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

It is suggested that patients with the haemolytic-uraemic syndrome and related disorders (such as thrombotic thrombocytopenic purpura) lack a plasma factor which stimulates prostacyclin (P.G.I2) activity. Normal plasma would supply the missing factor and is a rational treatment for some life-threatening symptoms (thrombocytopenia, haemolytic anaemia, hypertension) of this syndrome.
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PMID:Haemolytic-uraemic syndrome: deficiency of plasma factor(s) regulating prostacyclin activity? 8 15

Prostaglandins (PG) are highly unsaturated, cyclic fatty acids with 20 carbon atoms which are biosynthesized from dihomo-gamma-linolenic, arachidonic and eicosapentaenoic acids. These fatty acids are either ingested or are biosynthesized from linoleic and linolenic acids, respectively. The PG-precursor fatty acids are liberated from membrane phospholipids by phospholipase A and are converted to prostaglandins by the multienzyme complex PG-synthetase. The activity of the PG-system is influenced by extracellular hormonal, neural and mechanical stimuli and by intracellular factors such as ion-concentration and activity of the enzymes adenyl- and guanylcyclase. Prostaglandins are tissue hormones or autacoids which act on their receptors near their site of synthesis and degradation. The prostaglandin family constitutes a group of more than 10 natural occurring compounds showing a variety of biological actions. In arteries and veins the different PG:s have vasodilating as well as vasoconstricting effects. In addition, they are involved in the regulation of vascular smooth muscle proliferation. Within the kidney PG:s have vascular and tubular actions. They antagonize the effect of ADH, mediate renin secretion and are involved in the control of electrolyte balance. In the regulation of platelet aggregation and platelet adhesion PG:s have opposite functions: Prostacyclin which is synthesized in the vascular wall antagonizes the aggregating action of Thromboxane A2 which is formed in the platelets. A defect or an imbalance in the production of PG:s in the vascular wall, in platelets or in the kidney is assumed to play a pathogenetic role in a variety of cardiovascular and renal diseases such as in hypertension, atherosclerosis, persistent ductus arteriosus and Bartter's syndrome.
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PMID:[Prostaglandins in cardiovascular and renal function. Biochemical, physiological and clinical findings (author's transl)]. 10 97

This review provides a summary and assessment of research involving renal prostaglandins. Arachidonic acid released from phospholipids is converted by prostaglandin cyclo-oxygenase in the kidney to PGF2, PGF2alpha, PGD2, and, possibly, to PGI2 and thromboxane A2. Production of PGE2 and PGF2alpha is predominately but not exclusively in the medulla, whereas degradative enzymes are present in both cortex and medulla. Prostaglandins enter the tubular lumen by facilitated transport and are partially reabsorbed from the urine in the distal nephron. Urine prostaglandins probably reflect renal synthesis. PGE2 and endoperoxides stimulate and PGF2alpha and indomethacin inhibit renal renin synthesis. In response to ischemia, vasoconstriction, or angiotensin II the kidney increases prostaglandin synthesis to modulate renal vascular resistance. In conscious animals or man no role has been established for prostaglandins in the maintenance of basal renal blood flow or renal sodium excretion. PGE influences renal water excretion by inhibiting the action vasopressin. Despite conflicting data there is evidence that renal prostaglandins are involved either primarily or secondarily in many types of hypertension. Inhibitors of prostaglandin cyclooxygenase have been used with success in Bartter's syndrome. Conflicting results in many areas of investigation may be resolved by the use of more accurate and reliable assays, careful handling of samples, and the use of urine to further investigate renal prostaglandin synthesis.
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PMID:Prostaglandins and the kidney. 33 46

The blood pressure lowering effects on PGI2 in the normal and spontaneously hypertensive rat are described. Comparison of dose response curves for PGI2 and PGE2 indicate that PGI2 is twice as potent as PGE2 in the normal rat and 3--4 times more active in the spontaneously hypertensive rat. Furthermore PGI2 is equiactive through intracarotid and intrajugular administration indicative of the complete lack of pulmonary inactivation. These findings supported by evidence of enhanced PGI2 synthesis in aorta during hypertension support the notion that PGI2 could participate in blood pressure control mechanisms.
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PMID:Prostaglandin I2 has more potent hypotensive properties than prostaglandin E2 in the normal and spontaneously hypertensive rat. 35 98

The influence of intravenous injection of Prostacyclin (PGI2) on systemic blood pressure was investigated in conscious and anaesthetized hypertensive rats. PGI2 in doses of 1.0, 5.0 and 10.0 micrograms/kg showed a dose dependent antihypertensive effect in conscious rats with spontaneous and chronic renal hypertension. A similar response could be demonstrated in conscious rats with normal blood pressure with doses of 1.0, 10.0 and 100.0 micrograms/kg. In anaesthetized rats with acute renal hypertension or blood pressure increase, induced by continous infusion of Angiotensin II or Norepinephrine, PGI2 caused a marked decrease of blood pressure. PGI2 induced an increase of plasma renin activity in anaesthetized rats with doses of 0.1, 1.0 and 10.0 micrograms/kg. These findings support the suggestion of an antihypertensive role for PGI2 in experimental hypertension.
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PMID:Antihypertensive effect of prostacyclin (PGI2) in experimental hypertension and its influence on plasma renin activity in rats. 36 7

