UMLS:C0020538 - FACTA Search

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

In the last few years, so many different substances produced by the endothelium have been discovered that this structure is considered today a paracrine organ. Among these substances, there are at least three with marked vascular effects: prostacyclin (PGI-2) and the endothelium-derived relaxing factor (EDRF) are vasodilators, platelet stabilizers and anti-atherogenic. On the other hand, endothelin-1 (ET-1) is a potent vasoconstrictor and probably pro-atherogenic. There are many agents that stimulate the liberation of these substances by the endothelium and most of them stimulate simultaneously the production of the three substances. Even though it is not possible yet to define the exact participation of the endothelium in the normal regulation of coronary blood flow it is highly probably that a disfunction of this structure secondary to hypercholesterolemia, hypertension, atheromatosis, diabetes and smoking may decrease the coronary reserve, induce coronary spasm and facilitates the development of atheroma.
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PMID:[Endothelium and coronary circulation]. 182 65

The mechanism of glucocorticoid-induced hypertension is not known. Although glucocorticoids can exert an inhibitory effect on prostaglandin synthesis in vitro, their in vivo influence on this system is controversial. The goal of the present study was to determine whether dexamethasone-induced hypertension in Wistar rats is due to inhibition of the synthesis of the vasodilator prostaglandin I2 (PGI2) in vivo. Dexamethasone caused a profound reduction (7 +/- 1 versus 21 +/- 5 ng per 24 h) in the urinary excretion of PGI-M (PGI-M), a major metabolite of PGI2, and a sustained rise in systolic arterial pressure which was maximal after 5 days (144 +/- 9 versus 103 +/- 3 mmHg). A study of the metabolism of [3H]-labeled 6-oxo-PGF1 alpha and PGI2 revealed that dexamethasone exerted a dual action on the prostaglandin system in vivo: an inhibition of PGI2 biosynthesis and an alteration of its metabolism, both effects contributing to the observed reduction in urinary levels of PGI-M. Exogenous arachidonic acid induced a fourfold increase in urinary PGI-M in normal rats (from 14 +/- 3 to 61 +/- 6 ng per 24 h). Despite a large decrease upon addition of dexamethasone, urinary PGI-M remained in the high-normal range in arachidonic acid-treated rats (21 +/- 8 ng per 24 h). Arachidonic acid exerted antihypertensive effects which were marginal initially but significant in the later phase of dexamethasone-induced hypertension (124 +/- 8 versus 139 +/- 8 mmHg in arachidonic acid-treated versus control rats after 7 days of dexamethasone).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostaglandin I2 and glucocorticoid-induced rise in arterial pressure in the rat. 250 53

Uterine prostacyclin synthase (PGI synthase) and prostaglandin endoperoxide synthase (PGH synthase) concentrations, measured by specific immunoradiometric assays, did not differ between patients with severe pregnancy-induced hypertension (syn. pre-eclampsia; n = 5) and normotensive gravidae (n = 6) with comparable gestational ages (34 - 38 weeks). Myometrial microsomes from pre-eclamptic women contained ten times more PGI synthase than PGH synthase and the ratio of PGI synthase to PGH synthase (mean +/- SD; 10.1 +/- 3.9) was not different from that in normotensive pregnancies. None of the pre-eclamptic patients had myometrial enzyme levels that were more than one standard deviation below the mean established previously for pregnancies ranging from 32 to 42 weeks of gestation. These findings indicate that the commonly observed association between deficient PGI2 production and pregnancy-induced hypertension cannot be explained in terms of a generalized lack of immunoassayable prostacyclin or prostaglandin endoperoxide synthases.
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PMID:Control of prostacyclin synthesis in pregnancy-induced hypertension. 392 69

