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1. |
Elevated Serum Insulin Levels in Patients With Essential Hypertension and Microalbuminuria |
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Hypertension,
Volume 23,
Issue 6, Part 1,
1994,
Page 681-687
Stefano Bianchi,
Roberto Bigazzi,
Carla Valtriani,
Ivo Chiapponi,
Gianpaolo Sgherri,
Giorgio Baldari,
Andrea Natali,
Eleuterio Ferrannini,
Vito Campese,
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摘要:
Hyperinsulinemia, insulin resistance, or both have been described in patients with essential hypertension. Previous work from our laboratory has shown that in hypertensive patients with microalbuminuria, dyslipidemia and abnormal patterns in the diurnal variations of blood pressure are frequently associated. Whether hyperinsulinemia and microalbuminuria are directly related has not been determined. To test this possibility, we measured the plasma insulin response to an oral glucose load in 25 patients with or without microalbuminuria and 20 normotensive control subjects. Serum lipid profile and 24-hour ambulatory blood pressure were obtained. In the hypertensive patients as a group, the plasma insulin response to glucose (evaluated as the insulin area under the curve) was significantly enhanced compared with a group of 20 normotensive healthy control subjects (46 311±3745 and 27 557±2563 pmol/L×2 hours,P<.01). When the hypertensive patients were subdivided according to their albumin excretion rate, the microalbuminuric patients had significantly higher plasma glucose (969±45.2 versus 762±28.7 mmol/L×2 hours,P<.01) and insulin (59 172±5964 versus 37 737±3422 pmol/L×2 hours,P<.01) area under the curve values. In addition, a significant direct correlation was found to exist between insulin area under the curve and the urinary albumin excretion rate (r=.63,P<.001). Serum levels of lipoprotein(a) were significantly greater (P<.01) in patients with than in those without microalbuminuria and in control subjects. Furthermore, daytime diastolic blood pressure and nighttime systolic and diastolic blood pressure values were greater in patients with than in those without microalbuminuria. We conclude that in patients with essential hypertension microalbuminuria is associated with an enhanced insulin response to glucose, altered lipid levels, and an abnormal circadian blood pressure pattern, thereby forming a cluster with pathogenic potential for cardiovascular complications.
ISSN:0194-911X
出版商:OVID
年代:1994
数据来源: OVID
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2. |
Glucose and Insulin Levels During Diuretic Therapy in Hypertensive Men |
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Hypertension,
Volume 23,
Issue 6, Part 1,
1994,
Page 688-694
David Siegel,
Patricia Saliba,
Steven Haffner,
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摘要:
We investigated serum glucose and insulin levels resulting from thiazide or thiazide-like diuretic administration and determined whether they were associated with serum or intracellular potassium or magnesium values. We also explored the role of obesity both alone and with thiazides on serum insulin and glucose. Hypertensive men were withdrawn from diuretics and repleted with oral potassium and magnesium and then randomized to 2 months of treatment with (1) hydrochlorothiazide, (2) hydrochlorothiazide with oral potassium, (3) hydrochlorothiazide with oral potassium and magnesium, (4) hydrochlorothiazide and triamterene, (5) chlorthalidone, or (6) placebo. Serum was available from 202 participants for insulin and glucose determinations. Mean fasting serum glucose and insulin did not change significantly after 2 months of randomized therapy with the exception of participants randomized to chlorthalidone, who had significant increases in both serum insulin and glucose (P<.05 andP<.01, respectively). As body mass index increased, there was a corresponding increase in serum insulin and to a lesser degree in serum glucose. Also, as body mass index increased, participants taking hydrochlorothiazide had a corresponding increase of serum insulin (P<.05). After treatment, intracellular potassium and magnesium were both associated with higher serum insulin (P<.001 for each), and serum potassium was associated with higher and serum magnesium with lower serum glucose (P<.01 for each). In most hypertensive men, treatment with 50 mg chlorthalidone increases glucose and insulin levels, whereas administration of 50 mg hydrochlorothiazide, with or without potassium and/or magnesium conserving strategies, does not. Obesity has a deleterious effect on insulin metabolism both in hypertensive men not taking diuretics as well as in those receiving hydrochlorothiazide.
