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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

The effects of topically applied prostaglandin (PG) D2 and BW245C, a potent PGD2 agonist, on intraocular pressure (IOP) were studied in normotensive human volunteers. Doses of 5 and 10 micrograms PGD2 induced a mean reduction in IOP of 0.8 and 1 mmHg, respectively. At a dose of 50 micrograms, hypotension was preceded by initial hypertension (4 mmHg at 0.5 h) and the magnitude of the mean IOP reduction during the hypotensive phase was 1.1 mmHg. The application of BW245C (2.5 micrograms) induced an IOP change similar to that observed following treatment with 50 micrograms PGD2. Side effects caused by these compounds included conjunctival hyperemia, itching, and foreign-body and mild burning sensations. However, miosis and signs of intraocular inflammation were not observed. These results indicate that although PGD2 and BW245C are effective in reducing human IOP, their clinical usefulness as anti-glaucoma drugs may be limited by the extraocular side effects.
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PMID:Effects of prostaglandin D2 and its analogue, BW245C, on intraocular pressure in humans. 193 72

To assess the participation of cardiovascular eicosanoids (prostaglandins and thromboxanes) system in the initiation of genetic hypertension, we examined eicosanoids metabolism in the heart, aortic wall and kidney in prehypertensive and hypertensive rat models for spontaneous hypertension (SHR). Vasoconstrictor thromboxane A2 (TXA2) generation in the aortic wall was significantly enhanced by 49% in the prehypertensive and by 18% in the hypertensive SHR when compared to the respective normotensive Wistar-Kyoto rats. Cardiac TXA2 content was significantly increased as well by 14% in the prehypertensive and by 30% in the hypertensive SHR. Moreover, vascular vasodepressor eicosanoids generation was decreased by 10% for PGI2 and by 29% for PGD2 in the prehypertensive SHR although the alterations were eliminated in the hypertensive SHR. In contrast to the cardiovascular eicosanoids system, there was no difference in renocortical TXA2 content in either young or adult SHR while vasodepressor prostaglandins contents were decreased by 29% for PGE2 and by 33% for PGD2 in SHR when they were in the prehypertensive stage. Thus, in the prehypertensive stage of SHR, the cardiovascular eicosanoids system exhibited enhanced vasoconstrictor TXA2 and decreased vasodepressor prostaglandins, thereby producing a vasoconstrictor state. These data indicate that the alterations in the cardiovascular eicosanoids system partially contribute to the initiation of hypertension in SHR.
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PMID:Alterations of the cardiovascular and renal prostaglandins and thromboxanes system in prehypertensive spontaneously hypertensive rats. 266 86

We designed experiments to reveal the effects of a S2 serotonergic receptor antagonist, ketanserin, on the vascular eicosanoid system and the relevance to medial hyperplasia in spontaneously hypertensive rats (SHR). 2-week ketanserin treatment (5 mg/kg/day) significantly decreased systolic blood pressure by 7% when compared to untreated SHR. The blood pressure reduction was associated with a significant decrease in vascular thromboxane A2 (TXA2) generation and sustained prostacyclin (PGI2) production, thereby shifting PGI2/TXA2 ratio toward vasodilatation. In contrast, the trichlormethiazide treatment, which achieved blood pressure reduction to almost the same extent, significantly decreased PGI2/TXA2 ratio. Vasodilator eicosanoids, e. g. PGI2, PGE2 and PGD2, dose-dependently decreased (3H)-thymidine uptake by vascular smooth muscle cells in culture whereas vasoconstrictor TXA2 enhanced (3H) thymidine uptake in a dose dependent manner. Indeed 2 x 10(-5) M ketanserin significantly decreased (3H) thymidine uptake by vascular smooth muscle cells by 48% although the same dose of methysergide, nonspecific serotonin inhibitor, did not affect the uptake by vascular smooth muscle cells. These results clearly indicate that the blood pressure reduction in ketanserin treatment is uniquely associated with a decrease in vascular thromboxane generation, and that it is possibly beneficial to protect vascular wall against medial hyperplasia of vascular smooth muscle cells, an integral component of arterial sclerotic changes in hypertension.
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PMID:[The effects of ketanserin on vascular eicosanoid system in spontaneously hypertensive rats and their implications]. 274 98

