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1. |
Dopamine /8‐Hydroxylase Deficiency A Genetic Disorder of Cardiovascular Regulation |
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Hypertension,
Volume 18,
Issue 1,
1991,
Page 1-8
David Robertson,
Virginia Haile,
Sharon Perry,
Rose Robertson,
John Phillips,
Italo Biaggioni,
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摘要:
Dopamine /3-hydroxyIase (DBH) deficiency is a genetic disorder in which affected patients cannot synthesize norepinephrine, epinephrine, and octopamine in either the central nervous system or the peripheral autonomic neurons. Dopamine acts as a false neurotransmitter in their noradrenergic neurons. Neonates with DBH deficiency have had episodic hypothermia, hypoglycemia, and hypotension, but survivors sometimes cope relatively well until late childhood when overwhelming orthostatic hypotension profoundly limits their activities. The hypotension may be so severe that clonic seizures supervene. Most currently recognized patients are young or middle-aged adults. The diagnosis is established by the observation of severe orthostatic hypotension in a patient whose plasma norepinephrine/dopamine ratio is much less than one.
ISSN:0194-911X
出版商:OVID
年代:1991
数据来源: OVID
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2. |
Heterogeneity of Renin Alleles in Outbred Dahl Salt‐Sensitive (Brookhaven) Rats |
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Hypertension,
Volume 18,
Issue 1,
1991,
Page 9-11
Brian O'Dowd,
John Rapp,
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摘要:
Selectively outbred Dahl salt-sensitive (DS) and salt-resistant (DR) rats were compared with the inbred Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats developed from the original Brookhaven stocks by J.P. Rapp. The animals were evaluated for genotype at the renin locus. The inbred strains are uniformly homozygous for their respective alleles, s in SS/Jr and r in SR/Jr. DR rats were also uniformly homozygous for the r renin allele. In DS rats, however, three renin alleles were segregating. In addition to the s and r alleles, a third allele, designated the z allele, was found. The gene frequencies in DS rats were 5=0.690, r=0.284, and z=0.026. Continued use of DS and DR rats in most experimental work is inappropriate because of genetic heterogeneity in the DS stock.
ISSN:0194-911X
出版商:OVID
年代:1991
数据来源: OVID
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3. |
Genetic Heterogeneity of the Spontaneously Hypertensive Rat |
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Hypertension,
Volume 18,
Issue 1,
1991,
Page 12-16
Toru Nabika,
Yasuo Nara,
Katsumi Dceda,
Jiro Endo,
Yukio Yamori,
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摘要:
We examined DNA fingerprints of the spontaneously hypertensive rat from Shimane Institute of Health Science, Izumo, Japan, including seven substrains that were separated in the early stages of the establishment of the stroke-prone spontaneously hypertensive rat, and compared their fingerprints with those of rats from other sources. Obtained DNA fingerprints revealed that, in both the stroke-resistant spontaneously hypertensive rat and the Wistar-Kyoto rat, there is a substantial genetic difference between the rats from the National Institutes of Health and from Shimane Institute of Health Science. By contrast, only a small genetic difference was observed either between the rats from the National Institutes of Health and Charles River Laboratories or among the substrains of the spontaneously hypertensive rat in the Shimane Institute of Health Science. Further, in the strains from the Shimane Institute of Health Science, there were fingerprinting bands that could distinguish either the Wistar-Kyoto rat from all the substrains of the spontaneously hypertensive rat or the stroke-prone from the stroke-resistant spontaneously hypertensive rat in spite of their close genetic backgrounds. From the observations above, we concluded 1) that there is substantial genetic variance of the spontaneously hypertensive rat between the two major sources in the world, the National Institutes of Health and the Shimane Institute of Health Science and 2) that by DNA fingerprinting analysis, it is possible to identify the restriction fragment length polymorphisms that are specific for the spontaneously hypertensive rat or the stroke-prone spontaneously hypertensive rat These polymorphisms can be applied in the segregation study of the F2 generation. {Hypertension 1991;18:12-16
ISSN:0194-911X
出版商:OVID
年代:1991
数据来源: OVID
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4. |
Reversal of Low Dose Angiotensin Hypertension by Angiotensin Receptor Antagonists |
