Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of recombinant human erythropoietin (r-HuEPO, 0.1 to 2.0 U/ml) on endothelin-1 (ET-1) release was examined in isolated hind legs perfused with Krebs-Ringer solution from normal rats. r-HuEPO increased immunoreactive (ir-) ET-1 release in a dose-dependent fashion; the maximal percent increment in ir-ET-1 release evoked by r-HuEPO (2.0 U/ml) was about +210% over the basal rate of release. However, r-HuEPO showed no effect on release of angiotensin II, thromboxane B2 or vasodilatory prostaglandin I2 from the vasculature. These results not only provide direct evidence that r-HuEPO has the potential to specifically stimulate release of ET-1 from peripheral vascular beds, but, hence, suggest a contributory role of ET-1 in r-HuEPO-induced hypertension in anemic human subjects undergoing r-HuEPO therapy.
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PMID:Direct evidence for erythropoietin-induced release of endothelin from peripheral vascular tissue. 815 33

The purpose of this study was to compare the effects of prostaglandin I2 on several cardiovascular parameters and to compare the ability of prostaglandin I2 to modify angiotensin II-induced changes in these cardiovascular parameters in spontaneously hypertensive versus normotensive rats. Studies were conducted in adult, age-matched, indomethacin-, and captopril-pretreated spontaneously hypertensive and normotensive rats that had been prepared for assessment of arterial blood pressure, cardiac output (thermodilution), and renal and mesenteric blood flows (transit-time flow probes). In both normotensive and hypertensive rats, intravenous infusions of prostaglandin I2 (0.003, 0.03, 0.3, 1, 3, and 10 micrograms/kg per minute) dose-dependently reduced mean arterial blood pressure, total peripheral resistance, and mesenteric vascular resistance but not renal vascular resistance. Only minor differences were detected between normotensive versus hypertensive rats with regard to the effects of prostaglandin I2 on baseline cardiovascular parameters (ie, in the absence of angiotensin II). In both rat strains, an intravenous infusion of angiotensin II (300 ng/kg per minute) increased mean arterial blood pressure, total peripheral resistance, and renal and mesenteric vascular resistances, and these effects of angiotensin II were similar in the two strains in the absence of prostaglandin I2. In both strains, prostaglandin I2 inhibited angiotensin II-induced changes in mean arterial blood pressure, total peripheral resistance, and renal and mesenteric vascular resistances. However, in the renal, but not mesenteric, vasculature of hypertensive rats, the ability of prostaglandin I2 to attenuate angiotensin II-induced vasoconstriction was strikingly reduced. These results indicate that although in general spontaneously hypertensive rats respond normally to prostaglandin I2, in the kidney of spontaneously hypertensive rats the ability of prostaglandin I2 to attenuate angiotensin II-induced vasoconstriction is reduced. This selective renal defect may relate to the pathogenesis of high blood pressure in this genetic model of hypertension.
Hypertension 1993 Nov
PMID:Angiotensin II/prostaglandin I2 interactions in spontaneously hypertensive rats. 822 29

Preeclampsia is a pregnancy-specific condition of increased blood pressure accompanied by proteinuria, edema, or both. The incidence of preeclampsia has been reported as ranging from 2.5% to 7%. Risk factors for the development of preeclampsia include young maternal age, previous preeclampsia, twin pregnancy, chronic hypertension, diabetes mellitus, and hydatidiform mole. Vasospasm is considered central to the pathologic changes of preeclampsia, and the data suggest that this process is triggered by an imbalance between prostacyclin (prostaglandin I2) and thromboxane Ax, biologically active metabolites of arachidonic acid. Preeclampsia has a wide clinical spectrum ranging from mild to severe forms and, potentially, eclampsia with symptoms occurring primarily with severe disease. Preventive strategies under investigation include calcium supplementation and low-dose aspirin supplementation. Prenatal screening, monitoring, and management of preeclampsia are presented.
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PMID:Preeclampsia. 837 57

We have characterized angiotensin binding sites in cultured smooth muscle cells obtained from the aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. In both strains of rats the binding of 125I-angiotensin II (125I-Ang II) in smooth muscle cells was time dependent and reached a maximum at 60 minutes. Scatchard analysis revealed a single binding site in both strains with equilibrium constants (KD) of 5.35 nmol/L in SHR and 3.47 nmol/L in WKY rats. Binding capacities (Bmax) in smooth muscle cells averaged 270 and 150 fmol/mg protein in SHR and WKY rats, respectively. Angiotensin peptides competed for 125I-Ang II binding with an order of potency of Ang II > angiotensin-(1-7) = angiotensin I. In smooth muscle cells of the SHR, basal prostaglandin E2 (PGE2) and prostacyclin (prostaglandin I2 [PGI2]) release were threefold and 15-fold lower than that found in WKY rat smooth muscle cells. Ang II as well as angiotensin-(1-7) stimulated PGE2 and PGI2 release in WKY rat smooth muscle cells. In smooth muscle cells from SHR, Ang II increased the production of both PGE2 and PGI2, whereas angiotensin-(1-7) enhanced only PGE2 but not PGI2 release. There was no significant difference between Ang II-stimulated PGE2 and PGI2 release or angiotensin-(1-7)-stimulated PGE2 production in SHR and WKY rat smooth muscle cells. However, angiotensin-(1-7)-stimulated PGI2 release was significantly lower (p < 0.0005) in SHR compared with WKY smooth muscle cells. Collectively, the data suggest that smooth muscle cells of SHR contain a higher number of angiotensin binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Jun
PMID:Alterations in prostaglandin production in spontaneously hypertensive rat smooth muscle cells. 850 98

