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

The role of platelets in lung injury has not been well defined. In the present study of isolated perfused rat lungs, phorbol myristate acetate (PMA; 0.15 microgram/ml) or platelets (6.7 X 10(4)/ml) alone did not discernibly change the pulmonary arterial pressure (PAP) or lung weight (LW). However, the combination of platelets and PMA drastically increased the PAP and LW (delta PAP 26.2 +/- 1.0 mmHg, delta LW 2.7 +/- 0.4 g). delta PAP was positively correlated with the increase in thromboxane B2 produced by infusion of platelets and PMA (thromboxane B2 = 35.6 + 0.97 delta PAP, r = 0.67, P less than 0.01). The hypertension and edema formation induced by PMA and platelets were strongly attenuated by indomethacin, an inhibitor of platelet cyclooxygenase (delta PAP 5.6 +/- 2.0 mmHg, P less than 0.001; delta LW 0.0 +/- 0.1 g, P less than 0.001), and by imidazole, an inhibitor of thromboxane A2 synthase (PAP 8.0 +/- 2.5 mmHg, P less than 0.001; LW 0.0 +/- 0.3 g, P less than 0.01). Inactivation of platelet lipoxygenase with nordihydroguaiaretic acid mildly depressed pulmonary pressure but did not affect delta LW (delta PAP 18.9 +/- 1.6 mmHg, P less than 0.05; delta LW 3.1 +/- 0.3 g, P greater than 0.05). In vitro experiments showed that the capacity of platelets to release oxygen radicals was only 2.6% of that found for granulocytes. These results suggest that platelets may be activated by PMA to increase PAP and vascular permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclooxygenase pathway mediates lung injury induced by phorbol and platelets. 190 12

Arachidonic acid (AA) can be metabolized to an array of products affecting biological mechanisms such as those governing vascular reactivity and transport function. Metabolism of AA by cyclooxygenase in the nephron is discretely localized and is overshadowed in some nephron segments by a considerable capacity to generate P-450 AA metabolites. The synthesis of renal P-450 AA products is increased in hypertension. AA metabolites participate in fluid and electrolyte homeostasis and regulation of tissue blood flow and act as modulators of pressor systems. In addition, eicosanoids either augment or mediate the vasodilator-diuretic actions of the kallikrein-kinin system.
Hypertension 1991 Nov
PMID:Arachidonate metabolites and kinins in blood pressure regulation. 193 79

As a source of several vasoactive factors, the endothelium takes part in the regulation of vascular tone. The most important endothelium-derived vasoactive substances are nitric oxide, prostacyclin, endothelin-1 and contracting factors requiring the activity of cyclooxygenase. The endothelium is an obvious target organ of cardiovascular risk factors. Accordingly, functional alterations do occur with aging, hypertension, and lipids. All three conditions are associated with a decreased basal and stimulated release of endothelium-derived nitric oxide. On the other hand, the release of endothelin-1 appears to increase with age, while the sensitivity to the peptide markedly decreases under the same conditions. In the spontaneously hypertensive rat, acetylcholine and stretch evoke the release of cyclooxygenase-dependent endothelium-derived contracting factor, most likely prostaglandin H2. The sensitivity and circulating levels of endothelin-1, on the other hand, are reduced in this experimental model of hypertension. In the porcine coronary circulation, oxidized low-density lipoproteins selectively reduce endothelium-dependent relaxations to aggregating platelets, serotonin, and thrombin which are mediated by nitric oxide. The alterations of endothelial function occurring with aging, hypertension, and hyperlipidemia may have important clinical implications for the pathogenesis of cardiovascular disease.
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PMID:Endothelium-dependent control of vascular tone: effects of age, hypertension and lipids. 195 6

Production of some lipoxygenase and cyclooxygenase derivatives of arachidonic acid was measured in placental tissue obtained from women with gestational hypertension and with normal pregnancies. The levels of leukotriene B4 were about five times higher in placentas from hypertensive women and also raised thromboxane A2 and reduced prostaglandin E2 levels were observed. Prostacyclin production was lowered only in women with more severe hypertension, in association with the highest measured levels of leukotriene B4 and thromboxane A2. It is suggested that increased placental levels of leukotriene B4 and thromboxane A2 appear already in mild gestational hypertension, while depression of prostacyclin may occur only at more severe stages of gestational hypertensive disease.
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PMID:Increased placental production of leukotriene B4 in gestational hypertension. 196 52

