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

This study investigated the release of prostacyclin (PGI2) and thromboxane A2 (TXA2) from the aortic walls of various experimental hypertensive rats, e.g. spontaneously hypertensive rats (SHR), Dahl salt-sensitive (Dahl S) rats, deoxycorticosterone (DOCA)-salt hypertensive rats and renovascular (2-kidney, 1-clip (2K1C) and 1-kidney, 1-clip (1K1C] hypertensive rats. The PGI2 generation was increased significantly in these hypertensive models, irrespective of the hypertensive mechanisms, when they developed established hypertension. Dahl S rats, having an impaired PGI2 production on a low salt diet, restored PGI2 generating capacity to the control level of Dahl salt-resistant rats when they were fed a high salt diet and developed salt-induced hypertension. On the other hand, the TXA2 generation in the vascular walls was enhanced particularly in rat models for genetic hypertension, and this system was unaltered in the models for secondary hypertension, e.g. DOCA-salt and renovascular hypertension. Thus, it is suggested that the elevation of blood pressure is associated with an increase in vascular PGI2 production, and that the increased vascular TXA2 production is a characteristic feature of genetic hypertension.
 ...
PMID:Vascular eicosanoid production in experimental hypertensive rats with different mechanisms. 187 Nov 82

Key discoveries in the past decade revealed that the endothelium can modulate the tone of underlying vascular smooth muscle by the synthesis/release of potent vasorelaxant (endothelium-derived relaxing factors; EDRF) and vasoconstrictor substances (endothelium-derived contracting factors; EDCF). It has become evident that the synthesis and release of these substances contribute to the multitude of physiological functions the vascular endothelium performs. Accumulating evidence suggests that at least one of the EDRFs is identical with nitric oxide (NO) or a labile nitroso compound, which is produced from L-arginine by an NADPH- and Ca(2+)-dependent enzyme, arginine oxidase. The existence of more than one chemically distinct EDRF has been proposed, including an endothelium-derived hyperpolarizing factor (EDHF). The target of EDRF (NO) is soluble guanylate cyclase (increase in cyclic GMP) while EDHF appears to activate a K(+)-channel in vascular smooth muscle. Recent data suggest that muscarinic receptor subtypes selectively mediate the release of EDRF(NO) (M2) and EDHF (M1). EDRF(NO) affects not only the underlying vascular smooth muscle, but also platelets, inhibiting their aggregation and adhesion to the endothelium. The antiaggregatory effect of EDRF is synergistic with prostacyclin, so their combined release may represent a physiological mechanism aimed at preventing thrombus formation. An additional proposed biological function of EDRF(NO) is cytoprotection by virtue of scavenging superoxide radicals. The endothelium can also mediate vasoconstriction by the release of a variety of endothelium-derived contracting factors (EDCF). Other than the unique peptide endothelin, the nature of EDCFs has not yet been firmly established. Autoregulation of cerebral and renal blood flow and hypoxic pulmonary vasoconstriction may represent the physiological role of endothelium-dependent vasoconstriction. Growing evidence indicates that the endothelium can serve as a unique mechanoreceptor, sensing and transducing physical stimuli (e.g., shear forces, pressure) into changes in vascular tone by the release of EDRFs or EDCFs. In physiological states, a delicate balance exists between endothelium-derived vasodilators and vasoconstrictors. Alterations in this balance can result in local (vasospasm) and generalized (hypertension) increase in vascular tone and also in facilitated thrombus formation. Endothelial dysfunction may also contribute to the pathophysiology of angiopathies associated with hypercholesterolemia and atherosclerosis.
 ...
PMID:Endothelium-derived relaxing and contracting factors. 187 96

Placentae from pregnancies complicated by pregnancy-induced hypertension (PIH) secrete significantly more 15-hydroxyeicosatetraenoic acid (15-HETE) than gestation-matched controls. 15-HETE and its hydroperoxy precursor can inhibit prostacyclin biosynthesis and may thus contribute to the pathological sequelae of PIH.
 ...
PMID:Increased production of 15-hydroxyeicosatetraenoic acid by placentae from pregnancies complicated by pregnancy-induced hypertension. 188 43

