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)

Reactive oxygen species, such as superoxide and nitric oxide (NO), have been postulated to underlie the pathogenesis of various diseases. About 3 to approximately 10% of the oxygen utilized by tissues is converted to its reactive intermediates that impair cells and tissues. However, only a limited information supporting this hypothesis is available predominantly because of the short half life of these intermediates. To elucidate the role of superoxides and related metabolites in the pathogenesis of various diseases, two superoxide dismutase derivatives were synthesized; one (SM-SOD) circulates bound to albumin and accumulates in tissues with decreased pH and the other (HB-SOD) binds to vascular endothelial cells by a heparin-inhibitable mechanism. NO was first recognized as a potent vasorelaxant. NO rapidly diffuses across cells and binds to various proteins, such as guanylate cyclase, thereby modulating cellular metabolism. Because NO also reacts with superoxide and molecular oxygen, the two molecules might be major determinants of its half life and strongly affect its biological functions. In fact, targeting HB-SOD to vascular endothelial cells increased the cGMP levels in arterial walls and normalized the blood pressure of animals with genetic and nongenetic hypertension. Thus, the imbalance between superoxide and NO seems to underlie the pathogenesis of hypertension. NO forms a dissociable complex with cytochrome c oxidase in mitochondria and regulates cellular energy metabolism particularly under physiologically low oxygen tensions. Thus, cross-talk between oxygen, NO and superoxide radicals might play a critical role in regulating circulation and energy metabolism. Oxidative stress causes an imbalance in this cross-talk and underlies the pathogenesis of various diseases.
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PMID:[Role of oxidative stress in health and disease]. 893 79

1. To elucidate the physiological and pathophysiological role of the natriuretic peptide system in the progression of hypertensive renal disease, we examined the gene expression of natriuretic peptide receptor subtypes, guanylate cyclase-A (GC-A), guanylate cyclase-B (GC-B) and clearance receptor (C receptor), in the kidney of stroke-prone spontaneously hypertensive rats (SHRSP) at 8 and 20 weeks of age, and compared them with their gene expression in age-matched Wistar-Kyoto (WKY) rats. 2. Northern blot analyses revealed that messages for three natriuretic peptide receptor subtypes were expressed in the kidney, and their expressions were higher in the glomeruli than in the whole kidney in each strain. 3. In 20 week old rats with established hypertension, the glomerular concentration of GC-A mRNA was significantly higher in SHRSP than in WKY. The concentrations of GC-B and C receptor mRNA in the glomeruli tended to increase and decrease, respectively, but they were not statistically significant in SHRSP. 4. In 8 week old rats, the glomerular concentrations of GC-A, GC-B and C receptor mRNA were not significantly different between SHRSP and WKY. 5. This study demonstrates that in the progression of hypertension, the expression of GC-A, which mediates biological actions of natriuretic peptides, is enhanced in the kidney of SHRSP compared to that of WKY. Together with the augmented secretion of the ligands previously revealed, altered expression of natriuretic peptide receptor subtypes in SHRSP may have a deterrent role in the development of hypertension and its renal complications.
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PMID:Altered gene expression of natriuretic peptide receptor subtypes in the kidney of stroke-prone spontaneously hypertensive rats. 907 45

