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

Two independent series of biomedical investigations have led to the discovery that the atria constitute a peptide-secreting endocrine gland. The first investigation is mainly morphological and started with the finding that mammalian atrial (but not ventricular) cardiocytes contain "dense bodies." These "dense bodies," later called "specific granules," were found to be different from lysosomes; to be made up of proteins; and to incorporate both 3H-leucine and 3H-fucose in a pattern typical of peptide-secreting endocrine cells. The finding that rat atrial granulation varied with the sodium and water balance led to the crucial observation that atrial extracts have natriuretic and diuretic effects. In less than five years, this new natriuretic hormone has been purified, sequenced and synthesized, and its CDNA and gene have been cloned. The atrial natriuretic factor (ANF) gene has been assigned to the distal short arm of chromosome 1 in band 1P36, while the mouse gene is localized in chromosome 4. The native and synthetic hormones exert identical wide ranging effects (possibly through particulate guanylate cyclase stimulation and adenylate cyclase inhibition) on the kidney, blood vessels, adrenal cortex, and pituitary. Physiopathologic implications of the hormone in experimental hypertension, congestive heart failure, and expansion of blood volume are already beginning to emerge. Concurrently, the search for the function of natriuretic hormones or factors (through studies of negative pressure breathing, atrial distension experiments, head-out water immersion, expansion of blood volume, Na+/K+-ATPase inhibition, and parabiosis experiments in Dahl rats) has provided a general framework within which to interpret this new cardiac function.
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PMID:The heart as an endocrine gland. 302 9

There is evidence that atrial natriuretic factor (ANF) has an action in the inner medullary collecting duct. In addition, the prehypertensive Dahl salt-sensitive (S) rat has an intrinsic tendency toward less natriuresis than the Dahl salt-resistant (R) rat has when challenged with ANF. To test the hypothesis that renal papillary collecting tubule cells from prehypertensive S rats might be genetically less responsive to ANF, S and R cells were grown in culture and studied for responsiveness to ANF by measurement of cyclic nucleotide responses. There was a concentration-dependent effect of ANF on renal papillary collecting tubule cell synthesis of intracellular cyclic guanosine 3',5'-monophosphate (cGMP) in both strains. However, the S cells were hyporesponsive compared with the R cells (p less than 0.002, by analysis of variance). Likewise, in response to Na nitroprusside, the S cells were hyporesponsive compared with the R cells as measured by intracellular cGMP accumulation (p less than 0.03, by analysis of variance). Arginine vasopressin stimulated intracellular cAMP equally in both strains. Also, ANF equally enhanced intracellular cGMP in glomerular mesangial cells from S and R rats, indicating possible specificity of the reduced responsiveness to ANF to the distal nephron of S rats. Plasma ANF levels had a slight tendency to be higher in prehypertensive S rats than in R rats (p = 0.088, by t test). These results suggest that the papillary collecting duct of Dahl S and R rats may differ in guanylate cyclase activity. This difference may partially explain the impaired natriuretic responses of S rats and could represent a factor contributing to the development of salt-sensitive hypertension.
Hypertension 1987 Jul
PMID:Papillary collecting tubule responsiveness to atrial natriuretic factor in Dahl rats. 303

Endothelium-derived relaxing factor (EDRF) is a labile humoral agent released by vascular endothelium that mediates the relaxation induced by some vasodilators, including acetylcholine and bradykinin. EDRF also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to vascular endothelium. These actions of EDRF are mediated through stimulation of the soluble guanylate cyclase and the consequent elevation of cyclic guanosine 3',5'-monophosphate. EDRF has been identified as nitric oxide (NO). The pharmacology of NO and EDRF is indistinguishable; furthermore, sufficient NO is released from endothelial cells to account for the biological activities of EDRF. Organic nitrates exert their vasodilator activity following conversion to NO in vascular smooth muscle cells. Thus, NO may be considered the endogenous nitrovasodilator. NO is synthesized by vascular endothelium from the terminal guanido nitrogen atom(s) of the amino acid L-arginine. This indicates the existence of an enzymic pathway in which L-arginine is the endogenous precursor for the synthesis of NO. The discovery of the release of NO by vascular endothelial cells, the biosynthetic pathway leading to its generation, and its interaction with other vasoactive substances opens up new avenues for research into the physiology and pathophysiology of the vessel wall.
Hypertension 1988 Oct
PMID:The discovery of nitric oxide as the endogenous nitrovasodilator. 304 40

Endothelial cells release a potent vasodilator which activates guanylate cyclase and thereby induces relaxation of vascular smooth muscle cells. The so-called endothelium-derived relaxing factor (EDRF) is released by acetylcholine, local and circulating hormones, and substances released from aggregating platelets or formed during activation of the coagulation cascade. Nitric oxide (NO) probably accounts for the factor's activity. Thus, endothelial cells produce endogenous nitrates causing vasodilatation and inhibition of platelet adhesion and aggregation. Under physiological conditions, EDRF may play a role in the prevention of vasospasm and thrombosis. On the other hand, the impairment of endothelial regulatory mechanisms in atherosclerosis and hypertension may be involved in the pathogenesis of vascular occlusion and thereby of myocardial infarction, stroke and peripheral vascular disease.
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PMID:[Endothelium-derived relaxing factor(s): endogenous nitrates in the circulation?]. 306 71