The majority of cases of impotence are associated with vascular risk factors such as diabetes, hypercholesterolemia, hypertension and smoking. These factors induce impairment of endothelium-dependent relaxation of blood vessels in man and in experimental animals. In this study the effects of hypercholesterolemia on the reactivity of rabbit corpus cavernosum smooth muscle strips to endothelium-dependent and endothelium-independent agents were investigated. New Zealand White rabbits (n = 14) were randomly divided into control and treatment groups. The control group (n = 7) received a regular diet while the treatment group (n = 7) was fed a diet of 0.5% cholesterol and 4% peanut oil for 10 weeks. Animals were then sacrificed and the corporal tissue studied in organ chambers for isometric tension measurement. Tissue was contracted with phenylephrine and concentration-dependent relaxation to acetylcholine, in the presence and absence of indomethacin, and to nitroprusside were examined. Blood level of cholesterol in the cholesterol-fed group was significantly higher compared to the control group. Contractions to phenylephrine were similar in both groups. Hypercholesterolemia, however, inhibited relaxation to acetylcholine but did not alter relaxation to nitroprusside, a cyclic guanosine monophosphate (cGMP)-dependent, direct smooth muscle dilator. Indomethacin enhanced the relaxations to acetylcholine in both control and cholesterol-fed groups but did not correct the difference in the relaxation to acetylcholine between both groups. It is concluded that hypercholesterolemia impairs endothelium-mediated relaxation of rabbit corpus cavernosum smooth muscle. The mechanism for the endothelial dysfunction does not appear to involve alteration in cyclooxygenase products of arachidonate or the cGMP-dependent relaxation of corporal smooth muscle. Impairment of endothelium-dependent relaxation of corporal smooth muscle may contribute to the pathophysiology of impotence associated with hypercholesterolemia in man.
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PMID:Hypercholesterolemia impairs endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle. 205 97

Endothelial cells modulate vascular tone by releasing endothelium-derived relaxing (EDRF) and contracting factors. An imbalance of these factors in hypertension could contribute to increased peripheral vascular resistance. Mesenteric resistance arteries of Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) were suspended in a myograph filled with physiological salt solution (37 degrees C; 95% O2-5% CO2). In WKY rings contracted with norepinephrine, acetylcholine (10(-9)-10(-4) M) evoked endothelium-dependent relaxations (88 +/- 2%, IC50 7.3 +/- 0.1; n = 31). Hemoglobin (10(-5) M) but not meclofenamate (10(-5) M) reversed the relaxations delineating EDRF as the mediator. Nitric oxide (3 X 10(-9)-10(-5) M) induced comparable relaxations as acetylcholine. In SHRSP, relaxations to acetylcholine but not those to nitric oxide were impaired (61 +/- 5%, IC50 greater than 6.6 +/- 0.4; n = 24; P less than 0.005). In SHRSP, meclofenamate but not the thromboxane synthetase inhibitor CGS 13080 normalized endothelium-dependent relaxations. Relaxations to sodium nitroprusside were enhanced in SHRSP both in rings with and without endothelium. Thus our results are compatible with the concept that endothelium-dependent relaxations in resistance arteries are mediated by nitric oxide. In SHRSP, endothelium-dependent relaxations are impaired because of a cyclooxygenase-dependent substance interfering with the release and/or action of EDRF.
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PMID:Impaired endothelium-dependent relaxations in hypertensive resistance arteries involve cyclooxygenase pathway. 210 97

Low doses of Escherichia coli hemolysin cause thromboxane-mediated hypertension and vascular leakage in blood-free perfused rabbit lungs (W. Seeger, H. Walter, N. Suttorp, M. Muhly, and S. Bhakdi, J. Clin. Invest. 84:220-227, 1989). The recirculating buffer medium and bronchoalveolar lavage fluid from lungs exposed to hemolysin (2.5 hemolytic units per ml) in the presence of cyclooxygenase inhibitor were analyzed for leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) by reverse-phase and straight-phase high-pressure liquid chromatographic techniques combined with UV spectrum analysis and post-high-pressure liquid chromatography radioimmunoassay. A rapid release of large amounts of cysteinyl-LTs and leukotriene B4 (LTB4) into the intravascular space was noted (total sum, approximately 4 to 5 micrograms). Similar quantities have hitherto been elicited only by high concentrations of the artificial calcium ionophore A 23187. Moreover, a marked liberation of 5-HETE and 12-hydroxyheptadecatrienoic acid into the buffer medium occurred, whereas LTB4 represented the predominant compound in the lavage fluid. The hemolysin-induced burst of LT and HETE generation preceded the onset of vascular leakage. The outstanding capacity of E. coli hemolysin to produce the liberation of potent lipid mediators is probably relevant to the pathways of vascular injury and amplification of inflammatory events during severe infection with hemolytic E. coli strains.
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PMID:Leukotriene and hydroxyeicosatetraenoic acid generation elicited by low doses of Escherichia coli hemolysin in rabbit lungs. 211 26