Prostaglandins participate in the pathophysiology of septic shock; however, their exact role is unclear. In this study we investigated the possibility that thromboxane and prostacyclin, the most recently discovered prostaglandins, may be related to the pulmonary arterial hypertension (thromboxane) and systemic arterial hypotension (prostacyclin) during endotoxin shock in the baboon. There are no previously reported studies in the subhuman primate. In this study ten male baboons received an LD70 dose of E. coli endotoxin. Cardiac output, mean systemic arterial pressure, pulmonary arterial pressure, blood gases, WBC and platelet counts, and prostaglandins were determined at 0, 15, 60, 120, 180, and 240 minutes. Thromboxane and prostacyclin levels were significantly (P less than 0.05) increased after the endotoxin injection. Systemic arterial PGI values increased within 15 minutes, peaked at two hours, and was directly related to the fall in systemic arterial pressure (r = 0.93). In contrast, thromboxane values peaked at 15 minutes and directly related (r = 0.90) to the rise in pulmonary artery pressure. Thromboxane and prostacyclin are significantly increased in subhuman primate endotoxin shock. The temporal relationship of thromboxane and pulmonary arterial pressure suggests that thromboxane may mediate the effects of endotoxin on the pulmonary vasculature.
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PMID:Thromboxane, prostacyclin, and hemodynamic events in primate endotoxin shock. 703 16

There is a correlation between circulating insulin levels and blood pressure over a wide range of insulin levels and in a variety of clinical conditions. Production of prostaglandin (PG)E(2) (PGE(2)) and prostacyclin (PGI(2)), two potent vasodilators, by adipose tissue is increased in severe insulin deficiency, eg, diabetic ketoacidosis (DKA), explaining the decreased peripheral vascular resistance in DKA. Conversely, decreased production of PGE(2) and PGI(2) may mediate the relationship between hyperinsulinemia and hypertension. Although insulin inhibits PG production in normal rat adipose tissue, PG production in adipose tissue from patients or experimental animals with nonketotic diabetes mellitus (DM) and DKA has not been studied. We examined the effect of plasma insulin levels on blood pressure and on adipose tissue PG production in rats with DM and DKA and normal rats. There was a significant relationship between plasma insulin level and blood pressure in rats with DM and normal controls (P < .021) and in rats with DKA and normal controls (P < .0001). There was an inverse linear correlation between plasma insulin levels and basal 6-keto-PGF(1 alpha) production by a mixture of adipocytes and endothelial cells from epididymal adipose tissue in rats with DKA and normal rats (P < .0252, R2 = .67). Rates of basal glycerol, PGE(2), and 6-keto-PGF(1alpha) production by a mixture of adipocytes and endothelial cells from epididymal adipose tissue were significantly higher in rats with DKA than in normal rats. These rates were also higher in rats with DM than in normal rats, but only glycerol values were statistically significant. In rats with DM, PGE(2) production induced by epinephrine 2 x 10(-5) mol/L (but not lower concentrations) was significantly greater than basal production (P < .05); production of 6-keto-PGF(1alpha) was not stimulated. In rats with DKA, 6-keto-PGF(1alpha) production induced by epinephrine 2 x 10(-5) mol/L (but not lower concentrations) was significantly greater than basal production (P < .05); production of PGE(2) was not stimulated. We conclude the following: (1) there is a close correlation between circulating insulin level and systemic blood pressure when rats with DM and DKA are compared with controls; (2) in insulin deficiency, PGI(2) and PGE(2) production are increased in adipose tissue versus normal tissue; and (3) the correlation between insulin level and blood pressure may be mediated by the inhibitory effect of insulin on vasodilative PG production by adipose tissue.
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PMID:The relationship between plasma insulin level, prostaglandin production by adipose tissue, and blood pressure in normal rats and rats with diabetes mellitus and diabetic ketoacidosis. 863 42

The angiotensin subtype-1 (AT(1)) receptor mediates renal prostaglandin E(2) (PGE(2)) production, and pharmacological blockade of the angiotensin subtype-2 (AT(2)) receptor potentiates the action of angiotensin II (Ang II) to increase PGE(2) levels. We investigated the role of the AT(2) receptor in prostaglandin metabolism in mice with targeted deletion of the AT(2) receptor gene. Mice lacking the AT(2) receptor (AT(2)-null) had normal blood pressure that was slightly elevated compared with that of wild-type (WT) control mice. AT(2)-null mice had higher renal interstitial fluid (RIF) 6-keto-PGF(1alpha) (a stable hydrolysis product of prostacyclin [PGI(2)]) and PGE(2) levels than did WT mice, and had similar increases in PGE(2) and 6-keto-PGF(1alpha) in response to dietary sodium restriction and Ang II infusion. In contrast, AT(2)-null mice had lower PGF(2alpha) levels compared with WT mice during basal conditions and in response to dietary sodium restriction or infusion of Ang II. RIF cAMP was markedly higher in AT(2)-null mice than in WT mice, both during basal conditions and during sodium restriction or Ang II infusion. AT(1) receptor blockade with losartan decreased PGE(2), PGI(2), and cAMP to levels observed in WT mice. To determine whether increased vasodilator prostanoids prevented hypertension in AT(2)-null mice, we treated AT(2)-null and WT mice with indomethacin for 14 days. PGI(2), PGE(2), and cAMP were markedly decreased in both WT and AT(2)-null mice. Blood pressure increased to hypertensive levels in AT(2)-null mice but was unchanged in WT. These results demonstrate that in the absence of the AT(2) receptor, increased vasodilator prostanoids protect against the development of hypertension.
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PMID:Increased renal vasodilator prostanoids prevent hypertension in mice lacking the angiotensin subtype-2 receptor. 1041 47

