bluuebunny/crossref_metadata_2025 huggingface dataset:
ET
A
Receptor Antagonist Prevents Blood Pressure Elevation and Vascular Remodeling in Aldosterone-Infused Rats
Authors: Park Jeong Bae , Schiffrin Ernesto L.
Published: June 2012

Abstract
—Increased endothelin-1 may be associated with elevation of blood pressure (BP) and promotion of vascular hypertrophy, especially in salt-sensitive hypertension. Mineralocorticoid hypertension has been associated with activation of the endothelin system. We evaluated whether in aldosterone-infused rats the selective endothelin type A receptor-antagonist BMS 182874 prevents BP elevation and vascular hypertrophy. Rats were infused with aldosterone (0.75 μg/h) subcutaneously via a mini-osmotic pump and were offered 1% NaCl in the drinking water±BMS 182874 (40 mg/kg in food) for 6 weeks. Systolic BP was monitored by the tail-cuff method, and vascular changes of mesenteric arteries were evaluated using a pressurized myograph. Aldosterone-infusion significantly increased BP to 151±7 mm Hg compared with controls (108±4 mm Hg,
P
<0.01). BMS 182874 normalized BP (117±4 mm Hg). Media cross-sectional area of aorta was significantly increased by aldosterone infusion (
P
<0.05), and BMS treatment normalized it (
P
<0.001). Aldosterone infusion increased media width and media-to-lumen ratio of mesenteric resistance arteries (17.6±0.4 μm and 7.5±0.4%) compared with controls (14.2±0.5 μm,
P
<0.01, and 5.9±0.1%,
P
<0.05). BMS 182874 normalized media and media-to-lumen ratio (15.1±0.6 μm and 5.7±0.1%, both
P
<0.01). In conclusion, the endothelin type A receptor antagonist attenuated BP elevation and prevented vascular remodeling or hypertrophy of aorta and mesenteric resistance arteries in aldosterone-infused rats. These results suggest a role for endothelin-1 in BP elevation and structural alterations of large and small vessels in aldosterone and salt-induced hypertension.
Studies in Hemodynamics and Hypertension
Authors: Freis Edward D.
Published: June 2012

This review covers a representative sampling of investigations in hemodynamics and hypertension performed by the author during the period from approximately 1945 to 1980. The hemodynamic studies included a description of changes associated with congestive heart failure and with acute myocardial infarction. These studies emphasized for the first time the importance of left ventricular afterload and of the mobilizable venous reservoir. Other hemodynamic studies included diverse subjects such as the first and only recordings of pulse waves in arteries as small as 200 γm in diameter, velocity differences between red blood cells and plasma, turbulent blood flow in the ascending aorta, increase in velocity of blood flow of leg veins under compression, rates of transcapillary flow of solutes in humans, and the first use of external arterial pulse wave recordings to assess vascular compliance. Pioneer studies in hypertension included the first use of an antihypertensive drug to treat malignant hypertension and the first report of the treatment of hypertension with a thiazide diuretic.
Renal Blood Flow Dynamics and Arterial Pressure Lability in the Conscious Rat
Authors: Pires Silene L.S. , Barrès Christian , Sassard Jean , Julien Claude
Published: June 2012

