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

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

Vascular relaxations are impaired in adult spontaneously hypertensive rats (SHRs) because of increased production of endothelium-derived, cyclooxygenase-dependent contractile factors. The objectives of the present study were to determine whether alterations in endothelial function precede the development of hypertension in SHRs and to characterize the contractile factor(s) produced by SHR endothelial cells. Mean systolic blood pressures were minimally (6 mm Hg) higher at 4 weeks of age in SHRs than in Wistar-Kyoto (WKY) rats. Endothelium-mediated relaxations of mesenteric and renal resistance arteries from SHRs and WKY rats were compared in myographs and arteriographs in paired experiments. Acetylcholine (ACh, 10(-9) to 10(-7) M) induced endothelium-dependent relaxations in precontracted mesenteric and renal resistance arteries that were similar in SHRs and WKY rats. At higher concentrations of ACh (10(-6) to 10(-5) M), relaxations were replaced by contractile responses in SHR but not in WKY rat resistance arteries. The contractile responses were endothelium dependent and were inhibited by indomethacin in both mesenteric and renal arteries. Thus, endothelial dysfunction precedes and may contribute to the development of accelerated hypertension in SHRs. SQ 29548, a prostaglandin H2 (PGH2)-thromboxane A2 receptor antagonist, blocked the contractile responses in renal but not in mesenteric resistance arteries. The contractile responses in mesenteric arteries were inhibited by 3-amino-1,2,4-triazole (10(-3) M), an inhibitor of superoxide production via the cyclooxygenase pathway. We conclude from these data that the endothelium-derived contracting factor (EDCF) produced in SHR renal arteries is most likely PGH2 whereas the contractile factor produced in mesenteric arteries is superoxide.
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PMID:Endothelial dysfunction of resistance arteries of spontaneously hypertensive rats. 128 66

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

Little is known about the effect of low dose, enteric-coated aspirin on human blood platelet function. This study was conducted to evaluate the acute effects of a single daily dose of commercially available enteric-coated aspirin on platelet biochemistry, physiology and function. Blood for these studies was obtained from drug-free volunteer donors prior to ingestion of aspirin or following ingestion, either before breakfast or following lunch. Response of platelets to the action of weak agonists was evaluated. In addition, ability of platelets to convert radiolabeled arachidonic acid to thromboxane was monitored. Results of our studies show that a single daily dose of 50 mg of aspirin taken either before breakfast or after lunch effectively prevented the secondary wave aggregation response, as well as secretion of dense body contents when stimulated by agonists such as epinephrine and ADP. Aspirin ingestion caused a dose-dependent inhibition of platelet cyclooxygenase activity as evidenced by the extent of arachidonic acid converted to thromboxane by platelets exposed to aspirin for different time periods. Based on these observations, it is suggested that low dose aspirin may be very useful and desirable to restrain platelet activity in clinical situations in which increased thromboxane formation may initiate vascular hypertension and platelet hyperactivity.
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PMID:Influence of low dose enteric-coated aspirin on platelet function. 130 83

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

The present study investigated the role of arachidonic acid and acetylcholine in mediating endothelium-dependent relaxations of rabbit aorta. Isolated thoracic aortic rings were precontracted with a submaximal concentration of norepinephrine, and the effect of various agents on arachidonic acid- and acetylcholine-induced relaxations was examined. Arachidonic acid elicited a concentration-related relaxation that was potentiated by the cyclooxygenase inhibitor indomethacin. Treatment with the lipoxygenase inhibitor nordihydroguaiaretic acid completely blocked but the cytochrome P450 inhibitor metyrapone had no effect on arachidonic acid-induced relaxation. NG-Monomethyl-L-arginine and nitro-L-arginine, compounds that inhibit the nitric oxide-like endothelium-derived relaxing factor, had little or no effect on arachidonic acid-induced relaxations. In contrast, nordihydroguaiaretic acid, metyrapone, NG-monomethyl-L-arginine, and nitro-L-arginine all attenuated the relaxation to acetylcholine; however, indomethacin had no effect on acetylcholine-induced relaxations. Arachidonic acid and acetylcholine had no effect on denuded rabbit aorta. Incubation of rabbit aorta with [14C]arachidonic acid resulted in the synthesis of major radioactive metabolites that comigrated with the prostaglandins and hydroxyeicosatetraenoic acids. Indomethacin selectively inhibited prostaglandin formation, nordihydroguaiaretic acid attenuated both prostaglandins and hydroxyeicosatetraenoic acids, and metyrapone blocked the epoxyeicosatrienoic acids. Additionally, acetylcholine elicited a twofold increase in tissue cyclic guanosine monophosphate content in contrast to a 59% reduction in cyclic guanosine monophosphate content observed with arachidonic acid. Therefore, these data suggest that in rabbit aorta, arachidonic acid-induced relaxations are mediated by an endothelium-dependent factor (or factors) that differs from the factor (or factors) released by acetylcholine. These results support the existence of multiple endothelium-derived relaxing factors.
Hypertension 1992 Nov
PMID:Arachidonic acid- and acetylcholine-induced relaxations of rabbit aorta. 133 Sep 23

