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

Hypertension is the main side effect developing in patients suffering from renal anemia who are treated with recombinant human erythropoietin (rhEPO). We investigated the effect of rhEPO on the vascular tone of rabbit aorta. rhEPO had no direct vasoconstrictor effect, but it enhanced norepinephrine (NE)-induced contractions of rabbit aortic rings. Relaxations to acetylcholine (ACh, 1 microM) were unaltered in the presence or absence of rhEPO, indicating that the endothelium-dependent NO pathway was not affected by rhEPO. In rings of human renal artery and rabbit aorta, rhEPO (200 U/ml) increased the synthesis of constrictor prostanoids. The cyclooxygenase inhibitors indomethacin and aspirin abolished the increase in prostanoid production. However, they did not completely suppress the rhEPO-induced enhancement of NE contractions in rabbit aorta. We further investigated the effect of rhEPO on prostanoid and endothelin-1 synthesis in cultured human endothelial cells. Endothelial cells from human umbilical veins (HUVEC) were isolated and cultured. After incubation with rhEPO, the formation of prostaglandin (PG) I2 (analyzed as its stable metabolite 6-keto-PGF1 alpha), PGF2 alpha, PGE2, thromboxane (Tx) B2, and of endothelin-1 (ET-1) was measured by radioimmunoassay (RIA). rhEPO (200 U/ml) increased the formation of PGF2 alpha and TxB2 and decreased the formation of PGI2 in HUVEC. The release of ET-1 was increased by nearly 90% in the presence of rhEPO (200 U/ml). We conclude that a shift in the balance of constrictor and relaxing prostanoids as well as an increased synthesis of ET-1 may contribute to the hypertensive side effect of rhEPO therapy. ET-1 may at least in part be responsible for the unexpectedly low inhibitory effect of indomethacin on rhEPO-enhanced contractions of rabbit aorta.
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PMID:Endothelin release and shift in prostaglandin balance are involved in the modulation of vascular tone by recombinant erythropoietin. 128 78

Prostaglandins participate in the regulation of blood pressure in normotensive and hypertensive subjects; vascular tone is subject to the continuous relaxing influence of endogenous vasodilating prostaglandins. Prostaglandin I2 (PGI2; prostacyclin), probably the most important physiological modulator of vascular tone, decreases blood pressure together with a concomitant increase in cardiac output and a reduction in systemic vascular resistance secondary to peripheral vasodilation. In addition, vasodilation within the splanchnic, pulmonary and coronary vascular beds has been observed, with increased blood flow through the mesenteric, renal and coronary vascular beds. These changes in regional blood flow have been associated with the inhibition, by PGI2, of the vasoconstrictor response to sympathetic nervous stimulation and pressor hormones [noradrenaline (norepinephrine), angiotensin II]. However, other prostaglandins, such as prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha), induce coronary vasoconstriction and have different effects on pulmonary artery blood pressure because of their effect on pulmonary vascular resistance. Nonsteroidal anti-inflammatory drugs (NSAIDs; e.g. indomethacin) have been reported to induce hypertension parallel to a fall in cardiac output, suggesting that the underlying mechanism is an increase in systemic vascular resistance. In animal models these agents reduced regional blood flow in the ischaemic myocardium, with a corresponding increase in infarct size. Ibuprofen, which inhibits prostaglandin synthesis to a lesser extent than indomethacin, did not exert systemic or coronary haemodynamic effects. NSAIDs also provide protection in shock models but may exacerbate haemodynamic derangements and decrease survival in acute hypovolaemic hypotension. To what extent do NSAIDs and opioids influence cardiovascular status during the postoperative course and analgesic therapy? Continuous infusion of NSAIDs for analgesia had no major haemodynamic effects. Also, there were insignificant changes in indices of left heart function (cardiac output, stroke volume) and the systemic circulation (mean arterial pressure, systemic vascular resistance) following intravenous ketorolac injections, whereas cardiac output and mean arterial pressure decreased after administration of morphine. The pulmonary circulation was unaffected by ketorolac administration, whereas morphine administration induced an increase in pulmonary vascular resistance. Indices of right and left cardiac work were decreased by morphine. Thus, ketorolac produces fewer haemodynamic effects than morphine, although it is possible that some of the effects of morphine may result from morphine-induced histamine release. NSAIDs may be seen as a worthwhile gain with respect to morphine in clinical situations when hypotension is disadvantageous or when reduction in afterload is not a specific therapeutic aim.
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PMID:Cardiovascular risks and benefits of perioperative nonsteroidal anti-inflammatory drug treatment. 128 61

