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1. |
Membrane Sodium‐Proton Exchange and Primary Hypertension |
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Hypertension,
Volume 21,
Issue 5,
1993,
Page 607-617
Dieter Rosskopf,
Rainer Düsing,
Winfried Siffert,
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摘要:
Recent studies have revealed that an enhancement of sodium-proton exchange is a frequently observed ion transport abnormality in essential hypertension. An altered antiport activity not only is measurable in blood cells of hypertensive subjects ex vivo but also is detectable in skeletal muscle in vivo. Several lines of argument suggest that the altered antiport activity is not an epiphenomenon of hypertension: 1) the increased activity is found only in a subgroup of patients with high blood pressure, 2) it is not tightly correlated to the severity or duration of hypertension, and 3) high sodium-proton exchange activity persists over time and is not affected by antihypertensive treatment. Available evidence suggests that enhanced sodium-proton exchange is associated with or a cause for the structural alterations found in resistance vessels of hypertensive individuals (media hypertrophy) and left ventricular hypertrophy. This review summarizes some of the physiological properties and roles of the sodium-proton exchanger and discusses its kinetic properties in essential hypertension. Furthermore, the reasons for the enhanced antiport activity and its potential implications regarding the pathogenesis of hypertension are discussed.
ISSN:0194-911X
出版商:OVID
年代:1993
数据来源: OVID
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2. |
Reflex Sympathetic Activation Induces Acute Insulin Resistance in the Human Forearm |
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Hypertension,
Volume 21,
Issue 5,
1993,
Page 618-623
Kenneth Jamerson,
Stevo Julius,
Thorkell Gudbrandsson,
Ove Andersson,
David Brant,
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摘要:
Inferences about the association between sympathetic overactivity and insulin resistance have been drawn from the infusion of sympathomimetic amines in supraphysiological doses. We used the isolated perfused human forearm to investigate the effect of reflex-induced sympathetic nervous system activation on the peripheral utilization of glucose in the skeletal muscles of 14 healthy men. Local hyperinsulinemia in the forearm (132±25 microunits/mL for 90 minutes) induced a significant increase in the utilization of glucose from baseline (16.4±3.1 mg · dL−1· min−1per 100 mL forearm volume) to a plateau (85.7±15.1 mg · dL−1· min−1per 100 mL forearm volume) between 40 and 60 minutes of insulin infusion but did not alter the utilization of oxygen. Reflex sympathetic nervous system activation was elicited by unloading of cardiopulmonary receptors with bilateral thigh cuff inflation to 40 mm Hg between 60 and 90 minutes of insulin infusion. Blood flow in the forearm was significantly decreased with inflation of thigh cuffs (average decrease of 19%,p<0.0001). As a result of thigh cuff inflation, there was a reduction in the utilization of glucose (a decrease of 23%,p<0.02), whereas oxygen utilization was unchanged. We find that an increase in sympathetic nervous system activation (within the normal range of physiological responses) can cause acute insulin resistance in the forearm of healthy volunteers. The reflex caused no change in oxygen utilization, but the same stimulus elicited a decrease in the utilization of glucose. The decrease in utilization of glucose in skeletal muscle may be caused by both the decrease in blood flow and by an adrenergic receptor-mediated resistance. The relative contributions of each of these mechanisms to insulin resistance deserves further investigation.