ISSN:0194-911X
出版商:OVID
年代:1994
数据来源: OVID
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3. |
Hypocalcemia and Pregnancy‐Induced Hypertension Produced by Low‐Calcium Diet |
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Hypertension,
Volume 23,
Issue 6, Part 1,
1994,
Page 695-702
Jorge Prada,
Reginald Tsang,
Kenneth Clark,
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摘要:
Recent studies from our laboratory in fasting pregnant ewes with twin gestation have implicated low serum calcium concentration in the etiology of hypertension in pregnancy. We hypothesized that the reduction in serum calcium concentration produced by feeding of a calcium-deficient diet in twin gestation would lead to a significant increase in maternal arterial blood pressure, vascular resistance, and protein in the urine and decreased uterine blood flow. Twenty-five instrumented ewes were used in the present study. After surgery a calcium-deficient diet and deionized water (calcium ion free) were provided ad libitum to 19 animals. Blood pressure, cardiac output, heart rate, and uterine blood flow were monitored every other day. Six control animals were provided with standard Rumilab diet and tap water (group 1). Animals on a lowcalcium diet (group 2) were subdivided according to the blood ionized calcium response to low dietary calcium intake. Nonhypocalcemic animals were assigned to group 2a (n=10), and hypocalcemic animals (calcium concentration below two standard deviations from the control group) were assigned to group 2b (n=9). In group 2b calcium concentration decreased from 1.03±0.04 mmol/L on day 110 of gestation to 0.77±0.03 mmol/L by day 125 of gestation. Arterial blood pressure increased significantly from 76±2 to 91±2 mm Hg, and uterine blood flow decreased from 950±53 to 579±48 mL/min. Urinary protein increased from 1.7±0.3 to 10.5±1.2g/L. Despite the fact that all animals in group 2 had the same low dietary calcium intake, group 2a did not develop hypocalcemia (by definition) or an increase in arterial blood pressure. The control group (n=6) showed no significant changes in the parameters studied. From these data we suggest that calcium plays a significant role in regulating systemic arterial blood pressure and uteroplacental blood flow in twin pregnant ewes.
ISSN:0194-911X
出版商:OVID
年代:1994
数据来源: OVID
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4. |
Blood Pressure Inversely Correlates With Thrombin‐Evoked Calcium Rise in Platelets |
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Hypertension,
Volume 23,
Issue 6, Part 1,
1994,
Page 703-709
Jeffrey Gardner,
Jwa-Hwa Cho,
Joan Skurnick,
Girgis Awad,
Michael Gutkin,
Lawrence Byrd,
Norman Lasker,
Abraham Aviv,
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摘要:
Earlier investigations showed a positive correlation between basal cytosolic free calcium in human platelets and blood pressure; however, recent studies have failed to show this relation. We undertook the present work to examine which platelet cytosolic calcium parameters (namely, cytosolic calcium in resting or stimulated states in calcium-containing and calcium-free media) present the least variability and best correlation with blood pressure. We studied 17 healthy white men on three different occasions separated by 1- and 4-week intervals. Their manual and ambulatory automated 24-hour blood pressure measurements were correlated with cytosolic calcium in resting and stimulated (thrombin-treated) fura 2-loaded platelets. The following cytosolic calcium parameters were measured in 1 mmol/L calcium and calcium-free media: basal cytosolic calcium, peak thrombin-evoked cytosolic calcium, and posttransient cytosolic calcium 5 minutes after thrombin treatment. The highest and lowest coefficients of variation were respectively shown by the basal cytosolic calcium (22.8%) and peak thrombin-evoked cytosolic calcium (10.1%) in calcium medium. Basal cytosolic calcium did not correlate with any of the blood pressure parameters. Of the cytosolic calcium parameters, peak thrombin-evoked cytosolic calcium in calcium medium demonstrated consistent (negative) correlations with blood pressure, with better correlations shown with diastolic than systolic blood pressure of both automated and manual blood pressure readings. Peak thrombin-evoked cytosolic calcium in calcium medium showed similar correlations with nighttime and daytime automated blood pressure measurements. There were no correlations between peak thrombin-evoked cytosolic calcium in calcium-free medium and blood pressure. However, the difference between peak thrombin-evoked cytosolic calcium in calcium and calcium-free media showed negative correlations with blood pressure. These findings indicate that basal cytosolic calcium in platelets correlates poorly with blood pressure. The inverse relation between peak thrombin-evoked cytosolic calcium increase and blood pressure suggests enhanced platelet calcium extrusion and/or sequestration capacity with increased blood pressure, probably reflecting an accelerated platelet calcium turnover rate with a higher blood pressure in vivo.