It is not known whether renal blood flow (RBF) is still autoregulated when the kidney is exposed to large transient blood pressure (BP) fluctuations such as those occurring spontaneously in conscious sinoaortic baroreceptor-denervated (SAD) rats. In this study, BP and RBF were simultaneously recorded in 8 SAD rats (2 weeks before study) and 8 baroreceptor-intact rats during ≈3 hours of spontaneous activity. The kidney used for RBF recordings was denervated to prevent the interference of changes in renal sympathetic tone with autoregulatory mechanisms. In intact rats, RBF variability (coefficient of variation 9.1±0.8%) was larger (
P
<0.02) than BP variability (5.9±0.2%). This was mainly because of slow changes in RBF that were unrelated to BP and also to a prominent oscillation of RBF of ≈0.25-Hz frequency. Autoregulatory patterns were identified at frequencies <0.1 Hz and provided a modest attenuation of BP fluctuations. In SAD rats, RBF variability (12.4±1.6%) was lower (
P
<0.02) than BP variability (18.2±1.1%). Autoregulation powerfully attenuated BP changes <0.1 Hz (normalized transfer gain 0.21±0.02 in the 0.0015- to 0.01-Hz frequency range) but at the expense of an oscillation located at ≈0.05 Hz that possibly reflected the operation of the tubuloglomerular feedback. Large transient hypertensive episodes were not translated into RBF changes in SAD rats. We conclude that autoregulatory mechanisms have an ample capacity to protect the kidney against spontaneous BP fluctuations in the conscious rat. This capacity is not fully used under normal conditions of low BP variability.
Expression Analysis Using Oligonucleotide Microarrays in Mice Lacking Bradykinin Type 2 Receptors
Authors: Monti Jan , Gross Volkmar , Luft Friedrich C. , Milia Anna Franca , Schulz Herbert , Dietz Rainer , Sharma Arya M. , Hübner Norbert
Published: June 2012

We recently conducted detailed cardiovascular and blood pressure-related phenotypic studies of mice lacking the bradykinin-B
2
receptor and were unable to identify a phenotype despite insensitivity to infused bradykinin. We therefore used oligonucleotide microarray analysis of some 12 000 genes and expressed sequence tags to identify molecular mechanisms that might be involved in compensating for the lack of a functional B
2
receptor in the kidneys of the mice. We identified 2 gene families that may have an impact on cardiovascular regulation and the bradykinin pathway. A water transport channel in the kidney, AQP4, was downregulated in the mice, whereas other members of the gene family did not show differences in expression levels. In addition, a number of serine proteases were upregulated in B
2
receptor-deficient mice. These genes are all located within a gene cluster on mouse chromosome 7. The findings were verified by an independent method. We suggest that microarray analysis has usefulness in elucidating otherwise unappreciated compensatory signaling pathways.
6-[
18
F]Fluorodopamine Positron Emission Tomographic (PET) Scanning for Diagnostic Localization of Pheochromocytoma
Authors: Pacak Karel , Eisenhofer Graeme , Carrasquillo Jorge A. , Chen Clara C. , Li Sheng-Ting , Goldstein David S.
Published: June 2012

The diagnosis and treatment of pheochromocytoma depend critically on effective means to localize the tumor. Computed tomography and magnetic resonance imaging have good sensitivity but poor specificity for detecting pheochromocytoma, and nuclear imaging approaches such as
131
I-metaiodobenzylguanidine scintigraphy have limited sensitivity. Here we report initial results using 6-[
18
F]fluorodopamine positron emission tomography (PET) scanning in the diagnostic localization of pheochromocytoma. Twenty-eight patients with known or clinically suspected pheochromocytoma underwent PET scanning after intravenous injection of 6-[
18
F]fluorodopamine. Of the 28 patients, 9 had surgical confirmation of the tumor, 8 had previously diagnosed metastatic pheochromocytoma, and 11 had plasma levels of metanephrines that were within normal limits. All 9 patients with surgically proven pheochromocytoma had abnormal 6-[
18
F]fluorodopamine PET scans that identified the tumors. All 8 patients with metastatic pheochromocytoma had extra-adrenal sites of 6-[
18
F]fluorodopamine-derived activity. Of the 11 patients with normal plasma levels of metanephrines, 9 had negative 6-[
18
F]fluorodopamine PET scans, 1 had extra-adrenal foci of 6-[
18
F]fluorodopamine-derived activity, and 1 had symmetric uptake of 6-[
18
F]fluorodopamine in the region of the adrenal glands. In patients with known disease, 6-[
18
F]fluorodopamine PET scanning can detect and localize pheochromocytomas with high sensitivity. In patients in whom the diagnosis of pheochromocytoma is considered but excluded because of negative plasma metanephrine results, 6-[
18
F]fluorodopamine PET scans are consistently negative. These findings justify a clinical trial of 6-[
18
F]fluorodopamine PET scanning as a diagnostic tool.
Hypertensive Nephrosclerosis as a Relevant Cause of Chronic Renal Failure
Authors: Caetano Edna Regina Silva Pereira , Zatz Roberto , Saldanha Luís Balthazar , Praxedes José Nery
Published: June 2012