In summary, prostacyclin, PGE2, and PGD2 are vasodilators and had significantly lower renal cortical and outer medullary concentrations in the borderline hypertensive S rats compared to normotensive R rats. Conversely, thromboxane is a vasoconstrictor which had significantly higher renal cortical and outer medullary concentrations in borderline hypertensive S rats compared to normotensive R rats. Thus, in borderline hypertensive S rats, both renal cortex and outer medulla have a prostaglandin pattern which favors vasoconstriction in cortical vessels and in descending vasa recta. This could partially account for the increased renal vascular resistance and low papillary plasma flows which are integral components of Dahl hypertension. The low PGE2 in S kidneys would also enhance Na reabsorption in collecting tubules and ascending limbs, thereby encouraging Na retention and hypertension.
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PMID:Prostaglandin alterations in barely hypertensive Dahl S rats. 384 5

Effect of furosemide at various concentrations (0.05-4 mM) was examined on the in vitro biosynthesis of prostaglandins in human platelets. At lower furosemide concentrations (0.05 and 0.1 mM) no effect was observed. At 1 and 2 mM concentrations, PGE2 significantly (P less than 0.01) increased. At 3 and 4 mM concentrations PGE2 increased though not significantly probably because of the small number of samples (n=5). A decrease in PGD2 formation was noted at 1-4 mM furosemide concentrations, though significantly only at 3 mM conc. At 1 and 2 mM concentrations, TxB2 and HHT increased whereas at 3 and 4 mM concentrations these metabolites were decreased. These effects were, however, not significant. No effect was observed on endoperoxide generation at 1 and 2 mM conc. Furosemide at 1 and 2 mM concentrations inhibited ADP- and arachidonic acid induced platelet aggregation. An increased platelet formation of PGE2 in the presence of furosemide may point to the fact that this drug shows its effect mainly on the formation of PGE2 which has been found to exert a profound effect on renal blood flow and thus ameliorates some forms of hypertension.
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PMID:Effect of furosemide on the in vitro prostaglandin biosynthesis in human platelets. 681 95

Renal prostaglandins play a role in the control of renin release during chronic sodium depletion, during the acute phase of renovascular hypertension and in experimental low output heart failure in conscious dogs. However, with marked inhibition of the renin-angiotensin system, the adrenergic nervous system and the renal prostaglandins, PRA was still 17 times normal during chronic sodium depletion. After blockade of the adrenergic nervous system and the renal prostaglandins, PRA was 10 times normal during the acute phase of one-kidney renovascular hypertension. These findings demonstrate that other important mechanisms, possibly both the renal vascular receptor (so-called baroreceptor) and the macula densa, were involved. Both PGI2 and PGD2 given intrarenally increased renin release in both filtering and nonfiltering kidneys, but PGI2 was more potent than PGD2. Available evidence favors a role of PGI2 and it seems likely that the site of action is on the JG cells. Indomethacin produced a profound drop in CCr and CPAH during sodium depletion and in experimental heart failure which demonstrates an important role for the renal prostaglandins in the control of renal arteriolar tone. An important incidental finding is that renal denervation combined with propranolol administration decreased PRA from very high levels to normal in 50% of the dogs with experimental low output heart failure and a concurrent striking natriuresis occurred.
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PMID:Renal prostaglandins, renin release, and renal hemodynamic function in high renin states. 700 Apr 61