ISSN:0194-911X
出版商:OVID
年代:1994
数据来源: OVID
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5. |
Calcium Dependency of Frequency‐Stimulated Atrial Natriuretic Peptide Secretion |
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Hypertension,
Volume 23,
Issue 6, Part 1,
1994,
Page 710-716
Rick Schiebinger,
Yangfan Li,
Edward Cragoe,
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摘要:
In this study we examined the mechanism whereby atrial natriuretic peptide secretion is increased when the frequency of contraction is raised from 2 to 5 Hz. We tested the hypothesis that calcium plays a significant role in the frequency-stimulated response. Using superfused rat left atria, we found that lowering the superfusate calcium concentration from 1.8 to 0.2 mmol/L abolished the frequency-stimulated atrial natriuretic peptide secretory response. Superfusion with ryanodine (1 μmol/L), an inhibitor of sarcoplasmic reticulum calcium release, resulted in a minimal inhibitory effect. Superfusion with 50 μmol/L nitrendipine or 10 μmol/L diltiazem inhibited the frequency-stimulated response by 46% to 48%. The lack of total inhibition suggested that an additional mechanism of calcium influx was involved, namely, inward calcium movement carried by Na+-Ca2+exchange. As intracellular sodium has been reported to rise with an increase in beat frequency, a fall in the sodium gradient would favor inward calcium movement by Na+-Ca2+exchange. Because we could not directly assess the role of Na+-Ca2+exchange in this experimental paradigm, we examined the effect of lowering the transmembrane sodium gradient on atrial natriuretic peptide secretion by superfusion with the sodium channel activator veratridine or the sodium ionophore monensin. Superfusion with 1 μmol/L veratridine increased atrial natriuretic peptide secretion by 2.3-fold, and 1, 5, and 10 μmol/L monensin increased secretion by 1.1-, 2.1-, and 15.7-fold, respectively. In addition, we examined the possibility that the reported rise in intracellular sodium associated with increased beat frequency was due to enhanced Na+-H+antiporter activity. Superfusion with the Na+-H+antiporter inhibitor 5-(N,N-hexamethylene)- amiloride (25 μmol/L) abolished the frequency-stimulated secretory response. We conclude the following: (1) Frequencystimulated atrial natriuretic peptide secretion is dependent on calcium influx; (2) calcium influx through L-type calcium channels plays a significant role in the frequency-stimulated response; (3) by inference, Na+-Ca2+exchange is also an important mechanism of calcium influx; and (4) calcium release from the sarcoplasmic reticulum plays only a minor role in the frequency-stimulated response. These results lend further support to the concept that calcium is an important second messenger in regulated secretion of atrial natriuretic peptide.
ISSN:0194-911X
出版商:OVID
年代:1994
数据来源: OVID
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6. |
Glucose Intolerance as a Predictor of Hypertension in Pregnancy |
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Hypertension,
Volume 23,
Issue 6, Part 1,
1994,
Page 717-721
Caren Solomon,
Steven Graves,
Michael Greene,
Ellen Seely,
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摘要:
Insulin resistance is associated with and may be causal in essential hypertension, but the relation between insulin resistance and hypertension arising de novo in pregnancy is unclear. Transient hypertension of pregnancy (newonset nonproteinuric hypertension of late pregnancy) is associated with a high risk of later essential hypertension and thus may have similar pathophysiology. To assess the association between glucose intolerance and subsequent development of proteinuric and nonproteinuric hypertension in pregnancy in women without underlying essential hypertension or overt glucose intolerance, we performed a retrospective case-control study comparing glucose levels on routine screening for gestational diabetes mellitus among women subsequently developing hypertension. Women who developed hypertension in pregnancy (n=97) had significantly higher glucose levels on 50-g oral glucose loading test (P<.01) and a significantly higher frequency of abnormal glucose loading tests (≥7.8 mmol/L) (P<.01) than women who remained normotensive (n=77). Relative glucose intolerance was particularly common in women who developed nonproteinuric hypertension. Women who developed hypertension also had greater prepregnancy body mass index (P≤.0001) and baseline systolic and diastolic blood pressures (P≤.0001 for both), although all subjects were normotensive at baseline by study design. However, after adjustment for these and other potential confounders, an abnormal glucose loading test remained a significant predictor of development of hypertension (P<.05) and, specifically, nonproteinuric hypertension in pregnancy (P<.01). Among a subgroup of women in whom insulin levels were also measured (n=80), there was a nonsignificant trend toward higher insulin levels in women developing hypertension. These results suggest that relative glucose intolerance is associated with an increased risk of new-onset hypertension in pregnancy, particularly the nonproteinuric type, and indirectly support the hypothesis that insulin resistance may play a role in the pathogenesis of this disorder.
