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

EDRF is a potent, endogenous vasodilator that is produced and released from endothelial cells and subsequently causes the relaxation of VSM through the activation of soluble guanylate cyclase and an increase in VSM cyclic GMP. Structurally, EDRF is likely to be NO or a related nitrogen oxide-containing compound. It is synthesized in endothelial and other cell types from L-arginine by a calcium-calmodulin and NADPH-dependent enzyme. Its action is very similar to the nitrovasodilators that act directly on VSM. EDRF is present in all vascular beds, large and small vessels, and in a wide range of species. Its role in human vascular physiology and pathophysiology is just beginning to be understood. EDRF is a potent endogenous vasodilator and inhibitor of platelet aggregation and adhesion. Its activity is impaired in hypertension and atherosclerosis, and its absence due to endothelial damage may play a role in cerebral and coronary vasospasm. It is a mediator of flow-dependent vasodilation, and its inhibition by hypoxia may contribute to the hypoxic pulmonary vasoconstrictor response. Endothelial cell damage and impairment of EDRF production may also contribute to acute and chronic pulmonary hypertension. A further understanding of the chemical nature and synthetic pathways of EDRF should lead to the production of analogs and antagonists, which may play an important role in future treatments for atherosclerosis, myocardial infarction, angina, hypertension, and other vascular diseases. The recent realization that EDRF serves as the second messenger for guanylate cyclase activation and cyclic GMP production in a variety of cell types outside of the cardiovascular system, including renal and respiratory epithelium, cerebellar neurons, macrophages, and adrenocytes, suggests even broader implications. The importance of EDRF to the anesthesiologist may go beyond an understanding of its role in cardiovascular physiological and pathophysiological states. Initial studies have shown that the endothelium may play a role in mediating the vascular actions of anesthetics, and that anesthetics can inhibit the production, release, or action of EDRF. How are these interactions mediated? Are there significant differences between anesthetics with regard to their effects on EDRF? Is there a clinically significant effect of anesthetics on basal activity of EDRF, or only in response to exogenous stimulation? Conversely, it is important to determine if alterations in endothelial cell function by various disease states such as hypertension, atherosclerosis, adult respiratory distress syndrome, cerebral vasospasm, and others cause changes in the vascular actions of anesthetics. The potential interactions of anesthetics with EDRF production and action in cell types other than the endothelium have not yet been explored.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endothelium-derived relaxing factor: basic review and clinical implications. 186 89

The endothelium-derived relaxing factor (EDRF) is nitric oxide (NO) or a closely related nitrosothiol derivative, and is formed from the amino acid, L-arginine. NO is rapidly inactivated locally, released into the blood stream and instantly destroyed by haemoglobin. EDRF-NO and NO generated from vasodilator nitrates work by activation of soluble guanylate cyclase, elevating cyclic guanosine monophosphate (GMP) levels to cause vasodilatation and inhibition of platelet aggregation. Endothelium-dependent vasodilatation is attenuated in hypertension, atherosclerosis and diabetes through either loss of endothelium or deficient formation of EDRF-NO. In these conditions exogenous nitrates may substitute for a failing endogenous mechanism.
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PMID:Endogenous nitrates--implications for treatment and prevention. 187 72

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.
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PMID:Endothelium-derived relaxing and contracting factors. 187 96

The nitrovasodilators, nitroglycerin and sodium nitroprusside, cause both arterial and venous smooth muscle dilation by the intracellular release of nitric oxide. Nitric oxide activates guanylate cyclase, resulting in an accumulation of cyclic GMP. The endogenous formation of nitric oxide results in vasodilatory activity similar to the nitrovasodilators. Nitroglycerin is commonly used in the treatment of angina pectoris because of its ability to decrease myocardial oxygen consumption. Most likely, this response occurs as a result of a reduction in preload, which can decrease arterial wall tension and improve coronary blood flow. This pharmacologic effect warrants the use of nitroglycerin in the treatment of myocardial ischemia or infarction, congestive heart failure, and hypertension. Sodium nitroprusside is effective in reducing arterial blood pressure in hypertensive crisis as a result of systemic vasodilation leading to a reduction in preload and afterload. Sodium nitroprusside is not as effective in the treatment of angina pectoris or in diminishing of myocardial ischemia because it does not preferentially improve blood flow to ischemic myocardium over nonischemic myocardium. Inhibition of platelet aggregation has been demonstrated with these drugs, but the clinical applications need further investigation. Nursing interventions for the patient on nitrovasodilator therapy include careful hemodynamic monitoring and drug infusion, along with elimination of physical and emotional stimuli that can aggravate the patient's underlying pathology.
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PMID:Pharmacology of the nitrovasodilators. Antianginal, antihypertensive, and antiplatelet actions. 190 76