The short term effect of anisodamine, an alkaloid isolated from the chinese herb anisodas tonguticus, on blood flow of uterine and umbilical arteries in 16 pregnant women with pregnancy-induced hypertension (PIH) was investigated by means of pulsed doppler ultrasound technique Results have shown that anisodamine could decrease the A/B ratio, resistant index (RI), and pulsative index (PI) of blood velocity in these arteries with statistical significant difference. Its mechanism of action might be the improving of the rheology in PIH and adjusting the imbalance of TXA2/PGI2. It was suggested that the resistance in uteroplacental circulation was decreased and its perfusion improved, so that favors the fetal growth and development.
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PMID:[Mechanism and effect of anisodamine on uteroplacental circulation in pregnancy-induced hypertension]. 129 Dec 19

Intrarenal hemodynamic and tubular function has been assessed in 16 patients who presented clinically with hypertension, hematuria and severe renal functional impairment. Twelve of these 16 patients had histopathologic classification as DPGN (3 cases), MPGN (3 cases) and FSGS (6 cases). The initial assessment of intrarenal hemodynamics in 11 patients revealed strikingly increased afferent (RA) and efferent arterioles (RE), filtration fraction (FF), intraglomerular capillary hydrostatic pressure (PG), whereas, there was marked reduction in renal plasma flow (RPF), in ultrafiltration coefficient (KFG) and in glomerular filtration rate (GFR). Tubular transporting defect as being reflected by enhanced fractional excretions of solutes was also observed. Both enhanced TXB2 production and diminished PGI2 may be in part responsible for the marked reduction of RPF and elevated intrarenal resistance. In light of the preceding intrarenal hemodynamics alteration, therapeutic intervention with vasodilators consisting of dipyridamole, calcium channel blocker and angiotensin convertase inhibitor has been accomplished with clinical improvement in glomerular and tubular functions following the improvement in intrarenal hemodynamics. Thus, this abnormal intrarenal hemodynamics renders a supportive view of the hemodynamically mediated glomerulo-tubulo-interstitial injury to be central to the pathogenetic mechanism.
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PMID:Intrarenal hemodynamic abnormality in severe form of glomerulonephritis: therapeutic benefit with vasodilators. 129 54

After two weeks' treatment of indapamide (2.5 mg/d) in 30 cases of mild to moderate hypertensive patients, there was a significant decline of systolic and diastolic blood pressure. And 8 weeks after indapamide administration, 2/3 of the total treated patients achieved complete control of hypertension. During the treatment period, there were no changes of serum cholesterol, triglyceride and renal function, except a slight, but still in the normal range, decrease of serum potassium and sodium. Concurrently, plasma vasoconstrictive prostaglandins TXB2 (metabolite of TXA2) and PGF2 alpha reduced significantly (P < 0.01 and P < 0.001 respectively), whereas plasma vasodilative prostaglandins 6-keto-PGF1 alpha (metabolite of PGI2) and PGE2 increased significantly (P < 0.02 and P < 0.05 respectively). The results support the theory that prostaglandins system may play an important role in the hypotensive process of indapamide. The influence of indapamide on prostaglandin system may favour the improvement of platelet function and the maintenance of the homeostasis.
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PMID:[The effect of indapamide on plasma prostaglandins in hypertensive patients]. 130 70

1. Pregnancy-induced hypertension (or pre-eclampsia) is characterized by vasoconstriction, platelet aggregation and altered capillary permeability, implying disordered endothelial function and/or structure. Serum from women with pregnancy-induced hypertension has been reported by others to be cytotoxic to endothelial cells in vitro. We hypothesized that such serum contains a factor that limits the ability of endothelial cells to produce and/or release prostacyclin. 2. Prostacyclin production by intact and damaged cultured human umbilical vein endothelial cells was measured after incubating these cells with serum from non-pregnant and normal pregnant women and women with pregnancy-induced hypertension. Confluent human umbilical vein endothelial cell monolayers (intact and damaged) were incubated with sera for 24 h at 37 degrees C followed by 1 h of incubation with added thrombin (stimulated production) or media (basal production). Supernatants were then collected for measurement of 6-keto-prostaglandin F1 alpha by radioimmunoassay. 3. Basal production of 6-keto-prostaglandin F1 alpha was greater in response to serum from non-pregnant women than to that from pregnant women. Within each group, sub-lethally damaged cells had a similar basal production of 6-keto-prostaglandin F1 alpha to that of intact cells. 4. Basal production of 6-keto-prostaglandin F1 alpha by intact or damaged cells incubated with sera from normal pregnant women and from women with pregnancy-induced hypertension was similar. 5. In all groups the addition of thrombin to intact endothelial cells increased 6-keto-prostaglandin F1 alpha production approximately 15-30-fold over basal levels, but only three- to five-fold in damaged endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelium-derived prostacyclin: effect of serum from women with normal and hypertensive pregnancy. 131 48