Three atrial natriuretic peptide (ANP) receptors, ANP(A), ANP(B), and ANP(C), have been identified in the heart, suggesting that natriuretic peptides may have direct effects on cardiac function. To characterize the possible role of atrial natriuretic peptide (ANP) in the regulation of its own secretion, we studied here the effects of ANP (greater affinity for ANP(A) than for ANP(B) receptors) and C-type natriuretic peptide (CNP), a potent activator of ANP(B) receptors, on the release of atrial peptides under basal conditions and during acute volume expansion in conscious normotensive Sprague-Dawley rats. The effects of HS-142-1, a nonpeptide ANP(A) and ANP(B) receptor antagonist, on volume load-induced atrial peptide release in 1-yr-old conscious normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were also studied. As an index of secretion of atrial peptides from the heart, plasma levels of N-terminal fragment of pro-ANP (NT-ANP) were measured. In Sprague-Dawley rats, i.v. infusion of ANP for 30 min in doses of 0.3 and 1.0 microg/kg x min blocked the plasma immunoreactive NT-ANP (IR-NT-ANP) response to volume load (P < 0.001), whereas CNP had no significant effect. Neither ANP nor CNP infusion had any effect on plasma IR-NT-ANP levels under basal conditions. Bolus administration of HS-142-1 increased baseline plasma IR-ANP concentrations in both WKY and SHR strains (WKY: 3 mg/kg, 46 +/- 8 pmol/liter, P < 0.001; SHR: 1 mg/kg, 26 +/- 9 pmol/liter, P < 0.01; SHR: 3 mg/kg, 40 +/- 12 pmol/liter, P < 0.01). The corresponding increases in plasma IR-NT-ANP concentrations in the SHR in response to administration of HS-142-1 were 0.17 +/- 0.06 nmol/liter (P < 0.01) and 0.40 +/- 0.14 nmol/liter (P < 0.01). Moreover, HS-142-1 (3 mg/kg) augmented plasma IR-ANP and IR-NT-ANP responses to acute volume load in WKY rats. In contrast, HS-142-1 did not enhance the plasma IR-ANP response to acute volume load in SHR and resulted in a smaller increase in the plasma IR-NT-ANP concentration in SHR than in WKY rats. In conclusion, the findings that ANP, but not CNP, inhibited volume expansion-stimulated NT-ANP release and that HS-142-1, an antagonist of guanylate cyclase-linked natriuretic peptide receptors, increased plasma ANP and NT-ANP concentrations show that endogenous ANP directly modulates its own release via ANP(A) receptors in vivo. Furthermore, this modulation of acute volume expansion-induced atrial peptide release appears to be altered in experimental hypertension.
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PMID:Atrial natriuretic peptide (ANP) inhibits its own secretion via ANP(A) receptors: altered effect in experimental hypertension. 911 84

We compared the abundance and sensitivity of atrial natriuretic peptides (ANP) receptors in the brains of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats and examined the effect of blood pressure on the abundance of brain ANP receptors in several other experimental rat models. Brain slices from SHR generated more guanosine 3',5'-cyclic monophosphate in response to ANP than brain slices from WKY rats. No differences were found in brain particulate guanylate cyclase activity in both strains of rats. In rat brain homogenates, we observed that ANP bound in a specific and saturable fashion to samples from WKY rats, but not in samples from SHR. In vitro receptor autoradiography revealed that ANP binding was reduced in the subfornical organ, the choroid plexus, and the paraventricular nucleus of SHR compared with WKY rat brains. Correction of hypertension in SHR or induction of hypertension in other strains did not affect ANP binding in any of these brain regions. Altogether, our data suggest that the increased sensitivity of SHR brains to the action of ANP may be a consequence of factors other than the abundance of receptors and that it is not secondary to the elevation of blood pressure.
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PMID:Comparison of ANP binding and sensitivity in brains from hypertensive and normotensive rats. 914 39