Nitric oxide first captured the interest of biologists when this inorganic molecule was found to activate cytosolic guanylate cyclase and stimulate cyclic guanosine monophosphate (GMP) formation in mammalian cells. Further studies led to the finding that nitric oxide causes vascular smooth muscle relaxation and inhibition of platelet aggregation by mechanisms involving cyclic GMP and that several clinically used nitrovasodilators owe their biological actions to nitric oxide. Nitric oxide possesses physicochemical and pharmacological properties that make it an ideal candidate for a short-term regulator or modulator of vascular smooth muscle tone and platelet function. Nitric oxide is synthesized by various mammalian tissues including vascular endothelium, macrophages, neutrophils, hepatic Kupffer cells, adrenal tissue, cerebellum, and other tissues. Nitric oxide is synthesized from endogenous L-arginine by a nitric oxide synthase system that possesses different cofactor requirements in different cell types. The nitric oxide formed diffuses out of its cells of origin and into nearby target cells, where it binds to the heme group of cytosolic guanylate cyclase and thereby causes enzyme activation. This interaction represents a novel and widespread signal transduction mechanism that links extracellular stimuli to the biosynthesis of cyclic GMP in nearby target cells. The small molecular size and lipophilic nature of nitric oxide enable communication with nearby cells containing cytosolic guanylate cyclase. The extent of transcellular communication is limited by the short half-life of nitric oxide, thereby ensuring a localized response. Labile nitric oxide-generating molecules such as S-nitrosothiols may be involved as precursors or effectors. Further research will provide a deeper understanding of the biology of nitric oxide and the nature of associated pathophysiological states.
Hypertension 1990 Nov
PMID:Nitric oxide. A novel signal transduction mechanism for transcellular communication. 197 98

To investigate the possible relationship of hypertension and the N-terminus of the atrial natriuretic factor (ANF) prohormone which contains two peptides [i.e. pro ANF-(1-30) and pro-ANF-(31-67)] with blood pressure-lowering effects, we examined the circulating levels of the N-terminus of the ANF prohormone in three patients with pheochromocytomas before surgery, during an increase in their blood pressure with surgical manipulation of their tumors, and after surgery when their blood pressures returned to normal. The circulating levels of the whole N-terminus [amino acids 1-98; pro-ANF-(1-98)] and pro-ANF-(31-67) from the midportion of the N-terminus of the ANF prohormone were increased 2-fold in patients with both extraadrenal and intraadrenal pheochromocytomas. In both the intraadrenal and extraadrenal patients N-terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) circulating levels increased further during surgical manipulation and returned to normal after surgical removal of their respective tumors. Each of these pheochromocytomas was found to have pro-ANF-(1-30) and -(31-67)-binding sites that were functional, since they could enhance the guanylate cyclase-cGMP system 2-fold in these pheochromocytomas. The entire 126 amino acids of the prohormone were present within each of the pheochromocytomas, since both the whole N-terminus and C-terminus (i.e. ANF) of the prohormone were present. Examination of the pheochromocytomas by electron microscopy revealed electron-dense granules similar to those in the heart, which have been associated with the synthesis and storage of the ANF prohormone. We conclude that 1) the whole N-terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) of the ANF prohormone circulate at higher concentrations in persons with pheochromocytomas and return to normal with removal of the tumors; 2) pheochromocytomas contain specific binding sites for pro-ANF-(1-30) and -(31-67); 3) these binding sites are functional, since pro-ANF-(1-30) and -(31-67) could enhance the enzyme guanylate cyclase within these tumors; and 4) the entire 126 amino acids of the ANF prohormone are present within these tumors, which have electron-dense granules associated with polypeptide hormone synthesis, suggesting that the ANF prohormone is being synthesized within the pheochromocytomas.
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PMID:Increased circulating concentration of the N-terminus of the atrial natriuretic factor prohormone in persons with pheochromocytomas. 197 56

Endothelium-dependent relaxation of carotid arteries and changes in levels of cyclic (c)GMP between stroke-prone spontaneously hypertensive (SHRSP) and Wistar-Kyoto (WKY) rats have been compared. The concentration-response curve for acetylcholine (ACh)-induced relaxation was shifted to the right in carotid arteries from SHRSP. Relaxation responses produced by calcimycin (A 23187) and melittin, both endothelium-dependent agents, were depressed in carotid arteries from SHRSP. Relaxation responses produced by sodium nitroprusside and 8-Br-cGMP were similar to those in strips from WKY. ACh-induced production of cGMP was significantly decreased in carotid arteries from SHRSP when compared with the level for similarly treated strips from WKY. These results suggest that functional changes in endothelium, but not guanylate cyclase activity or cGMP sensitivity in the carotid arteries, may occur in hypertension. Thus, impaired endothelium-dependent relaxation in SHRSP may play an important role in hypertensive vascular diseases such as stroke.
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PMID:Impairment of endothelium-dependent relaxation and changes in levels of cyclic GMP in carotid arteries from stroke-prone spontaneously hypertensive rats. 198 99