It is currently unclear whether hypertensive nephrosclerosis (HN), usually diagnosed solely on clinical grounds, is a relevant cause of end-stage renal disease. We biopsied 81 hypertensive outpatients (blood pressure ≥160/95 mm Hg) with moderate renal insufficiency, who were referred to our service from 1988 to 1998. Patients with known causes of hypertension, systemic disorders, rheumatic disease, or nephrotic syndrome were excluded. In 65% of patients, HN was the sole histological abnormality associated with renal dysfunction. Benign nephrosclerosis (BN), defined as isolated arteriolar hyalinosis and/or intimal fibrosis, was found in 18 HN patients (22%), whereas malignant nephrosclerosis (MN), denoted mainly by myointimal cell proliferation, appeared in 35 HN patients (43%). Previously undiagnosed primary nephritis (PN) was found in 13 patients (16%), whereas focal and segmental glomerulosclerosis, which might be either primary or secondary to hypertension, appeared in 15 patients (19%). These findings suggest that HN, in both its BN and MN forms, can be a definite cause of chronic renal insufficiency and that a substantial fraction of patients with renal insufficiency and clinical diagnosis of HN may actually have PN.
Plasma Ouabain-Like Factor During Acute and Chronic Changes in Sodium Balance in Essential Hypertension
Authors: Manunta Paolo , Messaggio Elisabetta , Ballabeni Cinzia , Sciarrone Maria Teresa , Lanzani Chiara , Ferrandi Mara , Hamlyn John M. , Cusi Daniele , Galletti Ferruccio , Bianchi Giuseppe ,   for the Salt Sensitivity Study Group of the Italian Society of Hypertension
Published: June 2012

An ouabain-like factor has been implicated repeatedly in salt-sensitive hypertension as a natriuretic agent. However, the response of plasma ouabain-like factor to acute and chronic variation of body sodium is unclear. We studied 138 patients with essential hypertension who underwent an acute volume expansion/contraction maneuver (2 days) and 20 patients who entered a blind randomized crossover design involving chronically controlled sodium intake and depletion (170 to 70 mmol/d; 2 weeks each period). In both studies, plasma levels of ouabain-like factor were higher during sodium depletion (acute: 338.8±17.4 and 402.7±22.8 pmol/L for baseline and low sodium, respectively,
P
<0.01; chronic: 320.4±32.0 versus 481.0±48.1 pmol/L,
P
=0.01). No significant change in plasma ouabain-like factor was observed after a 2-hour saline infusion (333.4±23.9 pmol/L) or controlled sodium (402.1±34.9 pmol/L). When patients were divided into salt-sensitive or salt-resistant groups, no differences in plasma ouabain-like factor were observed in the 2 groups at baseline or in response to the 2 protocols: salt resistant (n=69, 340.1±25.9 pmol/L) versus salt sensitive (n=69, 337.4±23.6 pmol/L) and chronic salt resistant (n=11, 336.0±53.2) versus salt sensitive (n=9, 301.1±331.4 pmol/L). However, circulating ouabain-like factor was increased by sodium depletion in both groups. These results demonstrate that circulating ouabain-like factor is raised specifically by maneuvers that promote the loss of body sodium. Acute expansion of body fluids with isotonic saline is not a stimulus to plasma ouabain-like factor. Moreover, basal levels of plasma ouabain-like factor do not differ among patients with salt-sensitive or salt-resistant hypertension. Taken together, these new results suggest that ouabain-like factor is involved in the adaptation of humans to sodium depletion and argue against the hypothesis that ouabain-like factor is a natriuretic hormone.
Interaction of α
1
-Na,K-ATPase and Na,K,2Cl-Cotransporter Genes in Human Essential Hypertension
Authors: Glorioso Nicola , Filigheddu Fabiana , Troffa Chiara , Soro Aldo , Parpaglia Paolo Pinna , Tsikoudakis Aristides , Myers Richard H. , Herrera Victoria L.M. , Ruiz-Opazo Nelson
Published: June 2012