Ten dogs presenting mild chronic renal failure and hypertension after 27 months of uninephrectomy, during which they received a high sodium and high protein diet, were divided in two groups (n = 5) and followed for 15 months. The same diet was maintained and one of the groups received cicaprost treatment. The animals were periodically tested for biochemical and clinical parameters, and at months 0, 3, 6, and 15, glomerular filtration rate and renal plasma flow (RPF) were measured. Renal biopsies were made after 6 months of follow-up. Control group showed a higher thickening of pre- and intraglomerular portions of arteriolar vessels and an enhancement of mesangial matrix when compared with the treated group. Cicaprost also induced a significant elevation in RPF and a significant decrease in filtration fraction. All these findings suggest that cicaprost, an oral stable prostaglandin I2 analog, could have a protective renal effect in this experimental model.
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PMID:Cicaprost, a prostacyclin analog, protects renal function in uninephrectomized dogs in the absence of changes in blood pressure. 850 42

Bovine coronary arteries relax in response to bradykinin, methacholine, sodium nitroprusside, isoproterenol, and arachidonic acid in a concentration-dependent manner. The relaxations to methacholine, bradykinin, and arachidonic acid are lost when endothelium is removed. Indomethacin, a cyclooxygenase inhibitor, attenuated the relaxations to methacholine, bradykinin, and arachidonic acid and shifted the EC50 (control versus indomethacin) to each (1 x 10(-7) versus 3 x 10(-7) mo1/L, 3 x 10(-10) versus 2 x 10(-9) mo1/L, and 3 x 10(-7) versus 2 x 10(-6) mo1/L, respectively). Nitro-L-arginine, a nitric oxide synthase inhibitor, also attenuated the relaxations to methacholine, bradykinin, and arachidonic acid and shifted the EC50 (control versus nitro-L-arginine) to each (1 x 10(-7) versus 3 x 10(-7) mo1/L, 3 x 10(-10) versus > 10(-9) mo1/L, and 3 x 10(-7) versus > 10(-6) mo1/L, respectively). The combination of indomethacin and nitro-L-arginine blunted the relaxations to these agents and also shifted the EC50 values (control versus indomethacin plus nitro-L-arginine) to each (1 x 10(-7) versus 5 x 10(-7) mo1/L, 3 x 10(-10) versus > 10(-9) mo1/L, and 3 x 10(-7) versus > 10(-6) mo1/L, respectively). Methacholine, bradykinin, and arachidonic acid stimulated the release of prostaglandin I2, measured as 6-keto-PGF1 alpha. Indomethacin, but not nitro-L-arginine, inhibited arachidonic acid-induced release of 6-keto-PGF1 alpha. Vascular cGMP content was unchanged by arachidonic acid but was significantly elevated by bradykinin. Relaxations to prostaglandin I2 and sodium nitroprusside, but not 8,9-epoxyeicosatrienoic acid or isoproterenol, were inhibited by nitro-L-arginine. We conclude that the endothelium-dependent relaxations to methacholine, bradykinin, and arachidonic acid are partly due to prostaglandin I2 release. The remainder of the responses to these agents is due to the release of other relaxing factor or factors. Since bradykinin increased cGMP and nitro-L-arginine partially inhibited its relaxant effects, nitric oxide also appears to participate in the bradykinin-induced effect. Since the combination of indomethacin and nitro-L-arginine failed to completely block the relaxations to methacholine, bradykinin, and arachidonic acid, another endothelial factor must contribute to their vascular effects. Surprisingly, nitro-L-arginine attenuated the relaxations to arachidonic acid; however, L-arginine failed to reverse the effects of nitro-L-arginine on arachidonic acid-induced relaxations. In addition, arachidonic acid failed to increase cGMP. Nitro-L-arginine also reduced the responses to prostaglandin I2 and sodium nitroprusside. These data indicate that these arginine analogues may have effects other than competitive inhibition of nitric oxide synthase.
Hypertension 1996 Jul
PMID:Mediators of arachidonic acid-induced relaxation of bovine coronary artery. 867 67