ISSN:0194-911X
出版商:OVID
年代:1993
数据来源: OVID
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3. |
Characteristics of Arterial Myosin in Experimental Renal Hypertension in the Dog |
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Hypertension,
Volume 21,
Issue 5,
1993,
Page 624-631
Aravinda Upadhya,
Mathew Samuel,
Robert Cox,
Roger Bagshaw,
Samuel Chacko,
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摘要:
We compared myosin samples isolated from iliac-femoral arteries of control and renal (stenosis) hypertensive dogs to determine the effects of increased blood pressure on the characteristics of the myosin. The ratio of 204-kd (SM-1) to 200-kd (SM-2) myosin heavy chains was approximately 1:0.75 for myosin from the iliac-femoral artery of normotensive dogs. This was not altered significantly in response to hypertension. Both SM-1 and SM-2 myosin heavy chains cross-reacted with antibody against smooth muscle myosin on Western blot analysis. In addition to these heavy chains, purified myosin from both groups showed a very faint protein band slightly below the 200-kd myosin heavy chain on electrophoresis on a highly porous sodium dodecyl sulfate-polyacrylamide gel. This protein band cross-reacted with antibody against nonmuscle myosin but not with smooth muscle myosin antibody. The 20- and 17-kd light chains of myosin isolated from normotensive and hypertensive dogs gave similar results on isoelectric focusing. Peptide maps of tryptic digests of heavy chains revealed both quantitative and qualitative differences. The Ca+2-activated myosin ATPase activity measured in high salt (0.5 mol/L KC1) was similar for myosin from both groups, whereas the potassium (ethylenedinitrilo)tetraacetic acid-stimulated ATPase of myosin from hypertensive animals was higher than that from normotensive animals. The actin-activated ATPase activities of the myosin from hypertensive animals was also higher than that of the myosin isolated from normotensive artery (0.11±0.007 and 0.213±0.008 μmol PIper milligram per minute, respectively, for normotensive and hypertensive). These studies indicate that the structural and functional properties of myosin in a muscular artery are altered in hypertensive dogs.
ISSN:0194-911X
出版商:OVID
年代:1993
数据来源: OVID
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4. |
Properties of the Random Zero Sphygmomanometer |
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Hypertension,
Volume 21,
Issue 5,
1993,
Page 632-637
Richard Kronmal,
Gale Rutan,
Teri Manolio,
Nemat Borhani,
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摘要:
The random zero sphygmomanometer is widely used in studies involving blood pressure measurement because it is believed to eliminate digit preference and reduce measurement error. We performed blood pressure measurements sequentially using random zero and standard sphygmomanometers in random order in 1,356 participants in the Cardiovascular Health Study. Despite adherence to the manufacturer's instructions, we observed a substantially nonuniform distribution of zero levels generated by the random zero sphygmomanometer and a disturbing correlation between the zero level and blood pressures taken with the standard sphygmomanometer. With the random zero device, the pooled estimated slopes for the regression of standard systolic and diastolic pressures on the zero level were −0.71 and −0.17, respectively (bothp<0.0001). The only plausible explanation for this relation between the random zero device and the standard device is that by some unknown mechanism the subject's blood pressure is influencing the zero level. Systolic and diastolic blood pressures measured with the random zero device were, respectively, 1.65 and 1.84 mm Hg lower (bothp<0.0001) than standard blood pressures. Digit preference was detectable in the uncorrected blood pressure and zero level measured with the random zero device but was eliminated after calculation of the corrected blood pressure. For most epidemiological studies, the random zero sphygmomanometer offers no significant advantage over the standard sphygmomanometer. It may still be useful in those epidemiological studies and clinical trials where blinding is important.