Essential hypertension is a common disease the genetic determinants of which have been difficult to unravel because of its clinical heterogeneity and complex, multifactorial, polygenic etiology. Based on our observations that α
1
-Na,K-ATPase (
ATP1A1
) and renal-specific, bumetanide-sensitive Na,K,2Cl-cotransporter (
NKCC2
) genes interactively increase susceptibility to hypertension in the Dahl salt-sensitive hypertensive (Dahl S) rat model, we investigated whether parallel molecular genetic mechanisms might exist in human essential hypertension in a relatively genetic homogeneous cohort in northern Sardinia. Putative
ATP1A1-NKCC2
gene interaction was tested by comparing hypertensive patients (blood pressure [BP] >165/95 mm Hg) with normotensive controls age >60 years with BP <140/85 mm Hg. Genotype analysis with microsatellite markers revealed conformation to Hardy-Weinberg proportions for 6 alleles of both
ATP1A1
(
D1S453
) and
NKCC2
(
NKCGT7
) markers, respectively. Two-by-six χ
2
analysis of alleles identified overrepresentation of
ATP1A1
No. 4 and
NKCC2
No. 4 alleles, respectively, in hypertensives compared with controls. With a qualitative trait framework, single-gene analysis detected association of both the
ATP1A1
No. 4 allele (
P
=0.004, χ
2
=8.094,
df
=1) and the
NKCC2
No. 4 allele (
P
=0.0002, χ
2
=14.279,
df
=1) with moderate to severe hypertension. Digenic analysis revealed that
ATP1A1
No. 4–
NKCC2
No. 4 allele interaction increases susceptibility to hypertension (
P
<0.0001, χ
2
=22.3,
df
=1) beyond levels obtained in single-gene analysis. Analysis was also performed in a quantitative trait framework with BP as the continuous trait parameter. Digenic analysis of
ATP1A1
No. 4–
NKCC2
No. 4 allele interaction revealed significant association with systolic (1-way ANOVA,
P
=0.000076) and diastolic (
P
=0.00099) BP. Interaction was corroborated by 2×2 factorial ANOVA for interaction (systolic BP interaction term,
P
<0.05, diastolic BP interaction term,
P
=0.035). The data are compelling that
ATP1A1
and
NKCC2
genes are candidate interacting hypertension-susceptibility loci in human essential hypertension and affirm gene interaction as an important genetic mechanism underlying hypertension susceptibility. Although corroboration in other cohorts and identification of functionally significant mutations are imperative next steps, the data provide a genotype-stratification scheme, with 4-fold predictive value (odds ratio, 4.28; 95% confidence interval, 2.29 to 8.0), which could help decipher the complex genetics of essential hypertension.
Effect of T-Type Selective Calcium Antagonist on Renal Microcirculation
Authors: Ozawa Yuri , Hayashi Koichi , Nagahama Takahiko , Fujiwara Keiji , Saruta Takao
Published: June 2012