High blood pressure (BP) complicates approximately 10% of all pregnancies. Hypertension in pregnancy falls into four categories: (1) preeclampsia-eclampsia, (2) chronic hypertension of whatever cause, (3) preeclampsia-eclampsia superimposed to chronic hypertension or renal disease, and (4) transient or late hypertension (gestational hypertension). Preeclampsia, the association of hypertension, proteinuria, and edema, accounts for more than 50% of all the hypertensive disorders of pregnancy and is a major cause of fetal and maternal morbidity and mortality. Unfortunately, distinguishing between preeclampsia and other causes of hypertension on clinical grounds can be difficult because of the lack of specific tests for differential diagnosis. Increased vascular resistance has been claimed as the primary cause of preeclampsia; however, a variable hemodynamic profile with relatively high cardiac outputs, normal filling pressures, and inappropriately high systemic vascular resistances is now reported by most investigators. Imbalance between vasodilator and vasoconstrictor eicosanoids may account for platelet activation and increased responsiveness to pressor peptides. Altered prostacyclin (PGI2) to thromboxane A2 (TxA2) ratio in maternal uteroplacental vascular bed may favor local platelet activation and vasoconstriction contributing to placental insufficiency and fetal distress. Alternatively, recent evidence seems to suggest that fetal umbilical placental circulation may be the site of the primary vascular injury. Whether low-dose aspirin prevents preeclampsia because it inhibits the excessive maternal TxA2 or whether the partial inhibition of fetal TxA2 is also of therapeutic value remains to be established. Treatment of severe hypertension in pregnancy is probably important to prevent cardiac failure or cerebrovascular accidents in the mother. The need for pharmacological therapy of mild to moderate hypertension is still debated, since no formal studies are available to clarify whether pharmacological treatment in such instances effectively reduces maternal or fetal risk. For the treatment of preeclampsia, hydralazine and nifedipine may be used when delivery is not applicable. Labetalol and diazoxide are effective for hypertensive emergencies. Life-threatening hypertension that does not respond to more conventional therapy is an indication for the use of sodium nitroprusside. For chronic hypertension, alpha-methyldopa remains the treatment of choice; if ineffective, hydralazine or beta-blockers are suitable. Effectiveness and safety of other molecules remain elusive.
 ...
PMID:Prevention and treatment of pregnancy-associated hypertension: what have we learned in the last 10 years? 188 20

1. Given the unexplained frequent association between systemic hypertension and obstructive sleep apnoea (OSA), the secretion of prostanoids during sleep was investigated (more specifically, the ratio of prostacyclin (PGI2) to thromboxane A2 (TxA2), since they have marked opposite effects on vascular tone). Prostacyclin has vasodilating effects, whereas thromboxane results in vasoconstriction. 2. In 11 OSA drug-free male patients (age 53 +/- 2 years, mean +/- s.e.m.; apnoea index 55 +/- 15 apnoeas/hour of sleep; body mass index 31 +/- 2 kg/m2), we measured the urinary excretion during sleep of 6-keto-PGF1-alpha and of thromboxane TxB2 (the stable metabolites of prostacyclin PGI2 and of thromboxane A2 respectively). This was done on two consecutive nights; one untreated, the other with nasal continuous positive airway pressure (CPAP) treatment. The results were compared with those of nine normal unobese male subjects. 3. The urinary ratio of 6-keto-PGF1-alpha to TxB2 was significantly (P less than 0.001) lower in the untreated OSA patients (1.7 +/- 0.2) than in the controls (3.1 +/- 0.3). It significantly increased with CPAP treatment to 2.3 +/- 0.2, P less than 0.02, which was no longer different from the controls. 4. These results suggest that OSA is associated with an abnormal release of prostanoids during sleep resulting in a decrease of the prostacyclin to thromboxane ratio which potentially has a vasoconstricting effect. The relationship between these changes and the systemic hypertension often observed in OSA patients remains to be established.
 ...
PMID:Urinary excretion of prostanoids during sleep in obstructive sleep apnoea patients. 191 53

Prostacyclin (PGI2) synthase is one of the key enzymes for vasodepressor PGI2 biosynthesis in the vascular wall. In this study, we attempted to define the alterations in PGI2 synthase and its role in the PGI2 generation in the vascular wall of deoxycorticosterone acetate (DOCA)-salt rats. The PGI2-generating capacity was enhanced significantly when DOCA-salt rats established hypertension, whereas the generation of other arachidonate metabolites, eg, PGE2, PGF2 alpha, and thromboxane, was unaltered. Moreover, the increase in PGI2 generation was associated with an increase in PGI2 synthase activity in the vascular wall. Indeed, the averaged PGI2 generating capacity was closely correlated to the averaged PGI2 synthase activity in DOCA-salt hypertensive rats and three lines of control rats. Incontrast, phospholipase C and phospholipase A2, both of which liberate arachidonate for PGI2 synthesis, were rather lowered in DOCA-salt hypertensive rats. These data clearly indicate that vascular PGI2 generation is increased in the development of DOCA-salt hypertension and that PGI2 synthase is mainly responsible for this enhancement. The increased PGI2 synthase may be relevant to the blood pressure elevation and is expected to have beneficial effects on the vascular protection in hypertension.
 ...
PMID:Possible role of prostacyclin synthase in altered prostacyclin generation in DOCA-salt hypertensive rats. 193 Aug 48