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Hypertension,
Volume 18,
Issue 1,
1991,
Page 17-21
Glenn Smits,
John Koepke,
Edward Blaine,
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摘要:
During acute angiotensin II (Ang II) infusion (200 ng/kg/min i.v.) into anesthetized rats, mean arterial pressure rose from 124±1 to 154±2 mm Hg. The peptidic Ang n antagonist saralasin lowered arterial pressure in a dose-dependent manner. The maximal decrease in pressure was similar to that observed after the Ang II infusion was discontinued. The nonpeptide Ang II antagonist, 4'-{[2-butyl-4-chloro-5-(hydroxymethyl)-lff-imidazole-l-yl] methyi}[l,l'-biphenyl]-2- carboxylic add (SC-48742), lowered acutely elevated arterial pressure to a level similar to that on discontinuation of the angiotensin infusion. Chronic (8 days) infusion of Ang II (20 ng/kg/min i.v.) increased mean arterial pressure from 116±3 to 164±7 mm Hg, which then decreased to 121 ±6 mm Hg on termination of the infusion. Saralasin (10 ^tg/kg/min, a maximally effective dose during acute angiotensin infusion) decreased mean arterial pressure from 168±7 to 141±3 mm Hg, a pressure significantly higher (/?
ISSN:0194-911X
出版商:OVID
年代:1991
数据来源: OVID
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5. |
Ro 42‐5892 Is a Potent Orally Active Renin Inhibitor in Primates |
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Hypertension,
Volume 18,
Issue 1,
1991,
Page 22-31
Walter Fischli,
Jean-Paul Clozel,
Khalid El Amrani,
Wolfgang Wostl,
Werner Neidhart,
Heinz Stadler,
Quirico Branca,
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摘要:
The goal of the present study was to characterize the new renin inhibitor Ro 42-5892 in vitro and in vivo. In vitro, Ro 42-5892 inhibited purified human renin and human plasma renin specifically with an ICM of 0.7 nM and 0.8 nM, respectively. In vivo, Ro 42-5892 reduced mean arterial blood pressure in sodium-depleted marmosets and squirrel monkeys with as low a dose as 0.1 nig/kg orally. Higher doses reduced pressure by 30-35 mm Hg in both species. The duration of blood pressure decrease with 3 ing/kg orally was more than 24 hours. Maximal changes of plasma renin activity, immunoreactive angiotensin I, and immunoreactive angiotensin II were observed at 15 minutes. Renin was reduced by 74±31%, angiotensin I by 85±14%, angiotensin II by 89±17%, and immunoreactive active renin was increased by 70±39%. However, unlike pressure, these maximal effects were only transient with complete recovery of renin at 60 minutes under still reduced levels of angiotensin I (61 ±24%) and angiotensin II (71 ±38%) and increased concentrations of active renin (86±30%). The blood pressure lowering was due to specific renin inhibition as exemplified by the influence of the kidney, sodium status, species, or stereoselectivity. Moreover, the reduction of arterial blood pressure was similar to the action of the angiotensin converting enzyme inhibitor cilazapril and was not associated with reflex tachycardia in contrast to the pure vasodilator minoxidil. We conclude that Ro 42-5892 is a potent orally active renin inhibitor acting mainly by inhibition of renin in an extraplasmatic compartment
ISSN:0194-911X
出版商:OVID
年代:1991
数据来源: OVID
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6. |
Human Astrocytes Contain Two Distinct Angiotensin Receptor Subtypes |
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Hypertension,
Volume 18,
Issue 1,
1991,
Page 32-39
E. Tallant,
Neelam Jaiswal,
Debra Diz,
Carlos Ferrario,
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摘要:
The ability of angiotensin peptides to stimulate prostaglandin release and raise intracellular calcium levels by activating a phosphoinositide-specific phospholipase C was assessed in three human astrocytoma cell lines (CRTG3, STTG1, and VVITG2). The addition of angiotensin II to CRTG3 cells resulted in a dose-dependent release of prostaglandin E, and prostacyclin, the production of inositol 1,4,5-trisphosphate, and the mobilization of intracellular calcium. Angiotensin-(l-7), previously considered to be an inactive metabolite of angiotensin II, was as potent as angiotensin II for prostaglandin release but did not activate phospholipase C or mobilize intracellular calcium. In contrast, angiotensin-(2-8) caused only a slight increase in prostaglandin release, even though it was as effective as angiotensin II in augmenting inositol 1,4,5-trisphosphate production and calcium mobilization. Moreover, neither the release of prostaglandins in response to angiotensin II or angiotensin-(l-7) nor the mobilization of intracellular calcium in response to angiotensin II required extracellular calcium. Angiotensin II and angiotensin-(l-7) caused