Although calcium antagonists exert preferential vasodilation of renal afferent arterioles, we have recently demonstrated that nilvadipine and efonidipine, possessing both L-type and T-type calcium channel blocking action, reverse the angiotensin (Ang) II–induced afferent and efferent arteriolar constriction. In the present study, we investigated the role of T-type calcium channels in mediating the Ang II–induced efferent arteriolar tone using the selective T-type calcium channel blocker mibefradil. Isolated perfused hydronephrotic rat kidneys were used for direct visualization of renal microcirculation. Administration of Ang II (0.3 nmol/L) caused marked constriction of afferent (from 13.5±0.6 to 9.2±0.6 μm,
P
<0.01, n=6) and efferent (from 11.5±1.0 to 7.4±0.7 μm,
P
<0.01, n=5) arterioles. Mibefradil (1 μmol/L) dilated both vessels, with 82±11% and 72±7% reversal of afferent and efferent arterioles, respectively. Similarly, nickel chloride (100 μmol/L) caused dilation of both arterioles, similar in magnitude in afferent (68±10%, n=7) and efferent (80±7%, n=7) arterioles. To eliminate the possibility that the mibefradil-induced dilation was mediated by L-type channel blockade, mibefradil was administered in the presence of nifedipine (1 μmol/L). Thus, nifedipine caused modest efferent arteriolar dilation (30±6% reversal, n=9), and subsequent addition of mibefradil elicited further dilation of this vessel (80±4%,
P
<0.01 versus nifedipine). Furthermore, mibefradil reversed the Ang II–induced efferent arteriolar constriction even in the presence of nifedipine and phentolamine. These findings demonstrate that T-type calcium antagonists markedly dilate the Ang II–induced efferent arteriolar constriction, but the action is not mediated by inhibition of catecholamine release. This potent activity would contribute to the efferent arteriolar response to nilvadipine and efonidipine and may offer benefit in light of glomerular hemodynamics.
Nonendothelial NO Blunts Sympathetic Response of Normotensive Rats but not of SHR
Authors: Rabelo Fábio A.W. , Russo Eloísa M. , Salgado Maria Cristina O. , Coelho Eduardo B.
Published: June 2012

Abstract
—

— The inhibitory role of NO on sympathetic-induced contraction of resistance vessels of spontaneously hypertensive rats (SHR) has not been defined. Accordingly, we investigated the effect of endothelial removal or NO synthase inhibition on vasoconstrictor responses to sympathetic stimulation or phenylephrine in perfused mesenteric beds isolated from normotensive rats (NR) and SHR. Electrical stimulation (10 to 64 Hz) of perivascular nerves elicited a frequency-dependent increase in perfusion pressure that was greater in preparations from SHR (maximal effect: 223.4±8.4 versus 117.6±10.3 mm Hg in NR, n=6,
P
<0.001), and endothelium removal did not affect these responses in arteries from NR but caused a significant shift to the left of the frequency-response curve in arteries from SHR. In arteries with endothelium, inhibition of NO synthase with N
G
-nitro-
l
-arginine (L-NNA, 50 μmol/L) augmented the vasoconstrictor responses to sympathetic stimulation in both NR and SHR preparations. In preparations that had the endothelium removed, however, L-NNA potentiated only the responses to sympathetic stimulation of NR arteries. Vasoconstrictor responses to phenylephrine was potentiated by endothelium removal and in the presence of L-NNA only when the endothelium was intact in both NR and SHR arteries. The number of NADPH-diaphorase–positive cells in the superior mesenteric sympathetic ganglion of SHR was significantly less compared with that of NR. In conclusion, these data suggest a prejunctional inhibitory action of non–endothelial-derived NO, most probably neuronal-derived NO, on sympathetic-mediated vasoconstriction in NR arteries. In contrast, enhancement of the sympathetic-mediated vasoconstriction in SHR arteries elicited by L-NNA can be attributed to inhibition of endothelial-derived NO.
Induction of B
1
-Kinin Receptors in Vascular Smooth Muscle Cells: Cellular Mechanisms of MAP Kinase Activation
Authors: Christopher Julie , Velarde Victoria , Jaffa Ayad A.
Published: June 2012