Hypertension is associated with hyperinsulinemia in the presence or absence of obesity or glucose intolerance. Physiological concentrations of insulin decrease the catecholamine-induced production of prostaglandin I2 (PGI2; prostacyclin) and PGE2, two potent vasodilators, in adipose tissue, one of the largest organs in the body. This finding suggests that hyperinsulinemia increases peripheral vascular resistance and blood pressure by inhibiting the stimulatory effect of adrenergic agonists (and perhaps other agonists) on the production of PGI2 and PGE2 in adipose tissue (and perhaps other tissues). This concept is supported by evidence that PGI2 and PGE2 modulate vascular reactivity in states of health and disease. For example, during insulin deficiency, i.e., in diabetic ketoacidosis, PGI2 and PGE2 production by adipose tissue are increased, and peripheral vascular resistance and blood pressure are decreased. This hypothesis is also supported by evidence that blood flow through rat and human adipose tissue is decreased in obesity and that insulin decreases the blood flow through adipose tissue in nonobese rats. Thus, insulin may regulate PGI2 and PGE2 production by adipose tissue (and possibly other tissues) through a wide range of concentrations with important physiological and clinical consequences.
 ...
PMID:Insulin, prostaglandins, and the pathogenesis of hypertension. 193 84

The pioneering work of Furchgott, Moncada, and Vane has clearly established that the endothelium plays a critical role in the regulation of vascular tone. The endothelium produces several potent vasoactive substances, including vasodilators such as endothelium-derived relaxing factor and prostacyclin as well as vasoconstrictors such as angiotensin II and endothelin. These vasoactive substances not only have short-term effects on vascular tone but also appear to induce long-term effects on vascular structure. This process of vascular remodeling involves cell growth or regression and extracellular matrix expansion or contraction. As the interface between the bloodstream and the vessel wall, the endothelium plays a pivotal role in sensing and transducing the stimulus that induces vascular remodeling as well as producing the mediators that alter cell growth and the composition of the extracellular matrix. The endothelium maintains homeostasis within the vasculature by a balance between vasodilators and vasoconstrictors or growth inhibitors and growth promoters. Endothelial cell dysfunction may alter the delicate balance of mediators necessary to maintain homeostasis. Indeed, endothelial cell dysfunction is a common pathogenetic defect in animal models of hypertension as well as in hypertensive humans. Further understanding of the cellular and molecular mechanisms of vascular remodeling induced by endothelial cell-derived mediators may have important implications in the pathogenesis and treatment of hypertension.
Hypertension 1991 Nov
PMID:Endothelium and growth factors in vascular remodeling of hypertension. 193 73

Evidence continues to accumulate on the importance of paracrine substances formed in the vascular endothelium in the regulation of the vascular system. Those that relax the underlying smooth muscle include nitric oxide, prostacyclin, and an unidentified hyperpolarizing factor; those causing contraction include angiotensin II, endothelin, oxygen-derived free radicals, prostacyclin H2, and thromboxane A2. Determination of the mechanisms governing the formation and release of these substances in different blood vessels of the same species and in different species as well as the maintenance of the balance between them is important for understanding their role in normal circumstances and in diseases of the blood vessels. In this article, we will summarize the current understanding of the role of endothelium-derived relaxing factors and discuss the possibility that endothelial dysfunction may play a primary as well as a secondary role in the pathogenesis of primary hypertension. As a consequence of this dysfunction, substances formed in the endothelial cells at the sites of the arterial baroreceptors could lead to their resetting, resulting in less inhibition of the vasomotor centers, enhanced neurohumoral activity, and a consequential increase in systemic vascular resistance. This increase could be enhanced by a predominant action of endothelium-derived contracting factors in the resistance vessels. Proliferation of the vascular smooth muscle would follow, because of the mitogenic action of some of these factors and other growth promotors. By these mechanisms, the endothelium may participate in the polygenic dysfunction characteristic of primary hypertension, not only in initiating the increase in arterial blood pressure, but also in sustaining it.
Hypertension 1991 Nov
PMID:Endothelium-derived vasoactive factors: I. Endothelium-dependent relaxation. 193 90

Plasma 6-keto-prostaglandin F 1 alpha and thromboxane B2, the metabolites of prostacyclin and thromboxane A2 respectively, were measured in 12 women with pregnancy-induced hypertension, 12 age-matched normotensive pregnant women and 8 non-pregnant women as controls. Pregnancy was divided into 3 stages, namely: 22-27, 28-32 and 33-39 weeks. The concentrations of thromboxane B2 in the plasma of women with pregnancy-induced hypertension was 1.4-1.7 times greater than normotensive pregnant subjects at the same gestational stage, and 2 times higher than controls. Plasma levels of 6-keto-prostaglandin F 1 alpha in normotensive pregnant women was 1.8 times greater than in those with pregnancy-induced hypertension at 28-32 and 33-39 weeks, and was significantly higher than control. The ratio of thromboxane B2 to 6-keto-prostaglandin F 1 alpha was markedly increased in the group of patients with pregnancy-induced hypertension at 28-32 and 33-39 weeks gestation. The ratio of the two metabolites in normotensive patients at each stage of gestation was similar to the control group. The ratio of circulating aggregated platelets in subjects with pregnancy-induced hypertension was significantly lower than in normotensive pregnant subjects at 33-39 weeks, implying increased turnover of platelets in pregnancy-induced hypertension. There was no significant difference in count of platelets, adenosine diphosphate threshold concentration and variables of platelet aggregation induced by adenosine diphosphate among the 3 groups.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The role of aggregation of platelets in pregnancy-induced hypertension: a comprehensive and longitudinal study. 193 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>