the release of prostaglandins from all three human astrocytoma cell lines, but changes in the level of intracellular calcium in response to angiotensin II only occurred in CRTG3 cells. Although previous studies have provided evidence for angiotensin receptor subtypes on the basis of selectivity of antagonists or signal transduction mechanisms, these data suggest that human astrocytes contain multiple angiotensin receptor subtypes on the basis of their response to different angiotensin heptapeptides ‐ angiotensin- (1-7) and angiotensin-(2-8). Furthermore, the data also suggest that preferential production of angiotensin-(1-7) and angiotensin-(2-8) may be one level of regulation whereby a particular signal transduction pathway [i.e., calcium mobilization by angiotensin-(2-8) or prostaglandin release by angiotensin-(l-7)] is selectively activated. {Hypertension 1991;18:32-39
ISSN:0194-911X
出版商:OVID
年代:1991
数据来源: OVID
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7. |
Attenuated Vascular Reactivity in Dogs With Anteroventral Third Ventricle Lesions |
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Hypertension,
Volume 18,
Issue 1,
1991,
Page 40-47
Jose Brum,
Alan Tramposch,
Christine Block,
Fawzy Estafanous,
Carlos Ferrario,
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摘要:
Lesion of the anteroventral portion of the third cerebral ventricle causes hypernatremia, adipsia, and attenuation of the pressor response to intravenous administration of angiotensin II and norepinephrine. In addition, these lesions prevent the development of several experimental models of hypertension. In this study, a lesion of the third cerebral ventricle region was made in 14 dogs. In seven dogs in which hypernatremia developed the lesions included the organum vasculosum of the lamina tenninalis; seven animals in which the circumventricnlar organ was spared by the lesion remained normonatremic Vascular responsiveness of isolated right carotid artery rings to angiotensin II and phenylephrine was assessed 3 days after lesioning the anteroventral portion of the third cerebral ventricle. In endothelium-denuded ring vessels, vasoconstrictor responses to phenylephrine were significantly decreased in animals both with and without inclusion of the organum vasculosum of the lamina tenninalis. A similar effect was observed in intact vessels of dogs in which the circumventricular organ was spared but not in those with lesions that included this area. In contrast, angiotensin Il-induced vasoconstriction was significantly decreased in the arteries with intact endothelium of both groups of lesioned animals. These data show that lesion of the anteroventral third ventricle area alters α-adrenergic and angiotensin II vascular responsiveness in isolated carotid artery rings with the possible participation of the endothelium.
ISSN:0194-911X
出版商:OVID
年代:1991
数据来源: OVID
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8. |
Cardiovascular Responses to Bicuculline in the Paraventricular Nucleus of the Rat |
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Hypertension,
Volume 18,
Issue 1,
1991,
Page 48-55
Douglas Martin,
Teodoro Segura,
Joseph Haywood,
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摘要:
The present study was undertaken to determine whether y-aminobutyric acid in the paraventricular nucleus contributes to the regulation of cardiovascular function. Blood pressure and heart rate were recorded and plasma catecholamines were measured in conscious rats receiving microinfusions of either artificial cerebrospinal fluid or a y-aminobutyric acid antagonist, bicuculline methiodide, bilaterally into the paraventricular nucleus. Artificial cerebrospinal fluid had no effect on any of the recorded variables. In contrast, infusion of bicuculline into the region of the paraventricular nucleus produced increases in blood pressure (20 ±2 mm Hg), heart rate (110±ll beats/min), and plasma concentrations of norepinephrine (640±107 pg/ml) and epinephrine (lt266±267 pg/ml). Pretreatment with a ganglionic blocking agent abolished both the blood pressure (-1±2 mm Hg) and heart rate (5±18 beats/min) effects. Bilateral adrenal medullectomy reduced the changes in plasma norepinephrine concentrations (81 ±14 pg/ml) significantly and abolished the changes in plasma epinephrine concentrations (5±4 pg/ml). Conversely, adrenal medullectomy reduced the pressor effects (18±2 mm Hg) only slightly while the heart rate responses were attenuated (42 ±9 beats/min) by approximately 50%. These results suggest that an endogenous y-aminobutyric acid system exerts a tonic inhibitory effect on the sympathetic nervous system at the level of the paraventricular nucleus of the hypothalamus.
