectively. From the above data, this case was diagnosed as "pure" PAF. 133Xe inhalation method. The mean regional CBF (F1) values were reduced from 91 to 53 ml/100 g brain/min by postural change from supine to sitting position, associated with a decrease in mean arterial blood pressure (MABP) of 28 mmHg (from 103 to 75 mmHg). This result shows the impairment of CBF autoregulation in this patient. This case adds further evidence to the hypothesis that the autonomic nervous system plays a role in CBF autoregulation.
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PMID:[A case of "pure" progressive autonomic failure with impairment of cerebral blood flow autoregulation]. 269 14

Cerebral ischemia and ischemia-reperfusion induced cerebral injury results in the accumulation of free fatty acids and diacylglycerols as a result of increased activity of phospholipases A and C. We have evaluated the incorporation of 14C arachidonic acid into the whole brain and synaptoneurosomes, the effect of cerebral ischemia on 14C incorporation, and the effect of a PAF antagonist (BN 52021) on cerebral blood flow, free fatty acids, diacylglycerols, and polyphosphoinositides. Peak incorporation of 14C arachidonic acid into the whole brain and synaptoneurosomal fractions occurred 30 minutes following intraventricular injection. Peak incorporation into cerebellar synaptoneurosomal fractions was at 60 minutes following intraventricular injection. Turnover in phospholipid pools was similar in the whole brain and synaptoneurosomes (PI greater than PC greater than PE). Considering phosphatidylinositol content in the gerbil brain, the specific activity of 14C arachidonic acid was 22 times greater in PI than PC. Five minutes of bilateral carotid artery ligation resulted in decreased phosphatidylinositol and polyphosphoinositols. Bilateral carotid artery ligation resulted in systemic arterial hypertension, complete forebrain ischemia (CBF less than 7 ml/100 gm/min) and a 20% to 50% reduction in midbrain CBF. Reperfusion resulted in cerebral reactive hyperemia and systemic hypotension. BN 52021 inhibited the maturation of ischemia-reperfusion induced cerebral injury. Cerebral blood flow was improved. Free fatty acids were decreased, suggesting inhibition of phospholipase A activity. Decreased DAG pools with increased PIP2 pools suggest a possible coinhibition of phospholipase C.
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PMID:Arachidonic acid metabolism and cerebral blood flow in the normal, ischemic, and reperfused gerbil brain. Inhibition of ischemia-reperfusion-induced cerebral injury by a platelet-activating factor antagonist (BN 52021). 277 4

The effect of PAF has been examined in anaesthetized guinea-pigs. Intravenous (i.v.) administration of PAF (10 ng kg-1) did not modify the respiratory response but decreased the arterial blood pressure. A high dose of PAF (200 ng kg-1) caused marked bronchoconstriction and concomitant hypertension. The cyclooxygenase inhibitors aspirin (5 mg kg-1) and indomethacin (5 mg kg-1) and the thromboxane A2 (TXA2) receptor antagonist BM-13.177 (1 mg kg-1) failed to inhibit the peak bronchoconstrictive response but significantly inhibited the prolonged response following peak response. These inhibitors also attenuated PAF-induced hypertension. On the other hand, the lipoxygenase inhibitors phenidone (10 mg kg-1) and NDGA (5 mg kg-1) and the leukotriene (LT) receptor antagonist FPL-55712 (2 mg kg-1) affected neither bronchoconstriction nor hypertension induced by PAF. However, when aspirin was given in combination with NDGA, phenidone or FPL-55712, the peak and the following prolonged bronchoconstriction were significantly inhibited. The suppression of PAF-induced hypertension by aspirin was not further inhibited by the combination of these inhibitors. These results indicate that in anaesthetized guinea-pigs PAF-induced bronchoconstriction is composed of a dual response, a direct action (peak response) and an indirect action (prolonged response). The latter may be produced by the generation of TXA2 and lipoxygenase products, while PAF-induced hypertension is indirectly mediated by the generation of TXA2.
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PMID:Pharmacological modulation of platelet activating factor (PAF)-induced bronchoconstriction and hypertension in anaesthetized guinea-pigs. 290 7

Systemic administration of platelet activating factor (PAF; acetyl glyceryl ether phosphorylcholine) reduces renal blood flow, but the mechanism responsible for that effect has not been defined. To address that problem, we determined the effects on renal blood flow of PAF administered directly into the renal artery in pentobarbital (30 mg/kg)-anesthetized dogs. Bolus injections of PAF (0.2-0.8 microgram) caused transient renal vasoconstriction, reducing renal blood flow by 20 to 60% without altering systemic blood pressure; lyso-PAF (1 microgram) had no effect. The effects of PAF on renal blood flow were not altered by alpha-adrenergic blockade (phentolamine, 3 mg/kg) or by angiotensin II receptor blockade ([Sar1,Ala8]angiotensin II, 6 micrograms/kg/min), but they were increased in magnitude and duration by meclofenamate (5 mg/kg), a cyclooxygenase inhibitor. Methysergide (3 mg/kg), a serotonin antagonist, slightly reduced PAF effects, but a specific blocker of vascular serotonin receptors did not. Renal venous plasma platelet density was not altered by infusion of PAF into the renal artery at a dose (1-2 micrograms/min) that caused a sustained 20% renal blood flow decrease. Alprazolam, a benzodiazepine that competitively inhibited PAF-induced aggregation in canine platelet-rich plasma, also inhibited the renal vasoconstrictor action of PAF (0.8 mg/min, into the renal artery) but did not alter renal vasoconstrictor effects of norepinephrine or angiotensin II.
Hypertension 1987 Mar
PMID:Platelet activating factor vasoconstriction of dog kidney. Inhibition by alprazolam. 381 22