The pathogenesis of hypertension in autosomal-dominant polycystic kidney disease (ADPKD) is unclear, but increased activity of the renin-angiotension system may contribute. The renal and systemic hemodynamic response to lisinopril, an angiotension converting enzyme (ACE) inhibitor, in patients with ADPKD without renal failure was compared with the response in matched unaffected family members. Mean blood pressure and renal vascular resistance decreased in the affected group after lisinopril, with no significant change in the unaffected group. Glomerular filtration rate (GFR) was unchanged and therefore filtration fraction fell significantly. Changes in urinary excretion of 6-keto-PGF1 alpha and kallikrein suggested that increased renal synthesis of PGI2 or activation of the renal kallikrein-kinin system were not likely to be responsible for the hemodynamic effects. The acute decrease in renal vascular resistance without change in GFR suggests that ACE inhibition may have a particular value in the treatment of hypertension associated with ADPKD which should be assessed by further long-term studies.
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PMID:Effects of angiotensin converting enzyme inhibition in adult polycystic kidney disease. 131 77

The purpose of this study was to gain insight into the mechanism(s) responsible for the exaggerated angiotensin II (ANG II)-induced renal vasoconstriction during the development of hypertension. In previous studies we observed that ANG II produces a twofold larger decrease in renal blood flow (RBF) in spontaneously hypertensive (SHR) compared with Wistar-Kyoto (WKY) rats before but not after cyclooxygenase inhibition. We suggested that this strain difference could be attributed to differences in renal prostaglandin (PG) levels and/or action. To evaluate these possibilities, measurements of RBF were made in 6-wk-old, anesthetized SHR and WKY pretreated with indomethacin. ANG II was injected intrarenally before and during continuous intrarenal infusion of a low dose of PGE2, viprostol (PGE2 analogue), PGI2, iloprost (PGI2 analogue), and bradykinin. In the control period ANG II reduced RBF by 50% in both strains. Infusion of PGs reduced the vasoconstrictor effect of ANG II in WKY, but had no effect in SHR. In contrast, infusion of bradykinin blunted the ANG II-induced vasoconstriction to a similar degree in both WKY and SHR. To investigate whether this lack of protection in SHR is due to strain differences in the number and/or affinity of renal receptors of PGs, radiolabeled ligand binding studies for PGE2 and PGI2 receptors were undertaken in glomeruli isolated from young WKY and SHR. Scatchard analysis revealed a single, high-affinity receptor site for PGE2 that was similar in both strains of rats. Both strains also exhibited a single, high-affinity PGI2 receptor site. No differences were observed in the PGE2 or PGI2 receptor number between WKY and SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired ability of prostaglandins to buffer renal vasoconstriction in genetically hypertensive rats. 132 56

Endothelial cells produce the 21-amino acid peptide endothelin, which is formed from its precursor, big endothelin, via the activity of converting enzyme. The basal production of the peptide is stimulated by epinephrine, angiotensin II, arginine vasopressin, transforming growth factor beta, thrombin, interleukin-1, and hypoxia. In vascular smooth muscle, endothelin binds to a specific receptor (ETA-subtype), which activates phospholipase C, leads to the formation of inositol trisphosphate, diacylglycerol (which activates protein kinase C), and increased intracellular Ca2+. In certain blood vessels, the endothelin receptor on vascular smooth muscle is linked to a voltage-operated Ca2+ channel via a G-protein. This explains why Ca2+ antagonists inhibit endothelin-induced contractions in certain, but not all, blood vessels. In the human forearm circulation, Ca2+ antagonists do prevent endothelin-induced contractions and unmask endothelin-induced vasodilation mediated by endothelial prostacyclin production (via the ETB-receptor). The pulmonary circulation plays an important role in the metabolism of endothelin, as the lungs take up large quantities of the peptide during passage. Endothelin has profound vasoconstrictor effects in the pulmonary circulation (and also in bronchial tissue), and its production is augmented in pulmonary hypertension. In systemic hypertension, the circulating endothelin levels appear to be normal. In atherosclerosis and other forms of vascular disease, circulating endothelin levels are increased. Thus, endothelin is a potent mediator in the systemic and pulmonary circulation and, in particular, in diseases of the vasculature.
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PMID:Endothelin: systemic arterial and pulmonary effects of a new peptide with potent biologic properties. 133 60

Old concepts of an "inert" vascular endothelium have been entirely discredited. It is now known that the vascular endothelium and media form a "functional unit", communicating via both electric and humoral signals. Normal endothelium maintains vascular dilation through release of various dilatory substances, the main one being endothelial relaxing factor (EDRF), which is nitric oxide (NO). EDRF is, for example, released in response to increased shear stress that accompanies high flow rates, and acts by engaging the cyclic GMP system of smooth muscle cells. Even potential vasoconstrictors such as vasopressin, catecholamines and serotonin release EDRF. Endothelial release of prostacyclin supplements the EDRF action. EDRF (and prostacyclin) also inhibit platelet aggregation. In the presence of hypertension and/or atherosclerosis, endothelial function is often impaired and pressor/thrombogenic factors such as endothelin, thromboxane, vasopressin, catecholamines, and serotonin become more dominant. Antihypertensive therapy should, ideally, seek to restore endothelial function to normal.
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PMID:Hypertension and endothelial function--aspects of atheroma protection. 134 64


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