ISSN:0194-911X
出版商:OVID
年代:1993
数据来源: OVID
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5. |
Hydrochlorothiazide Improves Ventricular Compliance and Thus Performance Without Reducing Hypertrophy in Renal Artery Stenosis in Rats |
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Hypertension,
Volume 21,
Issue 5,
1993,
Page 638-645
Gavin Norton,
Oupa Tsotetsi,
Angela Woodiwiss,
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摘要:
The effect of hydrochlorothiazide (1 mg/kg per day) on left ventricular (LV) mass and systolic and diastolic function was investigated in two-kidney, one clip (2K1C) renovascular hypertensive rats. Hydrochlorothiazide was administered from 8 weeks, and LV mass and function were measured at 16 weeks after surgery to induce hypertension. Cardiac performance was determined from cardiac output, stroke volume (per 100 g of body weight), and stroke work (per gram of LV weight) versus LV end-diastolic pressure (LVEDP) and versus LV strain relations in anesthetized open-chest, ventilated rats. LV compliance was determined from the LVEDP versus strain relation. Strain was calculated from LV end-diastolic short-axis diameter values. Hydrochlorothiazide reduced systolic blood pressure in 2K1C rats to levels similar to those in sham-operated controls (sham) at 12 weeks after surgery. A reduced afterload failed to influence LV mass, as left LV hypertrophy developed to the same extent in treated 2K1C rats. 2K1C hypertension produced abnormal cardiac performance with altered cardiac output, stroke volume, and stroke work versus LVEDP relations (stroke work versus LVEDP, intercept of 2K1C versus sham,p<0.001). This was attributed to a decreased ventricular compliance (strain versus LVEDP, slope of 2K1C versus sham,p<0.001). In contrast, hydrochlorothiazide improved ventricular compliance (strain versus LVEDP, slope of 2K1C versus 2K1C hydrochlorothiazide,p<0.01) and thus returned the stroke work versus LVEDP relation to sham values (intercept of 2K1C versus 2K1C hydrochlorothiazide,p<0.001). We conclude that hydrochlorothiazide reduces blood pressure but not the development of ventricular hypertrophy in 2K1C rats. Although a reduced blood pressure did not produce regression of ventricular hypertrophy, it was associated with an improved ventricular compliance and thus performance. This study underscores the value of equating changes in ventricular hypertrophy with changes in cardiac function when the value of antihypertensive agents is being assessed.
ISSN:0194-911X
出版商:OVID
年代:1993
数据来源: OVID
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6. |
Elevated Hepatic Insulin Extraction in Essential Hypertension |
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Hypertension,
Volume 21,
Issue 5,
1993,
Page 646-653
Alexandra Kautzky-Willer,
Giovanni Pacini,
Michael Weissel,
Maria Capek,
Bernhard Ludvik,
Rudolf Prager,
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摘要:
Insulin resistance, hyperinsulinemia, and dyslipidemia are common characteristics of patients with untreated hypertension. However, the link between the vascular and metabolic disturbances is still unclear. To provide further insights into the metabolic picture of subjects with hypertension, we evaluated insulin resistance, pancreatic secretion, and hepatic extraction of the hormone in 16 untreated patients with essential hypertension before and after 12–16 weeks of drug treatment in comparison with 16 age-, sex-, and body weight-matched normotensive control subjects. All subjects underwent an oral and a frequently sampled intravenous glucose tolerance test. Metabolic parameters were calculated by the minimal model technique. The hypertensive patients exhibited a highly reduced tissue insulin sensitivity (2.6±0.4 versus 9.6±1.9 104min−1[microunits/mL];p<0.001). The basal secretion rate (70±11 versus 35±5 pmol/L per minute) and the total amount of prehepatically secreted insulin (32±4 versus 16±2 nmol/L in 4 hours) were significantly increased in the hypertensive patients compared with the control subjects (p<0.01), whereas the posthepatic insulin delivery rate was not significantly different between the two groups (4.9±0.6 versus 3.5±0.3 nmol/L in 4 hours). Hepatic insulin extraction was found to be significantly elevated in the hypertensive patients compared with control subjects (81±4% versus 69±3%,p<0.04). Increased hepatic insulin extraction partially ameliorated B cell hypersecretion in hypertensive patients. After 12–16 weeks of drug treatment, the blood pressure was normalized, but the metabolic profile of the patients remained unchanged. We conclude that elevated insulin extraction in the liver is a specific characteristic of individuals with essential hypertension and partially compensates pancreatic B cell hypersecretion.