ISSN:0194-911X
出版商:OVID
年代:1991
数据来源: OVID
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9. |
Does Regional Norepinephrine Spillover Represent Local Sympathetic Activity? |
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Hypertension,
Volume 18,
Issue 1,
1991,
Page 56-66
Peter Chang,
Eugene Kriek,
Jacques van der Krogt,
Peter van Brummelen,
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摘要:
Regional spillover of norepinephrine (NE), based on isotope dilution and single-compartment steady-state kinetics, is considered one of the best parameters for estimating organ sympathetic activity. However, the effects of local changes in clearance of NE on the spillover have not yet been investigated. We studied local NE kinetics and clearance in the forearm of 10 healthy subjects using intra-arterial infusions of NE, tritiated NE, the neuronal uptake inhibitor desipramine, and tyramine, which competes with NE for the neuronal uptake carrier. Before and during complete blockade of neuronal uptake by desipramine the venous concentrationtime curves for tritiated NE and for NE released by tyramine were biexponential, consistent with the presence of (at least) two compartments for circulating tritiated NE and for locally released NE. The time constants for tyramine-induced release of NE and, in the same subjects during desipramine infusion, for tritiated NE were almost equal at the same level of forearm blood flow. This argues against possible diffusion or transport differences for NE to and from the circulation and the synapse. The regional intrinsic clearance capacity (a measure of the maximal ability of an organ to irreversibly remove drug by all pathways in the absence of any flow limitations) for NE decreased in the forearm by 65% (p<0.01) during neuronal uptake blockade by desipramine; the forearm clearance decreased by 59% (p<0.001), whereas the spillover rate of NE increased from 33±5 to 63±11 pmol-min'1 (p<0.05). Nitroprussideinduced increments in blood flow increased the spillover of NE from 18±4 to 35±6 pmolmin"1 (/7
ISSN:0194-911X
出版商:OVID
年代:1991
数据来源: OVID
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10. |
Sodium and Volume Sensitivity of Blood Pressure Age and Pressure Change Over Time |
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Hypertension,
Volume 18,
Issue 1,
1991,
Page 67-71
Myron Weinberger,
Naomi Fineberg,
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摘要:
Salt sensitivity has been implicated in the age-related increase in blood pressure. We studied the reproducibility of a rapid method for assessing sodium sensitivity and resistance of blood pressure as well as the effect of age on this phenomenon. Blood pressure after volume expansion with 2 1 intravenous saline (0.9%) over 4 hours was compared with that after 1 day of 10 mmol sodium chloride intake and 3 and 40 mg oral doses of furosemide. Normal and hypertensive subjects (n=28) were studied twice within a year. Cross-sectional observations of the effect of age were made from studies in 230 hypertensive and 430 normotensive subjects. Longitudinal observations of blood pressure change over time were made 10 or more years after categorization of sodium responsivity in 31 subjects. The blood pressure response was reproducible in 28 subjects studied twice (r=0.56,p<0.002). Four subjects changed salt-responsiveness status and six were indeterminate on restudy. Sodium sensitivity of blood pressure increased significantly with increasing age in the entire population (n=660, r= ‐038,p<0.001). The relation was more striking in hypertensive subjects (n=230, r= -0.31,p<0.001) in whom a progressive increase in salt sensitivity with decades was seen than in the normotensive group (n=430, r=‐0.19, p<0.01) in whom salt sensitivity was not observed until the sixth decade. Salt-sensitive subjects had a significantly greater increase in systolic (p<0.001) and diastoiic (/?
ISSN:0194-911X
出版商:OVID
年代:1991
数据来源: OVID
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