Abstract
—

— Vascular smooth muscle cell (VSMC) proliferation is a prominent feature of the atherosclerotic process that occurs after endothelial injury. Although a vascular wall kallikrein-kinin system has been described, its contribution to vascular disease remains undefined. Because the B
1
-kinin receptor subtype (B1KR) is induced in VSMCs only in response to injury, we hypothesize that this receptor may be mediating critical events in the progression of vascular disease. In the present study, we provide evidence that des-Arg
9
-bradykinin (dABK) (10
−8
M), acting through B1KR, stimulates the phosphorylation of mitogen-activated protein kinase (MAPK) (p42
mapk
and p44
mapk
). Activation of MAPK by dABK is mediated via a cholera toxin–sensitive pathway and appears to involve protein kinase C, Src kinase, and MAPK kinase. These findings demonstrate that the activation of B1KR in VSMCs leads to the generation of second messengers that converge to activate MAPK and provide a rationale to investigate the mitogenic actions of dABK in vascular injury.
Interactions Between Angiotensin-(1-7), Kinins, and Angiotensin II in Kidney and Blood Vessels
Authors: Souza dos Santos Robson Augusto , Passaglio Kátia Tomagnini , Pesquero João Bosco , Bader Michael , Simões e Silva Ana Cristina
Published: June 2012

Abstract
—

— The heptapeptide angiotensin (Ang)-(1-7) is currently considered one of the biologically active end products of the renin-angiotensin system. The formation of Ang-(1-7) by pathways independent of Ang II generation, the selectivity of its actions, and its peculiar property of exhibiting effects that are partially opposite of those of the parent compound, Ang II, confer a unique biochemical and functional profile to this peptide. In this article, we will review novel aspects of the biological actions of Ang-(1-7), dealing with its interaction with Ang II and kinins, especially in the kidney and blood vessels.
Serum 18-Hydroxycortisol in Primary Aldosteronism, Hypertension, and Normotensives
Authors: Mosso Lorena , Gómez-Sánchez Celso E. , Foecking Mark F. , Fardella Carlos
Published: June 2012

Abstract
—

— This study reports the determination of plasma 18-hydroxycortisol (18-OHF) using a new and easy enzyme-linked immunosorbent assay (ELISA) method in primary aldosteronism and compares the values found in essential hypertensives and normotensive controls. In primary aldosteronism, we evaluated usefulness of plasma 18-OHF determination and the dexamethasone suppression test in the diagnosis of glucocorticoid-remediable aldosteronism using the genetic test as the gold standard. We studied 31 primary aldosteronism patients, 101 essential hypertensives, and 102 healthy normotensive controls. The plasma 18-OHF was measured using a biotin-avidin enzyme-linked assay by a new and purified polyclonal antibody. The 18-OHF value in primary aldosteronism was 6.3±8.05 nmol/L; this value is significantly higher than the value found in essential hypertensives and normotensive controls (2.81±1.42 and 2.70±1.41 nmol/L, respectively;
P
<0.0005). In primary aldosteronism, 4 of 31 patients had 18-OHF levels that were 10 times higher than the normal upper limit (2.983 nmol/L). The dexamethasone suppression test in primary aldosteronism patients was positive (serum aldosterone <4 ng/dL) in 13 of 31 cases. A chimeric
CYP11B1/CYP11B2
gene was demonstrated in 4 primary aldosteronism patients, corresponding to the same cases that had higher level of 18-OHF. In conclusion, plasma 18-OHF determination by this ELISA method is reliable for detecting glucocorticoid-remediable aldosteronism, and it does so better than the dexamethasone suppression test.
Pathophysiology of Hypertension During Preeclampsia Linking Placental Ischemia With Endothelial Dysfunction
Authors: Granger Joey P. , Alexander Barbara T. , Llinas Maria T. , Bennett William A. , Khalil Raouf A.
Published: June 2012