Lipocalin-type prostaglandin D synthase (L-PGDS) reportedly well predicts cardiovascular injuries in humans. However, little is known about the implications of L-PGDS in hypertension. In the present study, we investigated the alterations of serum and urinary L-PGDS in hypertensive patients with or without renal dysfunction. A total of 111 patients with hypertension (EHT; 65 with normoalbuminuria, 23 with microalbuminuria, 12 with macroalbuminuria, 11 with renal failure) and 102 normotensive, nomoalbuminuric subjects (NT) were studied. L-PGDS was measured by enzyme-linked immunosorbent assay, and L-PGDS in the kidney was localized using immunohistochemical methods. Blood pressure was higher in EHT groups than in the NT group (P<0.0001). There were no differences in age, gender, BMI, TC, TG, and HbA1c levels among the groups. Serum creatinine and urinary albumin levels were higher in the group with renal failure. Serum levels of L-PGDS were increased in EHT with normoalbuminuria, as compared with NT (0.88 +/- 0.05 versus 0.65 +/- 0.02 microg/mL; P<0.001). Serum levels of L-PGDS increased with the renal function worsened and positively correlated with serum creatinine, particularly in patients with renal impairments (r=0.76, P<0.0001). Similarly, the urinary L-PGDS excretions in EHT with normoalbuminuria were higher than that in NT (2.31 +/- 0.29 versus 1.16 +/- 0.14 mg/gCr, P<0.001), whereas there were no differences in urinary albumin excretion between the 2 groups. Moreover, urinary L-PGDS excretion increased dramatically with an increase in albuminuria or proteinuria. L-PGDS was stained in the tubules and the interstitium of the kidney in nephrosclerosis. In conclusion, patients with hypertension exhibited a higher level of L-PGDS in serum and urine, and this became increasingly obvious along with advance in renal dysfunction. These data suggest that L-PGDS metabolism is related to blood pressure and kidney injuries associated with hypertension.
Hypertension 2002 Feb
PMID:Lipocalin-type prostaglandin d synthase in essential hypertension. 1188 88

Lipocalin-type prostaglandin D2 synthase (L-PGDS) has recently been linked to a variety of pathophysiological cardiovascular conditions including hypertension and diabetes. In this study, we report on the 50% increase in L-PGDS protein expression observed in vascular smooth muscle cells (VSMC) isolated from spontaneously hypertensive rats (SHR). L-PGDS expression also increased 50% upon the differentiation of normotensive control cells (WKY, from Wistar-Kyoto rats). In addition, we demonstrate differential effects of L-PGDS treatment on cell proliferation and apoptosis in VSMCs isolated from SHR versus WKY controls. L-PGDS (50 microg/ml) was able to significantly inhibit VSMC proliferation and DNA synthesis and induce the apoptotic genes bax, bcl-x, and ei24 in SHR but had no effect on WKY cells. Hyperglycemic conditions also had opposite effects, in which increased glucose concentrations (20 mm) resulted in decreased L-PGDS expression in control cells but actually stimulated L-PGDS expression in SHR. Furthermore, we examined the effect of L-PGDS incubation on insulin-stimulated Akt, glycogen synthase kinase-3beta (GSK-3beta), and ERK phosphorylation. Unexpectedly, we found that when WKY cells were pretreated with L-PGDS, insulin could actually induce apoptosis and failed to stimulate Akt/GSK-3beta phosphorylation. Insulin-stimulated ERK phosphorylation was unaffected by L-PGDS pretreatment in both cell lines. We propose that L-PGDS is involved in the balance of VSMC proliferation and apoptosis and in the increased expression observed in the hypertensive state is an attempt to maintain a proper equilibrium between the two processes via the induction of apoptosis and inhibition of cell proliferation.
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PMID:Prostaglandin D2 synthase inhibits the exaggerated growth phenotype of spontaneously hypertensive rat vascular smooth muscle cells. 1268 6

Prostanoids, consisting of the prostaglandins (PGs) and thromboxanes (TXs), exert various actions through activation of their specific receptors. They include the DP, EP, FP, IP, and TP receptors for PGD2, PGE2, PGF2alpha, PGI2, and TXA2, respectively. Moreover, EP receptors are classified into four subtypes, the EP1, EP2, EP3 and EP4 receptors. Using mice lacking prostanoid receptors, we intended to clarify in vivo roles of prostanoids under pathophysiological conditions of the cardiovascular system, which include ischemia-induced cardiac injury, pressure overload-induced cardiac hypertrophy, renovascular hypertension, tachycardia during systemic inflammation and thromboembolism. The results demonstrated that 1) PGI2 plays an important role in attenuating the ischemic injury and the pressure overload-induced hypertrophy of the hearts, and also contributes to the development of renovascular hypertension; 2) PGE2 plays a cardioprotective role against the ischemic injury via both the EP3 and EP4, and also participates in acute thromboembolism via the EP3; and 3) both PGF2alpha and TXA2, which have been produced during systemic inflammation, are responsible for tachycardia.
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PMID:[Pathophysiological roles of the prostanoids in the cardiovascular system: studies using mice deficient in prostanoid receptors]. 1456 57


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