The protective effect of vasodilator agents linked to the cAMP pathway is less effective for buffering the vasoconstrictor effect of angiotensin II in young animals with genetic hypertension. To determine the underlying cellular mechanism, experiments were performed on freshly isolated preglomerular resistance arterioles obtained from kidneys of 7-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Specific high-affinity saturable binding of (3)H-prostaglandin (PG) E(2) revealed 1 receptor class in renal microvessels; PGE(2) receptor density was similar in SHR and WKY (106 versus 115 fmol/mg; P>0.8), as was receptor affinity (3.6 versus 3.5 nmol/L; P>0.7). Basal cAMP activity was similar in renal arterioles from SHR and WKY. A major finding was that PGE(2), PGI(2), and isoproterenol produced weaker stimulation of cAMP formation in arteriolar cells of SHR (P<0.02). In contrast, GTPgammas and forskolin stimulated cAMP generation to a similar degree in both rat strains, which suggests normal adenylate cyclase activity in hypertension-prone SHR. Immunoblots revealed the presence of 3 classes of G proteins (G(s), G(i), and G(q)) in preglomerular arterioles. The relative amounts of discernible G-protein alpha-subunits in renal resistance vessels did not differ between SHR and WKY. These results extend previous in vivo studies of abnormal renal vascular reactivity in SHR and more directly localize defective coupling of the prostaglandin and beta-adrenergic receptors to a stimulatory G protein and cAMP production in freshly isolated preglomerular arteriolar cells of young SHR. This dysfunction may be due to an abnormal interaction between prostaglandin receptors and G(s) protein that leads to inefficient coupling of initiating steps in the cAMP-protein kinase A cascade during the development of hypertension.
Hypertension 1999 Nov
PMID:Impaired prostaglandin E(2)/prostaglandin I(2) receptor-G(s) protein interactions in isolated renal resistance arterioles of spontaneously hypertensive rats. 1056 95

1. Chronic inhibition of nitric oxide synthase (NOS) provokes a hypertensive state which has been shown to be angiotensin II (Ang-II) dependent. In addition to raising blood pressure, NOS inhibition also causes leukocyte adhesion. The present study was designed to define the role of Ang-II in hypertension and in the leukocyte-endothelial cell interactions induced by acute NOS or cyclo-oxygenase (COX) inhibition using intravital microscopy within the rat mesenteric microcirculation. 2. While pretreatment with an Ang-II AT(1) receptor antagonist (losartan) reversed the prompt increase in mean arterial blood pressure (MABP) caused by indomethacin, it had no effect on the increase evoked by systemic L-NAME administration. 3. Pretreatment with losartan inhibited the leukocyte rolling flux, adhesion and emigration which occurs after 60 min NOS inhibition by 83, 80 and 70% respectively, and returned leukocyte rolling velocity to basal levels. 4. Losartan significantly reduced the leukocyte-endothelial cell interaction elicited by COX inhibition. In contrast, leukocyte recruitment induced by acute mast cell activation was not inhibited by losartan. 5. AT(1) receptor blockade also prevented the drop in haemodynamic parameters such as mean red blood cell velocity (V(mean)) and shear rate caused by NOS and COX inhibition. 6. In this study, we have demonstrated a clear role for Ang-II in the leukocyte-endothelial cell interactions and haemodynamic changes which arise in the absence of NO or prostacyclin (PGI(2)). This is of interest since leukocyte recruitment, which culminates in the vascular lesions that occur in hypertension, atherosclerosis and myocardial ischemia-reperfusion injury, might be prevented using AT(1) Ang-II receptor antagonists.
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PMID:Angiotensin II is involved in nitric oxide synthase and cyclo-oxygenase inhibition-induced leukocyte-endothelial cell interactions in vivo. 1115 20