Synthetic platelet-activating factor (PAF-acether) was shown to act as a shock inducer when a dose of 9 or 36 nmol . kg-1 was injected i.v. into dogs anesthetized with 30 mg . kg-1 i.v. sodium pentobarbitone. Nine nmol . kg-1 PAF-acether caused portal vein and pulmonary artery hypertension but only transiently; blood TXB2 and 6 keto PGF1 alpha levels rose; there was a lasting fall of 77% in systemic blood pressure, cardiac output fell by 86%, heart rate by 17%, plasma volume by 43%, and femoral artery blood flow by 66%, whereas the hematocrit rose by 33%. A dose of 36 nmol . kg-1 PAF-acether reduced coronary artery blood flow by 56%, diminished myocardial O2 consumption, raised O2 extraction and caused metabolic acidosis leading to death in 2 out of 7 animals. All these changes displayed the typical features of common acute circulatory collapse with distributive and hypovolemic etiologies, suggesting that PAF-acether might be an endogenous mediator in the early and late stages of shock.
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PMID:Acute circulatory collapse caused by platelet-activating factor (PAF-acether) in dogs. 668 72

1. Pretreatment with intravenous WEB-2086 (0.5 mg/kg; an antagonist of the actions of platelet activating factor; PAF) with or without indomethacin (2 mg/kg) failed to prevent or modify the fall in blood pressure following unclipping of the renal artery of anaesthetized two-kidney, one-clip hypertensive rats. 2. The same medications given to two other groups of rats 60 min after unclipping when the blood pressure had fallen to stable levels failed to reverse the fall. 3. Despite evidence that both prostanoids and PAF can be detected in increased amounts in renal venous blood after unclipping, they do not appear to mediate the reduction in blood pressure in this model of reversible hypertension.
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PMID:WEB-2086 and indomethacin do not modify blood pressure fall on unclipping hypertensive rats. 795 50

Thirty-seven men with angiography or ultrasound confirmed peripheral arterial occlusive disease were divided into two groups. Group 1 included 24 patients treated with one daily infusion of 10 g of phosphocreatine in 200 ml of solvent for 10 days. Group 2 included 13 patients who were given 0.9% NaCl in the same scheme. Groups were comparable in: duration of intermittent claudication, maximal walking distance, Ketle index, cholesterol, triglycerides, frequency of ischemic heart disease, hypertension, diabetes, smoking. Patients were examined 4 times: before starting, on second day, after treatment period, and 1 month after. Treadmill-test; ADP-, PAF-, 5-HT-induced platelet aggregation; D-dimer; PAI-1 activity; blood viscosity at high and low shear rate; hematocrit were performed. After treatment maximal walking distance significantly increased in patients of Group 1. Mechanisms of this effects include positive influence of phosphocreatine on platelet aggregation, blood rheology, coagulation and fibrinolytic systems.
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PMID:The effect of exogenous phosphocreatine on maximal walking distance, blood rheology, platelet aggregation, and fibrinolysis in patients with intermittent claudication. 807

Experiments were performed in pentobarbital-anesthetized rats, to study the mechanism of the acute pulmonary edema induced by Tityus serrulatus scorpion venom. In control rats injection of venom (50 micrograms/100 g, i.v.) induced arterial hypertension and lung edema (lung/body index or LBI equal to 1.01 +/- 0.09). In rats pretreated with heparin (100 IU/100 g 30 min previously) the venom induced similar hypertensive effects, but no edema was detected (LBI = 0.63 +/- 0.06, P > 0.05). Similarly, in rats pretreated with the PAF antagonist BN-52021 (0.5 mg/100 g, i.v., 30 min previously), the venom-induced hypertension was not modified but the acute pulmonary edema was prevented (LBI = 0.67 +/- 0.08, P > 0.05). It is concluded that PAF plays an important role on the genesis of pulmonary edema induced by scorpion venom in the rat. It is suggested that the inhibitory action of heparin could be related to a decrease in the vascular permeability in the lungs.
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PMID:Heparin or a PAF antagonist (BN-52021) prevents the acute pulmonary edema induced by Tityus serrulatus scorpion venom in the rat. 826 52

Accumulating evidence tends to demonstrate that inflammatory processes are responsible for neurological damage and sequelae in bacterial meningitis in children and infants. Massive liberation of bacterial cell wall components (Lipopolysaccharide, acid teichoic polymers) induce a cascade of reactions including the secretion of many cytokines (such as TNF alpha and IL-1 beta) and prostaglandins (such as PAF and PGE2) which in turn leads to the development of cerebral oedema, intracranial hypertension and cerebral blood flow reduction. Dexamethasone (DXM) is effective at the beginning of the inflammatory cascade and its utilisation in the meningitis experimental model in animals has shown significant reduction in the inflammatory response to bacterial meningitis. The first clinical studies using DXM as an adjunctive therapy to antibiotics have demonstrated its beneficial effect in terms of complications and long-term neurological sequelae in Haemophilus influenzae meningitis in children and infants. It seems that a similar effect can be obtained in meningococcal and pneumococcal meningitis. Little information is actually available concerning the use of DXM in penicillin-resistant pneumococcal meningitis. The rare reported cases of ceftriaxone failure with DXM as treatment of penicillin-resistant pneumococcal meningitis had a favorable outcome with the use of vancomycin.
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PMID:[Role of dexamethasone in the treatment of purulent meningitis in infants and in children]. 839 88


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