ISSN:0194-911X
出版商:OVID
年代:1994
数据来源: OVID
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7. |
Altered Protein Kinase C Regulation of Phosphoinositide‐Coupled Receptors in Deoxycorticosterone Acetate‐Salt Hypertensive Rats |
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Hypertension,
Volume 23,
Issue 6, Part 1,
1994,
Page 722-728
Angelino Calderone,
Laurence Oster,
Pierre Moreau,
Jean-Lucien Rouleau,
Duncan Stewart,
Jacques de Champlain,
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摘要:
This study examined the contribution of phosphatidylinositol metabolism and the efficacy of protein kinase C-mediated desensitization in the exaggerated alb-adrenergic receptor-mediated inositol phosphate response in the aorta of the deoxycorticosterone acetate (DOCA)-salt rat model of hypertension. The basal accumulation of inositol phosphates and the basal incorporation of [3H]myo-inositol in the phosphatidylinositol lipid pool were significantly higher in the aorta of these hypertensive rats. A positive correlation (r=.88,P<.01) was demonstrated between basal inositol phosphate levels and the [3H]myo-inositol-labeled phosphatidylinositol lipid pool. In hypertensive rats, α1b-adrenergic receptor-mediated inositol phosphate production in response to phenylephrine was significantly higher compared with normotensive rats. Despite the normalization of phenylephrine-mediated inositol phosphate production to the [3H]myo-inositol-labeled phosphatidylinositol lipid pool, the α1b-adrenergic response remained significantly higher in the hypertensive rats. Phorbol ester activation of protein kinase C attenuated to a lesser extent phenylephrinemediated inositol phosphate production (40%) in the aorta of hypertensive rats compared with the 80% attenuation observed in the aorta of normotensive rats. This desensitization was inhibited in both groups by the protein kinase C inhibitor staurosporine. The blunted desensitization of the α1b-adrenergic receptor by protein kinase C activation was not associated with a decrease in protein kinase C activity in the hypertensive rats, because aortic strips from these animals were more responsive to phorbol ester activation than aortic strips from normotensive animals. Moreover, the in vivo administration of staurosporine reduced mean arterial pressure to a greater extent in the hypertensive rats. In the same vascular tissue of these hypertensive rats, endothelin-1 receptor-mediated inositol phosphate production was significantly reduced, and in contrast to the nonnotensive rats, in which a 50% decrease was observed, the endothelin-1 receptor was unresponsive to protein kinase C-mediated desensitization. From these results one can conclude that during the development of DOCA-salt hypertension, an increase in both basal phosphatidylinositol turnover and alb-adrenergic receptor reactivity could contribute to an enhanced vascular smooth muscle tone. These observations provide further evidence for an important role of the sympathetic nervous system and for the existence of an impaired regulation of the alb-adrenergic reactivity of vascular tissues in the development and/or maintenance of hypertension in DOCA-salttreated rats.
ISSN:0194-911X
出版商:OVID
年代:1994
数据来源: OVID
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8. |
Body Mass Index and Associations of Sodium and Potassium With Blood Pressure in INTERSALT |
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Hypertension,
Volume 23,
Issue 6, Part 1,
1994,
Page 729-736
Alan Dyer,
Paul Elliott,
Martin Shipley,
Rose Stamler,
Jeremiah Stamler,
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摘要:
This report further examines the relation of body mass index (BMI) to associations of 24-hour urinary sodium, potassium, and sodium-potassium ratio with blood pressure in INTERSALT, a 52-center international study of electrolytes and blood pressure. Analyses without adjustment for BMI indicated average systolic pressure greater by 6.00 mm Hg per 100 mmol higher sodium and diastolic by 2.52 mm Hg. With adjustment for BMI, these values were reduced to 3.14 and 0.14 mm Hg, respectively. For the sodium-potassium ratio, blood pressure associations were stronger when not adjusted for BMI, and for potassium, adjustment generally had little effect. To explore possible interactions of these variables with BMI in relation to blood pressure, the 52 centers were divided into two groups of 26 based on whether the center median for BMI was less than or greater than or equal to 24.5 kg/m2, and individuals within each of the 52 centers were classified into lower- or higher-BMI groups based on individual BMI less than or greater than or equal to 24.1 kg/m2. Sodium and the sodium-potassium ratio were positively and significantly and potassium inversely and significantly related to systolic pressure in all four of these subgroups, and the sodium-potassium ratio and potassium were related to diastolic pressure in two and three subgroups, respectively. Electrolyte-blood pressure associations did not differ significantly between the two subgroups of centers or between the two subgroups based on individuals. Although these results indicate that adjustment for BMI has an important effect on INTERSALT associations of sodium and the sodium-potassium ratio with blood pressure and may represent an overadjustment, they also indicate that each of the three variables is related to blood pressure throughout the BMI range. Thus, they do not support the concept of important interactions of sodium and potassium with BMI in relation to blood pressure.