In rat atria isolated with their cardioaccelerans nerves and labeled with [3H]norepinephrine, exposure to 1 x 10(-7) mol/L angiotensin II (Ang II) and 1 x 10(-7) mol/L Ang-(1-7) increased the release of radioactivity elicited by nerve stimulation (0.5-millisecond-long square-wave pulses at 2 Hz during 2 minutes) by 90% and 60%, respectively. The facilitatory effect on noradrenergic neurotransmission caused by both peptides was stereospecifically prevented by N omega-nitro-L-arginine methyl ester (1 x 10(-4) mol/L), an inhibitor of nitric oxide synthase that catalyzes the conversion of L-arginine to nitric oxide, as well as by 1 x 10(-5) mol/L methylene blue, a substance that inhibits the guanylate cyclase considered as the final target of nitric oxide action. On the other hand, the precursor of nitric oxide synthesis. L-arginine (1 x 10(-3) mol/L), reversed the prevention produced by N omega-nitro-L-arginine methyl ester on the increased release of norepinephrine caused by Ang II and Ang-(1-7). The present results suggest that nitric oxide could be involved in the neuromodulatory function elicited by both Ang II and Ang-(1-7) in rat atria. The physiological role of this observation is still under study.
Hypertension 1997 Jun
PMID:Possible participation of nitric oxide in the increase of norepinephrine release caused by angiotensin peptides in rat atria. 918 Jun 39

We have recently reported in normal isolated-perfused rat lungs that low basal tone appears to be regulated by nitric oxide (NO)-dependent and -independent mechanisms of soluble guanylate cyclase activation. In this study, we examined the role of NO in the regulation of pulmonary artery (PA) tone from rats with renin-dependent hypertension. Rats were made hypertensive by ligating the abdominal aorta above the left and below the right renal artery (aortic coarctation, AC). Mean arterial pressure significantly increased from 119 +/- 8.4 mmHg in control animals to 156 +/- 15 mmHg 7-14 days after AC surgery. PA pressures, however, remained unchanged (8.5 +/- 3.4 mmHg in control animals vs. 11 +/- 3.3 mmHg in AC animals). Hypoxic contractions in U-46619 precontracted isolated small PA (160-260 microns diameter) were significantly increased from 51 +/- 13 mg in the control group to 142 +/- 38 mg (P < or = 0.05) in AC animals. Nitro-L-arginine (NLA; 100 microM) contractions were also enhanced in the AC animal. The enhanced NLA response may correlate with an increase in endothelial cell NO synthase (NOS) as detected by Western blotting (132 +/- 28% of control; P < 0.05). These data suggest that, in this renin-dependent model of systemic hypertension, there is increased endothelial cell NOS activity that maintains low PA tone, preventing the lung from developing increased pressures.
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PMID:Peripheral hypertension and alterations in pulmonary vascular regulation. 925 47

This study assessed vasodilator responses in skeletal muscle resistance arteries (100-250 microns) from rats with chronic (4-8 wk) reduced renal mass (RRM) hypertension and normotensive sham-operated controls on a high (4% NaCl; HSSHAM)- or low (0.4% NaCl; LSSHAM)-salt diet. Arteries from RRM hypertensive rats [normal and high-salt diet (HSRRM)] and a separate group of spontaneously hypertensive rats exhibited an impaired dilation in response to reduced PO2 compared with those of their normotensive controls. Prostacyclin release, assessed by radio-immunoassay for 6-ketoprostaglandin F1 alpha, increased significantly in response to reduced PO2, but was unaffected by hypertension or salt intake. Dilator responses to acetylcholine and the prostacyclin analog iloprost were significantly reduced in both HSRRM and HSSHAM compared with LSSHAM rats. Dilation in response to direct activation of adenylate cyclase with forskolin or guanylate cyclase with the nitric oxide donor sodium nitroprusside was not significantly different in HSRRM, HSSHAM, and LSSHAM rats. These results indicate that hypoxic dilation is impaired in skeletal muscle resistance arteries of hypertensive rats and that chronic high-salt diet alone leads to impaired vasodilator responses in resistance arteries of normotensive animals, possibly via abnormalities in membrane function or G protein signaling rather than impaired second-messenger function.
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PMID:Response of resistance arteries to reduced PO2 and vasodilators during hypertension and elevated salt intake. 927 5