The influence of endothelium on the direct contractile effects of ouabain in vascular smooth muscle was analyzed in isolated perfused guinea pig carotid arteries. After blocking the neurogenic component of the glycoside contraction with alpha-adrenergic receptor blocking drugs or treating the animals with reserpine, ouabain-induced contractions were markedly reduced in vessels with intact endothelium. However, removal of the vascular endothelium from reserpinized carotid arteries resulted in ouabain-induced contractions similar to those observed in control arteries. These effects were not mimicked by the inhibitor of nitric oxide NG-monomethyl L-arginine or by the cyclooxygenase blocker indomethacin. Bioassay experiments suggested that these endothelial effects are mediated by diffusible factors. Uptake of 86Rb to measure sodium pump activity was significantly reduced by removal of the endothelium. These results suggest the existence of an inhibitory modulation by the endothelium of contractions induced by ouabain, likely mediated by a diffusible factor (or factors) released from these cells. The nature of this substance is unknown, but it is neither related to prostaglandins nor a nitric oxide-related compound. Its mechanism of action could be the stimulation of vascular sodium pump activity, the antagonism of the pump's inhibition by ouabain, or both.
Hypertension 1992 Nov
PMID:Endothelial role in ouabain-induced contractions in guinea pig carotid arteries. 135 23

The balance between prostaglandin (PG)I2, a potent vasodilator and inhibitor of platelet aggregation mainly produced by endothelial cells, and thromboxane (TX)A2, a vasoconstrictor and inducer of platelet aggregation and adhesion synthesized predominantly by platelets, seems to be relevant for the regulation of vessel tone and platelet aggregation. PGE2 has vasodilating properties, too. Thus, substances affecting the biosynthesis of PG and TX may have prophylactic and therapeutic, but also detrimental effects with regard to hypertension and atherosclerosis. A mechanism of action which is related to the PG system is discussed for a number of antihypertensive agents, e.g. propranolol, angiotensin converting enzyme inhibitors, furosemide and cicletanine. The vasoprotective effect of inhibition of platelet cyclooxygenase by acetylsalicylic acid is well known. Calcium antagonists, dipyridamole, estradiol, aprotinin and interferon have also been reported to possibly exert beneficial effects on PG/TX levels, while cyclosporin A and streptokinase have shown undesirable interactions with the PG system.
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PMID:[Vasoactive drugs with an effect on the prostaglandin system]. 141 11

We investigated the role of prostanoids in the constrictor effect of calcium ionophore A23187, endothelin-1 and vasopressin in rings of thoracic aorta obtained from normotensive rats and rats with aortic coarctation-induced hypertension. Isometric tension was measured in aortic rings bathed in buffer with and without indomethacin (10 microM), CGS13080 (10 microM) or SQ29548 (1 microM) to inhibit cyclooxygenase and thromboxane synthase and to block TxA2-PGH2 receptors, respectively. Increases in tension elicited by A23187 and vasopressin in aortic rings from hypertensive rats exceeded responses in rings from normotensive rats. A23187-induced contractions were virtually abolished by indomethacin and SQ29548, and slightly attenuated by CGS13080. These agents also attenuated the contractions elicited by endothelin but not by vasopressin. According to these data, a prostanoid(s) agonist for TxA2-PGH2 receptors contributes to the constrictor effect of A23187 in aortic rings of hypertensive rats, and of endothelin in aortic rings of normotensive and hypertensive rats. Moreover, the expression of prostanoid-mediated contractions as it pertains to the aortic response to A23187 is greatly increased in hypertensive rats.
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PMID:Prostanoid-mediated vascular contraction in normotensive and hypertensive rats. 142 79

In addition to cyclooxygenase and lipoxygenase, arachidonic acid (AA) is metabolized by the cytochrome P-450 monooxygenase system. The kidney is one of the major extrahepatic tissues that display cytochrome P-450 enzyme activities, in particular the cortex, specifically the proximal tubule demonstrate the highest concentration. AA is metabolized by the renal cytochrome P-450 epoxygenase and omega/omega 1 hydroxylases to epoxyeicosatrienoic acids and omega/omega-1 alcohols (20- and 19-mono-hydroxyeicosatetraenoic acids), respectively. These metabolites possess a broad spectrum of biological and renal effects which include: vasodilation, vasoconstriction, inhibition and stimulation of Na(+)-K(+)-ATPase, inhibition of ion transport mechanisms, natriuresis, inhibition of renin release and stimulation of cell growth. These metabolites are endogenous constituents of the kidney and are present in urine with increasing concentration under pathological conditions such as pregnancy-induced hypertension. The cytochrome P-450-dependent metabolism of AA is specifically localized to the proximal tubule and exhibits developmental changes, i.e., renal production of metabolites is very low in the fetus, newborn and up to 3 weeks of age, after which a remarkable increase in enzyme activities is observed. These characteristics call attention to the importance of this enzyme system in producing cellular mediators for regulating renal function in normal and diseased states.
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PMID:The renal cytochrome P-450 arachidonic acid system. 145 35


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