ISSN:0194-911X
出版商:OVID
年代:1994
数据来源: OVID
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9. |
Blood Pressure‐Lowering Effect of an Orally Active Vasopressin V1 Receptor Antagonist in Mineralocorticoid Hypertension in the Rat |
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Hypertension,
Volume 23,
Issue 6, Part 1,
1994,
Page 737-743
Louise Burrell,
Paddy Phillips,
J. Stephenson,
J. Risvanis,
K. Rolls,
C. Johnston,
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摘要:
We studied the contribution of vasopressin to the maintenance of high blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertension in the rat using the nonpeptide orally effective vasopressin VI receptor antagonist OPC-21268. Binding kinetic studies demonstrated that oral OPC-21268 (30 mg/kg) acted as a competitive antagonist at the vasopressin VI receptor in DOCA-salt and salt control rats. Basal mean intra-arterial blood pressure was 140±4 mmHg (n=12) in DOCA-salt rats compared with 111±2 mm Hg in salt control rats (n=18). Acute oral OPC-21268 (30 mg/kg) significantly (P<.01) reduced mean intra-arterial pressure in DOCA-salt hypertension, with an average maximal decrease of 24±3 mm Hg occurring at 2.5±0.7 hours after dosing. Systolic blood pressure (tail-cuff) in DOCA-salt rats was 178±2 mm Hg. Chronic oral OPC-21268 (30 mg/kg) twice daily for 7 days significantly (P<.01) reduced systolic blood pressure in DOCA-salt hypertension, with an average maximal decrease of 27±5 mm Hg. The antihypertensive effect was reversed 5 days after treatment with OPC-21268 was stopped. In water control rats basal systolic pressure (120±1 mm Hg, n=20) was unchanged by chronic oral OPC-21268 (30 mg/kg twice daily for 7 days), and this was confirmed by direct measurement of mean intra-arterial pressure. After chronic oral OPC-21268 (30 mg/kg twice daily for 7 days) hepatic VI receptor binding was significantly reduced for up to 10 hours (P<.05). The results of this study suggest that vasopressin does not play a major role in the regulation of normal blood pressure in the rat but support a role for vasopressin in the maintenance of mineralocorticoid hypertension in the rat. OPC-21268 may be of use in the treatment of hypertensive conditions associated with elevated vasopressin concentrations.
ISSN:0194-911X
出版商:OVID
年代:1994
数据来源: OVID
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10. |
Vascular Responsiveness to Nitric Oxide Synthesis Inhibition in Hypertensive Rats |
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Hypertension,
Volume 23,
Issue 6, Part 1,
1994,
Page 744-751
Michael Pucci,
Kathleen Miller,
Leslie Dick,
Hui Guan,
Lang Lin,
Alberto Nasjletti,
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摘要:
We contrasted in normotensive and hypertensive rats the effect of inhibition of nitric oxide synthesis on isometric tension development by aortic rings bathed in Krebs' bicarbonate buffer.NG-Nitro-L-arginine methyl ester (LNAME) (3×10−4mol/L) increased tension (82±11% of the response to 120 mmol/L potassium chloride) in rings of thoracic aorta taken from hypertensive rats 7 to 14 days after aortic coarctation, whereas rings of abdominal aorta from below the coarctation were unresponsive, as were rings of thoracic aorta from rats with deoxycorticosterone-salt-induced hypertension and from the corresponding normotensive controls of either model of hypertension. The contractile response to L-NAME in aortic rings of rats with aortic coarctation was reversed by L-arginine (1 mmol/L), attenuated by removal of the endothelium, and blunted by the protein kinase C inhibitor staurosporine but was unaffected by inhibition of cyclooxygenase, scavengers of superoxide anion, or blockade of receptors for angiotensin, norepinephrine, serotonin, or endothelin. In additional experiments we contrasted the effect of L-NAME (10 mg/kg IV) on the blood pressure of sham-operated rats and rats with aortic coarctation after pretreatment of animals in both groups with DuP 753 (30 mg/kg IV) to achieve blood pressure equalization. The pressor response to L-NAME was twofold greater in rats with aortic coarctation than in sham-operated controls. That pressor and aortic constrictor responsiveness to L-NAME are increased after aortic coarctation suggests that a mechanism of vasodilation, mediated by nitric oxide, is preferentially manifested in rats with aortic coarctation-induced hypertension.
ISSN:0194-911X
出版商:OVID
年代:1994
数据来源: OVID
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