Characterization of the PGI2 producing enzyme system (P.E.S.) in pregnancy induced hypertension (PIH) was carried out by comparing its conversion from arachidonic acid (A.A.) or PGH2 to PGI2 using enzyme preparations from endothelial cells of the umbilical vein in normal pregnancy (N) and mild (M) and severe (S) types of PIH. 1) The conversion rate from A.A. to PGI2 in N was significantly (p less than 0.05) higher than in M and S. 2) The conversion rate from PGH2 to PGI2 in N was higher than in M and that in M was higher than in S. 3) The apparent Vmax values (nM/mg protein) (mean +/- S.E.M.) for P.E.S. in N (0.88 +/- 0.21) were significantly (p less than 0.05) lower than in M (2.76 +/- 0.71) and S (1.63 +/- 0.18). The apparent Km values (microM) (mean +/- S.E.M.) for P.E.S. in N (0.76 +/- 0.25) were significantly (p less than 0.05) higher than in M (0.29 +/- 0.07) and significantly (p less than 0.05) lower than in S (3.26 +/- 0.78). 4) The apparent Vmax values for PGI2 synthetase (P.S.) in N (0.44 +/- 0.09) and M (0.61 +/- 0.10) were significantly (p less than 0.05) higher than in S (0.11 +/- 0.06). The apparent Km values for P.S. in N, M and S were 0.12 +/- 0.07, 0.13 +/- 0.06 and 0.16 +/- 0.04, respectively. The present study showed that the symptoms in M may be kept from becoming aggravated by the production of large amounts of PGI2, due mainly to activation of cyclooxygenase, whereas progressive disorder of the regulation of blood pressure in S may be caused by low production of PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Significance of the PGI2 producing enzyme system in the pathogenesis of pregnancy-induced hypertension]. 212 Mar 73

The goal of this study was to determine whether responses of the basilar artery are altered during chronic hypertension. We measured the diameter of the basilar artery using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Acetylcholine (10 microM) dilated the basilar artery by 25 +/- 4% (means +/- SE) in WKY but by only 2 +/- 2% in SHR. Bradykinin (1.0 microM) dilated the basilar artery by 12 +/- 1% in WKY, but did not alter diameter in SHR (-0.1 +/- 2%). In contrast, nitroglycerin produced similar vasodilatation in WKY and SHR. Next, we examined the possibility that impaired vasodilatation in SHR may be related to the production of a cyclooxygenase constrictor substance. Indomethacin (10 mg/kg iv) did not restore vasodilatation in response to acetylcholine and bradykinin in SHR. Finally, we examined the role of nitric oxide in dilatation of the basilar artery in response to acetylcholine and bradykinin in WKY. NG-Monomethyl-L-arginine (L-NMMA; 1.0 microM) had little effect on baseline diameter but inhibited vasodilation in response to acetylcholine and bradykinin. Vasodilatation in response to nitroglycerin was not altered by L-NMMA. These findings suggest a profound impairment of endothelium-dependent dilatation of the basilar artery during chronic hypertension. In addition, impaired vasodilatation is not related to the production of a cyclooxygenase constrictor substance. Furthermore, dilatation of the basilar artery in WKY in response to acetylcholine and bradykinin appears to be related to the production of nitric oxide or a substance capable of liberating nitric oxide.
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PMID:Impairment of endothelium-dependent dilatation of basilar artery during chronic hypertension. 212 45

Eicosanoids, especially prostaglandins and other arachidonic acid metabolites, play an important role in gestosis. Experimental and clinical evidence suggest prostacyclin deficiency, enhanced platelet reactivity and increased production of thromboxane A2 as possible reasons for gestosis. In addition, pathological interactions between cyclooxygenase-derived products and the renin-angiotensin- and kallikrein-kinin systems may exist and contribute to hypertension and reduced fetoplacental blood flow. Moreover, pregnancy-induced hypertension appears to be also related to lipoxygenase products and enhanced lipid peroxidation. In general, little is known about the regulation of arachidonic acid metabolism in gestosis. It is also unknown whether altered activities of mediators and hormones are cause or effect of pregnancy-induced hypertension. This is particularly relevant to the site of eicosanoid formation, i.e. platelets, the trophoblast or endothelial cells. At this time, it is not possible to give therapeutical recommendations, which are specifically designed to correct changes in eicosanoid production in gestosis. Antihypertensive therapy alone is insufficient, particularly with regard to the fetal situation. Preventive treatment with low-dose acetylsalicylic acid may have a protective effect against pregnancy-induced hypertension. Presently, more selective antagonists of thromboxane generation and/or action are being developed and might provide fresh insights both into the pathology of the disease and improved drug treatment.
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PMID:[The significance of eicosanoids in gestosis]. 212 6


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