The characterization of newly found unstable metabolites of arachidonic acid has provided new perspectives for cardiovascular regulatory mechanisms and new insights into disorders of the circulatory system. Since these intermediates are often more potent on and more specific for cardiovascular structures than the classical prostaglandins, they are more likely candidates as physiologic mediators of circulatory events. Their instability in vitro need not preclude these roles; on the contrary, the limited pharmacology described to date suggests that they function purely as local hormones. As such, changes in the rate of generation of these unstable but potent compounds would provide an excellent control system. The stable prostaglandins may represent only overflow of degradation products of the active mediators associated with pathologic events. For example, the dicovery of prostacyclin and the realization that this prostaglandin and not PGE2 is the primary metabolite of arachidonic acid in blood vessels emphasizes the need to reinterpret many of the previously held hypotheses that proposed that prostaglandins of the E series contributed to the regulation of vessel tone and blood pressure, Moreover, the contribution made by abnormal prostaglandin mechanisms to hypertensive disease should now take into account that a deficiency of prostacyclin and not PGE2 could be a major factor causing the elevated tension developed in vascular smooth muscle and the augmented vessel responsiveness to stimuli associated with hypertension.
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PMID:Prostaglandins, their intermediates and precursors: cardiovascular actions and regulatory roles in normal and abnormal circulatory systems. 37 96

Intravenous bolus injection of prostaglandin I2 in the Inactin-anaesthetised rat produces a slow dose-dependant vasodepression which reaches maximum approximately 15 s. after injection. Administration of 9 beta-[3H1]-prostaglandin I2 by the same route followed by serial arterial sampling and TLC analysis revealed a slow conversion into one less polar metabolite starting after 20 s and reaching 40% by two minutes in the circulation. These experiments indicate that prostaglandin I2 survives pulmonary transit for a sufficiently long time to elicit a biological action. Thus its continuous systemic vascular synthesis could play an important role in the control of hypertension.
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PMID:Comparison between the in vivo rate of metabolism of prostaglandin I2 and its blood-pressure-lowering response after intravenous administration in the rat. 38 57

Two patients with the hemolytic uremic syndrome were treated with plasma exchange an infusion: in both cases, the reduced platelet count reverted to normal values and the microangiopathic anemia ceased within a few days. Systemic blood pressure and requirement for antihypertensive drug therapy were also markedly reduced following treatment with plasma. Venousprostacyclin (antiplatelet aggregating) activity was undetectable in both patients before but was restored after treatment with plasma. The plasma samples collected before, but not those collected at various intervals after replacement therapy, had decreased capacity to stimulate prostacyclin activity in rat aortic rings. It is suggested that in patients with the hemolytic uremic syndrome or with other clinical conditions which can be included under this rubric (such as thrombotic thrombocytopenic purpura) a plasma factor is lacking which stimulates prostacyclin activity. Plasma would supply such a missing factor, thus representing a rational treatment for some of the life-threatening manifestations (thrombocytopenia, hemolytic anemia, hypertension) of this severe syndrome.
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PMID:Treatment of the hemolytic uremic syndrome with plasma. 39 47

Tranylcypromine (TCP) is a monoamine oxidase inhibitor used extensively in the treatment of patients with reactive depression. Hypertensive crisis can complicate drug therapy, but the mechanism through which TCP causes high blood pressure is unknown. The present study was undertaken because recent investigations have shown that TCP can inhibit production of a potent vasodilator hormone, prostacyclin (PGI2), by blood vessels, possibly explaining the mechanism of pressor effects by the drug. Heart rate, left atrial, pulmonary artery and aortic pressures were monitored in dogs under control conditions and continuously following the IV infusion of TCP at the rate of 1 mg/kg over a period of one minute. Right femoral and the left internal mammary arteries were obtained during the control period and the left femoral and right internal mammary arteries resected between 6 and 30 minutes following drug infusion for PGI2 studies. Concentrations of the drug that caused significant elevation of the mean systemic pressure to 203 +/- 8 mmHg had no inhibitory effect on PGI2 production. Therefore, the influence of TCP on the hemodynamic parameters does not appear to be mediated through the inhibition of vascular PGI2 synthesis.
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PMID:Tranylcypromine induced hypertension is not mediated by the inhibition of prostacyclin synthesis. 39 90

1. In corticosterone-induced hypertension in rats the activity of the peripheral sympathetic nervous system and its modulation by prostaglandins was studied. 2. Plasma concentrations of noradrenaline were reduced if compared with those in normotensive control rats. 3. The sensitivity of the isolated perfused hind-limb preparation to noradrenaline was enhanced before blood pressure rose and increased further with the development of hypertension. 4. Arachidonic acid, prostacyclin (prostaglandin I2), but not 6-keto-prostaglandin F1 alpha, reversed the supersensitivity to noradrenaline. 5. These results suggest that corticosterone induces a supersensitivity to noradrenaline by inhibiting the biosynthesis of prostaglandins. Changes in the sensitivity of the vascular smooth muscle may play a role in the development of glucocorticoid hypertension.
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PMID:Modulation of sympathetic vascular tone by prostaglandins in corticosterone-induced hypertension in rats. 54 Apr 39


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