ISSN:0194-911X
出版商:OVID
年代:1993
数据来源: OVID
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7. |
Epidermal Growth Factor Is a Potent Inhibitor of Renin Secretion |
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Hypertension,
Volume 21,
Issue 5,
1993,
Page 654-659
Indra Antonipillai,
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摘要:
Epidermal growth factor (EGF) is not only a cell mitogen but a potent vasoconstrictor that shares many properties with angiotensin II. Because EGF is localized in the kidney, we have studied the direct effects of EGF on renin secretion using both static incubations and perifusions of rat renal cortical slices. EGF at 5×10−9M significantly inhibited renin secretion in static incubations (control, 100±3%; EGF, 72±3%;p<0.001). When added to perifusions, EGF acted rapidly, reducing renin secretion at the earliest time period (10 minutes). Similarly, transforming growth factor-a, which can bind to the EGF receptor, also inhibited renin secretion (control, 92±8%; transforming growth factor-α [2×10−9M], 63±4%;p<0.02). Because both prostaglandins and lipoxygenase products of arachidonic acid have been shown to play a role in some EGF-mediated actions, we examined these possible mechanisms of EGF action. Meclofenamate, a cyclooxygenase blocker, and BW755c and baicalein, both lipoxygenase blockers, were studied. None of these agents altered EGF-mediated renin inhibition. EGF action has also been coupled to the stimulation of tyrosine kinase activity; therefore, we examined the effects of the tyrosine kinase inhibitors genistein and quercetin. Both genistein (10−5M) and quercetin (10−5M) abolished the inhibition of renin by EGF (control, 100±3%; EGF, 82±4%; EGF plus genistein, 110±7%;p<0.01; EGF, 75±4%; EGF plus quercetin, 92±4%;p<0.01). These results suggest that EGF is a potent inhibitor of renin release and that eicosanoids do not play a role in EGF action. However, blockade of tyrosine kinase activity prevents EGF inhibition of renin secretion. These studies support a potential paracrine role of EGF in renin secretion.
ISSN:0194-911X
出版商:OVID
年代:1993
数据来源: OVID
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8. |
Angiotensin Blockade Reverses Hypertension During Long‐term Nitric Oxide Synthase Inhibition |
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Hypertension,
Volume 21,
Issue 5,
1993,
Page 660-666
David Pollock,
James Polakowski,
Barbara Divish,
Terry Opgenorth,
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摘要:
Blockade of the renin-angiotensin system was studied in male Sprague-Dawley rats during long-term inhibition of nitric oxide synthase. Nitro-L-arginine-methyl ester (L-NAME) was placed in the drinking water for 4 weeks (∼ 100 nig/kg per day). Separate groups of rats were coadministered the angiotensin II antagonist A-81988 in the drinking water ranging from approximately 0.001 to 1 ing/kg per day. Control groups received only tap water or A-81988 alone. Each week, rats were placed in metabolic cages, and tail-cuff blood pressures and blood samples were taken. L-NAME produced a sustained elevation in tail-cuff pressure that was completely prevented by A-81988. No changes in creatinine clearance, sodium excretion, plasma creatinine concentration, or blood urea nitrogen were observed. Food and water intakes were identical in all groups. Water excretion was significantly increased in L-NAME-treated animals regardless of additional inhibitor treatment, suggesting a possible role for nitric oxide synthase in the control of water excretion; this effect was independent of blood pressure. Although less potent than A-81988, the angiotensin II antagonist losartan and the angiotensin converting enzyme inhibitor enalapril also blocked L-NAME-induced hypertension. In a separate series of experiments, rats were not given A-81988 until 2 weeks after hypertension had fully developed in L-NAME-treated rats. Within 1 week of treatment with the angiotensin II antagonist, tail-cuff pressure returned to normal. We conclude from these studies that long-term inhibition of endogenous nitric oxide production produces an angiotensin II-dependent form of hypertension.