In the aortas and mesenteric arteries from spontaneous hypertensive rats and in the aortas from stress- and desoxycorticosterone-acetate-hypertensive rats, the intracellular cGMP: cAMP ratios were significantly elevated when compared to the ratios in the aortas of the respective controls. Decreases in the intracellular cAMP or cGMP levels were consistently associated with increased activity of the cyclic-nucleotide-specific low K(m) phosphodiesterase (3':5'-cAMP 5' nucleotidohydrolase, EC 3.1.4.17). Increases in intracellular cGMP levels were associated with elevated guanylyl cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity. Furthermore, adenylyl cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity was less sensitive to stimulation by the beta-adrenergic stimulant isoproterenol in both the aortas and the hearts of the hypertensive animals. These changes could provide the biochemical basis for the (a) increased vascular smooth muscle tone and peripheral resistance observed in these animals, (b) increased reactivity to norepinephrine, and (c) decreased ability of aortas from hypertensive rats to relax. The presence of these same effects in different etiologic types of hypertension indicates that this aberration in cyclic nucleotide metabolism may represent a common metabolic defect basic to the hypertensive syndrome irrespective of etiology.
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PMID:Aberrations of cyclic nucleotide metabolism in the hearts and vessels of hypertensive rats. 415 74

Hypertension and atherosclerosis are associated with structural and functional changes that may be collectively described as a 'sick vessel syndrome'. Structural changes in blood vessels (remodelling and hypertrophy) may be protective and adaptive. Functional changes in blood vessels include impairment of endothelium-dependent relaxation and impaired relaxation in response to activation of ATP-sensitive potassium channels. In general, vasorelaxation in response to direct activation of adenylate and guanylate cyclase is preserved in chronic hypertension and atherosclerosis. Vasoconstrictor responses to selected stimuli, such as serotonin, may be greatly potentiated. Impairment of endothelial function in combination with exaggeration of vasoconstrictor responses may predispose to vasospasm particularly during atherosclerosis.
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PMID:Sick vessel syndrome: vascular changes in hypertension and atherosclerosis. 747 26

Endothelium-derived relaxing factor and exogenous nitrovasodilators are thought to produce smooth muscle relaxation by activation of soluble guanylate cyclase. To investigate whether diminished cyclic GMP (cGMP) accumulation underlies the differences in vascular reactivity to nitrovasodilators between Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR), we determined cGMP formation in aortic smooth muscle cells from the two strains. Both cultured cells and aortic rings from 12- to 14-week-old SHR accumulated greater amounts of cGMP on stimulation with exogenous nitrovasodilators (ie, sodium nitroprusside) than those from WKY rats, whereas there was no difference observed in cells from prehypertensive animals (5- to 6-week old) between the two strains. Responsiveness of smooth muscle cells to endothelium-derived relaxing factor was investigated in cocultures of bovine aortic endothelial cells (BAE) and smooth muscle cells from SHR and WKY rats. cGMP accumulation elicited by endothelium-derived relaxing factor released either basally or in response to bradykinin and the calcium ionophore A23187 was greater in smooth muscle from 12- to 14-week-old SHR than from age-matched WKY rats (80 +/- 17 versus 11 +/- 2 for basal; 152 +/- 12 versus 80 +/- 26 for A23187; 163 +/- 21 versus 40 +/- 12 pmol/mg protein per 15 minutes for bradykinin) in SHR/BAE and WKY/BAE cocultures, respectively. Northern blot analysis of steady-state messenger RNA levels for the beta 1 subunit of soluble guanylate cyclase revealed higher levels of the message in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Apr
PMID:Smooth muscle cell responsiveness to nitrovasodilators in hypertensive and normotensive rats. 751 69

8-Bromo-guanosine 3':5'-cyclic monophosphate (8-Br-cGMP), an analogue of cyclic guanosine monophosphate (cGMP), induced a time- and dose-dependent enhancement of interleukin-1-induced nitric oxide production in vascular smooth muscle cells. Human atrial natriuretic polypeptide, which stimulates cGMP accumulation in vascular smooth muscle cells, also enhanced interleukin-1-induced nitric oxide release at a concentration of 100 nmol/L. In contrast, coincubation with 10 mumol/L methylene blue, an inhibitor of soluble guanylate cyclase, inhibited interleukin-1-induced nitric oxide release from vascular smooth muscle cells. Furthermore, coincubation with 8-Br-cGMP also enhanced the interleukin-1-induced increase in inducible nitric oxide synthase messenger RNA in vascular smooth muscle cells. However, the enhancement of nitric oxide production induced by 8-Br-cGMP was significantly prevented by coincubation with neutralizing antibody against tumor necrosis factor-alpha. Furthermore, 8-Br-cGMP enhanced the interleukin-1-induced increase in tumor necrosis factor-alpha messenger RNA level in vascular smooth muscle cells. These findings indicate that cGMP may upregulate inducible nitric oxide synthase gene expression through the stimulation of tumor necrosis factor-alpha production in vascular smooth muscle cells. Thus, there may be a positive feedback mechanism between nitric oxide and the cGMP system in vascular smooth muscle cells.
Hypertension 1995 Apr
PMID:cGMP upregulates nitric oxide synthase expression in vascular smooth muscle cells. 753 12