Cellular calcium modulates enzyme activity, cell proliferation, and differentiation. In vascular smooth muscle cells (VSMC), calcium may contribute to increased vascular contractility and structural alterations in both hypertension and atherosclerosis. We investigated the role of calcium in angiotensin II (AII)-induced prostaglandin release and DNA synthesis in VSMC. Prostaglandin levels were determined by radioimmunoassay, and DNA synthesis was determined by the incorporation of [3H]thymidine. AII dose-dependently stimulated the release of prostaglandin E2 and prostaglandin I2, and this effect was synergistically enhanced by the Ca2+ ionophore A23187. Conversely, the AII response was inhibited by EGTA, a chelator of Ca2+ ions and by verapamil and nifedipine, two Ca2+ channel blockers or by incubation of the cells without exogenous Ca2+. TMB-8, an inhibitor of calcium mobilization, also strongly reduced angiotensin response. Similar results were obtained for angiotensin III (AIII) and vasopressin, two other agonists of prostaglandin production. AII- or serum-stimulated DNA synthesis was almost abolished by EGTA, whereas TMB-8, verapamil, and nifedipine had little or no effect. The production of prostaglandins triggered by angiotensins and vasopressin in VSMC is dependent on both intracellular and extracellular calcium, with calcium entering through L-type Ca2+ channels. Extracellular calcium is important for AII and serum mitogenic activity, but L-type Ca2+ channels do not appear to be implicated.
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PMID:Role of calcium in angiotensin II-induced prostaglandin release and DNA synthesis in rat vascular smooth muscle cells. 872 Apr 17

Recent studies have suggested that coronary endothelial cells produce and release nitric oxide (NO), prostaglandin I2, and epoxyeicosatrienoic acids (EETs). These endothelium-derived vasodilators play an important role in the control of coronary vascular tone. However, the mechanism by which these endothelium-derived vasodilators cause relaxation of coronary arterial smooth muscle has yet to be determined. This study characterized and compared the effects of NO, prostaglandin I2, and 11,12-EET on the two main types of potassium channels in small bovine coronary arterial smooth muscle: the large conductance Ca(2+)-activated K+ channels (KCa) and 4-aminopyridine-sensitive delayed rectifier K+ channels (Kdrf). In cell-attached patches, nonoate, an NO donor, activated both KCa and Kdrf channels. The open probability of both KCa and Kdrf channels increased 10- to 25-fold when nonoate was added to the bath at concentrations of 10(-6) to 10(-4) mol/L. 11,12-EET (10(-8) to 10(-4) mol/L) also increased the activity of the KCa channels in a concentration-dependent manner, but it had no effect on the activity of the Kdrf channels, even in the highest concentration studied (10(-4) mol/L). In contrast to the effect of 11,12-EET, iloprost, a prostaglandin I2 analogue (10(-6) to 10(-4) mol/L), produced a concentration-dependent increase in the activity of Kdrf channels without affecting the KCa channels. In conclusion, all three endothelium-derived vasodilators act to open potassium channels; however, the channel types that they affect are different. NO activates both KCa and Kdrf channels; 11,12-EET activates only the KCa channels; and prostaglandin I2 activates only the Kdrf channels.
Hypertension 1997 Jan
PMID:Regulation of potassium channels in coronary arterial smooth muscle by endothelium-derived vasodilators. 903 12

We reviewed the recent advances in the molecular characterization of prostanoid and bradykinin receptors. Prostanoids and bradykinin exert versatile actions in diverse tissues and cells through specific cell surface receptors. Molecular biological studies revealed the primary structure of eight types and subtypes of prostanoid receptors from various species. These include the thromboxane A2 receptor, prostacyclin receptor, prostaglandin (PG) F receptor, PGD receptor and four subtypes of PGE receptor (EP1, EP2, EP3 and EP4). There are four subtypes of bradykinin receptor (BK1, BK2, BK3 and BK4), but it is still unknown about the detail of BK3 and BK4. These results also have achieved the remarkable development in the field of human hypertension.
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PMID:[Prostaglandin and kallikrein-kinin systems]. 928 1

Cardiac fibroblasts, as the source of extracellular matrix for the left ventricle, subserve important functions to cardiac remodeling and fibrotic development following myocardial infarction or with pressure-overload cardiac hypertrophy. The fibroblast may be the target cell for angiotensin-converting enzyme inhibitors (ACEI) that are cardioprotective and reverse collagen deposition and remodeling but whose mechanisms of action remain controversial. Because we previously documented phenotypic differences between cardiac fibroblasts from the spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) left ventricle, the present study evaluated whether phenotypic differences also exist in the release of endogenous arachidonic acid metabolites or in the activation of phospholipase D, and the importance of observed differences to the formation of collagen and the mechanism of action of ACEI. The experimental design compared endogenous sources of arachidonic acid with exogenous prelabeling of cells. Angiotensin II stimulated greater arachidonic acid release than bradykinin, and WKY cells were more responsive than SHR. The major prostanoid formed by cardiac fibroblasts was prostaglandin I2 (PGI2), with more prostacyclin production by WKY cells than SHR cells both under nonstimulated conditions and in response to angiotensin II or bradykinin. Beraprost, a PGI2 analogue, was shown to decrease growth rate and DNA synthesis of fibroblasts and to inhibit mRNA expression for collagen types I and III, with SHR cells being less responsive to beraprost than WKY cells. These results potentially implicate eicosanoid metabolism, particularly PGI2, in collagen formation, fibrotic development, and cardiac remodeling, and they imply that the SHR genetic hypertension model may be predisposed to excess cardiac fibrosis.
Hypertension 1997 Nov
PMID:Prostacyclin release by rat cardiac fibroblasts: inhibition of collagen expression. 936 54


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