This paper review the actual knowledges about the physiological role of nitric oxide, sintetized from amino acid L-arginine. The nitric oxide sintetized in the vascular endothelium has a fundamental role in vascular tone, blood flow and arterial pressure control, acting stimulating guanylate cyclase on vascular smooth muscle. Nitric oxide could be considered the endogenous nitrovasodilator. Its action on the cardiovascular system are imitated by nitroglycerine, sodium nitroprusside and related compounds. Probably the disturbance in the synthesis or release of nitric oxide may be involved in the pathophysiology of hypertension, vasospasm and atherosclerosis. Recently has been shown that nitric oxide synthesis from L-arginine also occurs in other different cells like macrophages, central nervous system, liver, neutrophils, adrenal glands, playing different biological effects. Changes in nitric oxide synthesis or action in those systems, could be related to different pathological disorders as inflammation, atherosclerosis and cancer. The found of a substance as simple as nitric oxide, let suppose that we are in the presence of a biological mediator with a very early evolutionary origin, probably widespread in all the animal kingdom, and which represents the universal transduction system for activation of the soluble guanylate cyclase enzyme.
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PMID:[Nitric oxide: from endogenous vasodilator to biologic mediator]. 209 54

We reported that dexamethasone treatment of rabbits causes a reduction in renal vasoconstrictor responses to prostaglandin F2 alpha and U46619, an agonist at the thromboxane-endoperoxide receptor, but not to phenylephrine. The purpose of this study was to examine if dexamethasone treatment can affect the renal vasodilatory responses to prostacyclin (PGI2) and prostaglandin E2 (PGE2) in isolated Krebs-perfused kidneys constricted with phenylephrine. In kidneys from dexamethasone-treated rabbits, the vasodilatory response to PGI2 was reduced by 57%, whereas that to PGE2 was converted to a vasoconstrictor response. This effect of dexamethasone appears to be specific in that the renal vasodilatory responses to forskolin and to sodium nitroprusside were not affected by the steroid. Contrasting with the inhibitory effect of dexamethasone on prostanoid-induced renal vasodilation, treatment with dexamethasone augmented the renal vasodilatory response to arachidonic acid; for example, arachidonic acid, at 10 micrograms decreased perfusion pressure by 24.8 +/- 5.4 and 49.0 +/- 5.6 mm Hg in kidneys from vehicle- and dexamethasone-treated rabbits, respectively. The enhanced vasodilatory effect of arachidonic acid could not be attributed to increased renal formation of PGE2 and PGI2. In conclusion, dexamethasone interferes with prostanoid-mediated renal vasodilation, which is not associated with an impairment in renal responsiveness to direct activators of adenylate cyclase and guanylate cyclase. The reciprocal effect of dexamethasone on the renal vascular responses to arachidonic acid and vasodilatory prostanoids are indicative of a previously unrecognized influence of glucocorticoids on the renal arachidonate-prostaglandin system.
Hypertension 1990 Feb
PMID:Reciprocal effects of dexamethasone on vasodilatory responses to arachidonic acid and prostanoids in the isolated perfused rabbit kidney. 210 68

Acute coadministrations of an inhibitor of endopeptidase 24.11 (thiorphan) and a ligand (SC-46542) selective for the non-guanylate cyclase-linked atriopeptin binding sites increases urinary sodium excretion to a greater degree in conscious spontaneously hypertensive rats than in normotensive Wistar-Kyoto rats. In the present study, we examined the effects of chronic 10-day intravenous infusions of SC-46542 (des[Phe106,Gly107,Ala115,Gln116] atriopeptin-(103-126] (0.1 mg/kg/hr), thiorphan (1.5 mg/kg/hr), and atriopeptin-(103-126) (100 ng/hr) alone or in combination on direct recording of mean arterial pressure in conscious spontaneously hypertensive rats. During an 11-day time-control infusion of isotonic saline vehicle (100 microliters/hr), mean arterial pressure remained stable. Chronic infusion of atriopeptin-(103-126) decreased mean arterial pressure progressively over the first 3 days; then mean arterial pressure progressively rose to control level over the following 3 days and remained at control level for the remainder of the experiment. Similarly, coinfusions of atriopeptin-(103-126) and SC-46542 or thiorphan, SC-46542 and thiorphan, or the triple infusion of atriopeptin-(103-126), SC-46542, and thiorphan had only transient effects on mean arterial pressure during 10-day infusions. SC-46542 alone had no effect on mean arterial pressure. Similarly, thiorphan alone had no effect on mean arterial pressure except at doses that blocked the acute pressor response to angiotensin I. Chronic infusions of atriopeptin-(103-126), SC-46542, and thiorphan alone or in combination are not effective long-term treatments for hypertension in spontaneously hypertensive rats.
Hypertension 1990 Dec
PMID:Chronic atriopeptin regulation of arterial pressure in conscious hypertensive rats. 214 72


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