Nitric oxide (NO) has been identified as an effective vascular relaxant. This study analyses the contribution of the precursor L-arginine (L-arg) by oral administration in two kidney-two clip hypertension in the rat (2K-2C). Two groups were studied: sham (SH, n=21) and hypertensive (HT, n=15). After 4 weeks of surgery, a group of rats remained as controls (SHc and HTc, respectively), while others were supplemented with L-arg (1.25 g/L) in drinking water (SHa and HTa) for 3 weeks. Blood pressure was significantly increased in 2K-2C rats but remained unchanged after L-arg treatment. Plasma nitrite/nitrate concentrations were not different among groups. The contractile response of aorta to KCl, serotonin and the protein kinase C (PKC) stimulant, phorbol 12,13-dibutyrate (PDBu) was also evaluated. Higher contractile responses to PDBu (p<0.001) and lower relaxation to acetylcholine (Ach 10(-6) M, p<0.05 and 10(-5)M, p<0.02) were observed in aortic rings of HTc vs SHc; L-arg supplementation significantly diminished tension development to all agonists (p<0.05) but failed to modify the lower relaxation to Ach in HTa. Thromboxane (TxA(2)) - synthesis in rings of HTc was higher than in SHc under basal conditions (p<0.05). In the groups with supplement of L-arg, PDBu significantly stimulated prostacyclin (PGI(2)) synthesis more in HTa rats than in SHa ones (p<0.05). To conclude: 1) L-arg fails to modify hypertension development in 2K-2C rats; and 2) L-arg exerts a beneficial effect on the vascular wall, by reducing contractility in rings from HTa rats; it also improved PGI(2) synthesis under PDBu stimulation. 3) greater PKC activation and TxA(2) production rather than lower NO availability might result in systemic hypertension in 2K-2C rats.
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PMID:Effect of oral L-arginine administration for three weeks in two kidney-two clip hypertensive rats. 1126 99

Obese hypertensives have increased nonesterified fatty acids (NEFAs) and alpha-adrenergic vascular reactivity. Raising NEFAs locally with intralipid and heparin augments dorsal hand venoconstrictor responses to phenylephrine, an alpha(1)-adrenoceptor agonist. The enhanced venoconstrictor responses were reversed by indomethacin. The findings suggest that raising NEFAs leads to the generation of cyclooxygenase (COX) product(s) that enhance vascular reactivity. To test this notion, 6-keto-PGF(1alpha) and TxB(2), the stable metabolites of prostaglandin H(2) (PGH(2)); prostacyclin (PGI(2)); and thromboxane (TxA(2)), were measured approximately 1.5 to 2 cm downstream of a dorsal hand vein infusion of intralipid and heparin (n=10) or saline and heparin (n=5) for 2 hours each. During the third hour, intralipid and heparin (experimental) and saline and heparin (control) were continued, and either saline (control) or indomethacin (intervention) were infused. Intralipid and heparin raised local 6-keto PGF(1alpha) concentrations by 350% to 500% (P<0.005), but saline and heparin did not (P=NS). TxB(2) levels did not change significantly with any infusion. Infusion of indomethacin during the third hour of intralipid and heparin lowered plasma 6-keto-PGF(1alpha) (P<0.05), whereas infusion of saline with intralipid and heparin did not (P=NS). Oleic and linoleic acids at 100 micromol/L, increased 6-keto-PGF(1alpha) in vascular smooth muscle cells (VSMCs) through a protein kinase C and extracellular, signal-regulated kinase independent pathway. However, oleic and linoleic acids increased intracellular Ca(2+) in VSMCs. The data indicate that NEFAs induce the production of COX products, perhaps via Ca(2+)-dependent activation of phospholipase A(2). The COX product(s) may contribute to increased vascular alpha-adrenergic reactivity among insulin-resistant individuals when NEFAs are elevated.
Hypertension 2001 Oct
PMID:Lipids stimulate the production of 6-keto-prostaglandin f(1alpha) in human dorsal hand veins. 1164 Dec 99

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