Nitric oxide may act at autonomic sites in the brain to regulate arterial blood pressure. Our goal was to determine whether gene expressions of the brain isoform of nitric oxide synthase and of the beta subunit of soluble guanylyl cyclase, the target of nitric oxide, were altered in discrete autonomic brain regions after induction of hypertension in rats. The two-kidney, one clip model was used to induce hypertension, and measurements were made 3 and 6 weeks after the left renal artery was clipped. Only experimental rats with blood pressures elevated by at least 25 mm Hg were used. Total RNA was purified from microdissected tissue blocks containing hypothalamus, dorsal medulla, rostral ventrolateral medulla, and caudal ventrolateral medulla. Changes in nitric oxide synthase and guanylyl cyclase mRNA were semiquantified in each region by use of reverse transcription-polymerase chain reactions in which known concentrations of deletion mutants of the two genes were coamplified as internal standards. Compared with controls, significant decreases and increases in nitric oxide synthase mRNA were found in the hypothalamus (x 2.2) and caudal ventrolateral medulla (x 6.4), respectively, of hypertensive rats 3 weeks after clipping. These alterations were reversed in hypertensive rats at 6 weeks; levels increased (x 4.6) in the hypothalamus and decreased (x 5.5) in the caudal ventrolateral medulla. Changes in guanylyl cyclase expression paralleled those for nitric oxide synthase in some but not all areas at both time points.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Jul
PMID:Gene expression of brain nitric oxide synthase and soluble guanylyl cyclase in hypothalamus and medulla of two-kidney, one clip hypertensive rats. 754 80

1. Impaired endothelium-dependent relaxation has been previously demonstrated in blood vessels of hypertensive rats and in humans with essential hypertension. Arteries from spontaneously hypertensive rats have been shown to produce, in response to high concentrations of acetylcholine, a vasoconstrictor substance called endothelium-derived contracting factor, the production of which can be inhibited by indomethacin or other cyclo-oxygenase inhibitors, suggesting that it is a prostanoid. The mechanisms involved in endothelium-dependent relaxation of human arteries are unclear, and the potential generation of endothelium-derived contracting factor by endothelium in human hypertension has not been established. 2. We investigated the effects of acetylcholine on precontracted small arteries dissected from gluteal subcutaneous fat biopsies from normotensive subjects and subjects with borderline and mild essential hypertension. Vessels from normotensive subjects and those from borderline hypertensive patients, precontracted by noradrenaline, were relaxed completely by acetylcholine, whereas those from patients with mild essential hypertension relaxed slightly but significantly less, indicating that generation of endothelium-derived relaxing factor (endothelium-derived nitric oxide) was only minimally reduced or that production of minor amounts of endothelium-derived contracting factor occurred in small arteries from these hypertensive subjects. This impairment of endothelium-dependent relaxation was not corrected by indomethacin, which indicated that the contribution of endothelium-derived contracting factor, if any, was minimal in this subset of essential hypertensive patients. In contrast, mesenteric small arteries of adult spontaneously hypertensive rats presented strong contractions in response to the higher concentrations of acetylcholine, which were abolished by exposure to indomethacin. 3. The relaxation induced by acetylcholine in arteries from both hypertensive and normotensive humans was partially blunted (by 30%) by pretreatment with 0.1 mmol/l NG-nitro-L-arginine methyl ester or NG-nitro-monomethyl-L-arginine (inhibitors of nitric oxide synthase) and by 10 mumol/l Methylene Blue (a blocker of soluble guanylate cyclase), indicating the role of endothelium-derived nitric oxide and the generation of its intracellular second messenger cyclic guanosine monophosphate in acetylcholine-induced relaxation. The remaining relaxation elicited by acetylcholine could be blocked with 30 mmol/l KCl or with 10 mumol/l ouabain (inhibitor of Na+, K(+)-ATPase), and, when combined with NG-nitro-L-arginine methyl ester, these interventions abolished acetylcholine-induced relaxation. Tolbutamide at 2 mmol/l or 10 mumol/l glyburide (blockers of ATP-sensitive potassium channels) partially inhibited NG-nitro-L-arginine methyl ester-resistant endothelium-dependent relaxation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endothelium-dependent relaxation of small arteries from essential hypertensive patients: mechanisms and comparison with normotensive subjects and with responses of vessels from spontaneously hypertensive rats. 754 95


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