To investigate the activation of particulate guanylate cyclase in pregnant women with pregnancy-induced hypertension (PIH), plasma levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and guanosine 3',5'-cyclic phosphate (cGMP) were measured by radioimmunoassays specific to each substance. Ten normal nonpregnant women, and 30 normal pregnant women, 17 pregnant women with mild PIH and 11 pregnant women with severe PIH in the third trimester were included in this retrospective observational study. The diagnosis and classification of hypertension were carried out according to the technical bulletin (No. 91) of the American College of Obstetricians and Gynecologists. In the pregnant women with mild PIH, plasma cGMP levels as well as ANP and BNP levels were significantly (P < 0.05) higher than those in gestational age-matched normal pregnant or nonpregnant women. But in the pregnant women with severe PIH, plasma cGMP levels were significantly lower than those in pregnant women with mild PIH (P < 0.05), although plasma ANP and BNP levels were higher than those in pregnant women with mild PIH.
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PMID:Impaired guanosine 3',5'-cyclic phosphate production in severe pregnancy-induced hypertension with high plasma levels of atrial and brain natriuretic peptides. 927 14

Natriuretic peptide system consists of three endogenous ligands, ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide) and CNP (C-type natriuretic peptide), and three receptor subtypes, natriuretic peptide receptor (NPR)-A or guanylate cyclase (GC)-A and NPR-B or GC-B and C receptor (NPR-C). ANP and BNP are mainly secreted from the atrium and ventricle of the heart respectively to act as cardiac hormones whereas CNP is secreted from the endothelium to act as an endothelium-derived relaxing peptide. ANP and BNP regulate body fluid and blood pressure to reduce cardiac pre- and after-load. Recent molecular biology and developmental biotechnology demonstrated the physiological role of ANP and BNP for the determination of basal blood pressure. CNP can modulate the phenotype of vascular smooth muscle cells to regulate vascular remodeling. Therefore, natriuretic peptide system is implicated in the pathophysiology of hypertension, congestive heart failure atherosclerosis and renal diseases. Clinical application of natriuretic peptide system is actively going on progress. Determination of plasma ANP and BNP levels are useful for the evaluation of congestive heart failure, cardiac hypertrophy and acute myocardial infarction. Infusion of ANP improves acute heart failure. Application of NEP (neutral endopeptidase) inhibitor for the treatment of congestive heart failure and hypertension is under clinical trial.
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PMID:[Natriuretic peptide system]. 928 3

Human and rat plasma and rat hypothalamus contain a cytochemically detectable substance, the concentration of which rises with an increase in salt intake. The plasma concentration of this material is also raised in essential hypertension and in the spontaneously hypertensive rat (SHR), the Milan hypertensive rat, and the reduced renal mass (RRM) hypertensive rat. In the normal rat, the greatest concentration is found in the hypothalamus of the SHR and the RRM hypertensive rat. The physicochemical characteristics of this cytochemically detectable hypothalamic hypertensive factor (HHF), including chromatographic behavior and molecular weight range, suggest that it may share features common to a substituted guanidine that is present in established nitric oxide synthase (NOS) inhibitors. It was therefore decided to determine the effect on NOS activity of the HHF obtained from mature SHR. The ability of HHF to inhibit NOS activity was studied on (1) NOS extracted from bovine aorta, rat brain, and human platelets by measuring the conversion of radiolabeled L-arginine to L-citrulline and (2) rat liver NOS measured indirectly with a cytochemical technique based on the stimulation of soluble guanylate cyclase activity in hepatocytes by NO. HHF showed a biphasic inhibitory action on platelet NOS activity that was greater with HHF obtained from SHR than from Wistar-Kyoto rats. HHF also had a biphasic inhibitory effect on hepatocyte NOS activity that was more potent when obtained from SHR. It is proposed that the increase in HHF, a novel form of NOS inhibitor that is elevated in SHR, may be involved in the rise in arterial pressure.
Hypertension 1997 Dec
PMID:Hypothalamic hypertensive factor: an inhibitor of nitric oxide synthase activity. 940 72

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