ISSN:0194-911X
出版商:OVID
年代:1993
数据来源: OVID
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9. |
Leukocyte–Endothelial Cell Adhesion in Spontaneously Hypertensive and Normotensive Rats |
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Hypertension,
Volume 21,
Issue 5,
1993,
Page 667-673
Holger Arndt,
C. Smith,
D. Granger,
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摘要:
Although the etiology of hypertension-related organ damage remains poorly understood, it has recently been proposed that activated and adherent leukocytes may contribute to the pathogenesis of progressive organ injury in hypertension. The objective of this study was to determine whether the adherence and emigration of leukocytes in microvessels differ between spontaneously hypertensive and normotensive rats. Leukocyte adherence, rolling, and emigration as well as vessel diameter and erythrocyte velocity were monitored in mesenteric venules of age-matched normotensive and hypertensive rats. Measurements were obtained under baseline conditions and during superfusion of the mesentery with either platelet activating factor, leukotriene B4, orNG-nitro-L-arginine-methyl ester, an inhibitor of nitric oxide synthesis. Tissue-associated myeloperoxidase activity, an index of the total tissue granulocyte population, was measured in various tissues of normotensive and hypertensive rats. Systemic arterial pressure and the circulating polymorphonuclear leukocyte count were elevated in hypertensive relative to normotensive rats. The number of adherent and emigrated leukocytes under baseline conditions did not differ between normotensive and hypertensive rats. Although the nitric oxide synthase inhibitor caused a similar rise in leukocyte adherence and emigration in both rat strains, the adhesive interactions elicited by either platelet activating factor or leukotriene B4were significantly blunted in hypertensive relative to normotensive rats. Flow cytometric analysis of whole-blood samples revealed a lower surface expression of CD11b/CD18 on leukocytes from hypertensive rats under stimulated conditions. Myeloperoxidase activity in mesentery and small and large intestine was low, whereas lung, spleen, and stomach values were high in hypertensive compared with normotensive rats. These results indicate that the altered leukocyte distribution in spontaneously hypertensive rats may result from a reduced capacity for leukocytes to adhere and emigrate in response to endogenous inflammatory stimuli such as leukotriene B4and platelet activating factor.
ISSN:0194-911X
出版商:OVID
年代:1993
数据来源: OVID
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10. |
Catecholamine Secretory VesiclesAugmented Chromogranins and Amines in Secondary Hypertension |
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Hypertension,
Volume 21,
Issue 5,
1993,
Page 674-679
Marwan Takiyyuddin,
Luca De Nicola,
Francis Gabbai,
Thai Dinh,
Brian Kennedy,
Michael Ziegler,
Esther Sabban,
Robert Parmer,
Daniel O'Connor,
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摘要:
Chromogranins A and B are major soluble proteins in chromaffin granules. Their adrenomedullary content is increased in the spontaneously (genetic) hypertensive rat. Is augmented catecholamine vesicular storage of the chromogranins a specific feature of genetic hypertension? To explore this question, we measured chromogranin A immunoreactivity, using a novel, synthetic peptide radioimmunoassay, in rat adrenal medullas 4–6 weeks after induction of the two-kidney, one clip Goldblatt model of renovascular hypertension and in unmanipulated control animals. We also measured messenger RNAs of chromogranins A and B and dopamine β-hydroxylase by Northern blot. Immunoreactive adrenal chromogranin A was 3.3-fold higher (p<0.01) in clipped rat adrenals. Adrenal catecholamine concentrations and phenylethanoIamine-N-methyltransferase activity were also higher in clipped rats. Adrenal dopamine β-hydroxylase activity (both membrane-bound and soluble forms) and corticosterone (glucocorticoid) concentration did not significantly differ between the groups. Adrenal medullary chromogranin A messenger RNA levels in clipped rats were 3.2-fold higher (p=0.029) than those in the control group, and chromogranin B messenger RNA levels were 4.6-fold higher (p=0.05). Dopamine β-hydroxylase messenger RNA levels were 2.9-fold higher (p=0.038). Thus, augmented synthesis and storage of adrenomedullary chromogranins A and B, catecholamines, and their biosynthetic enzymes appear to be characteristic of both acquired and genetic hypertension.
ISSN:0194-911X
出版商:OVID
年代:1993
数据来源: OVID
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