Abstract
—

— Studies over the past decade have provided a better understanding of the potential mechanisms responsible for the pathogenesis of preeclampsia. The initiating event in preeclampsia has been postulated to be reduced uteroplacental perfusion as a result of abnormal cytotrophoblast invasion of spiral arterioles. Placental ischemia is thought to lead to widespread activation/dysfunction of the maternal vascular endothelium that results in enhanced formation of endothelin and thromboxane, increased vascular sensitivity to angiotensin II, and decreased formation of vasodilators such as NO and prostacyclin. These endothelial abnormalities, in turn, cause hypertension by impairing renal-pressure natriuresis and increasing total peripheral resistance. The quantitative importance of the various endothelial and humoral factors in mediating the reduction in renal hemodynamic and excretory function and elevation in arterial pressure during preeclampsia are still unclear. Results from ongoing basic and clinical studies, however, should provide new and important information regarding the physiological mechanisms responsible for the elevation in arterial pressure in women with preeclampsia.
Time-Qualified Reference Values for Ambulatory Blood Pressure Monitoring in Pregnancy
Authors: Hermida Ramón C. , Ayala Diana E. , Mojón Artemio , Fernández José R.
Published: June 2012

Abstract
—

— To recognize the highly statistically significant circadian variability of blood pressure in pregnancy is to admit that the diagnosis of gestational hypertension or preeclampsia should be based not just on whether a casual blood pressure value is too high or too low, but rather on more pertinent questions: How long is blood pressure elevated above a given time-varying threshold? What is the excess blood pressure? When does most of the excess occur? Answers to these questions may be obtained by establishing (1) an adequate reference threshold for blood pressure and (2) a proper measurement of blood pressure elevation. Accordingly, we derived time-specified reference standards for blood pressure as a function of gestational age. We analyzed 1408 blood pressure series systematically sampled by ambulatory monitoring for 48 consecutive hours every 4 weeks from the first obstetric visit (usually within the first trimester of pregnancy) until delivery in 235 women with uncomplicated pregnancies. Data from each blood pressure series were synchronized according to the rest-activity cycle of each individual to avoid differences among women in actual times of daily activity. Data were then used to compute 90% circadian tolerance intervals for each trimester of pregnancy, in keeping with the trends in blood pressure along gestation previously documented. The method, derived on the basis of bootstrap techniques, does not need to assume normality or symmetry in the data, and therefore, it is highly appropriate to describe the circadian pattern of blood pressure variability. Results not only reflect expected changes in the tolerance limits as a function of gestational age, but also upper limits markedly below the thresholds currently used for diagnosing hypertension in pregnancy. The use of these time-qualified tolerance limits for the computation of a hyperbaric index as a measure of BP excess has already been show to provide high sensitivity and specificity in the early identification of gestational hypertension and preeclampsia.
Influence of Parity and Age on Ambulatory Monitored Blood Pressure During Pregnancy
Authors: Ayala Diana E. , Hermida Ramón C.
Published: June 2012

Abstract
—

— Studies based on casual blood pressure measurements concluded that both age and parity have significant effects on blood pressure during pregnancy. We have tested these results on clinically healthy normotensive women who were systematically studied by ambulatory blood pressure monitoring during their pregnancies. We analyzed 1254 blood pressure series sampled for 48 consecutive hours every 4 weeks from the first obstetric visit (usually within the first trimester of pregnancy) until delivery in 205 normotensive pregnant women. Data were divided for comparative analysis by parity (nulliparous versus multiparous), age (≤25, 26 to 30, 31 to 35, and ≥36 years), and trimester of gestation. Circadian parameters established by population multiple-component analysis were compared between groups with a nonparametric test. Effects of age and parity on blood pressure were also tested by ANOVA. A highly statistically significant circadian pattern described by a model that includes components with periods of 24 and 12 hours is demonstrated for systolic and diastolic blood pressure for all groups of pregnant women in all trimesters (always
P
<0.001). There was no significant difference in 24-hour mean among groups divided by parity at any age or stage of pregnancy (always
P
>0.160). A trend of increasing blood pressure with age was found for diastolic but not systolic blood pressure. Although statistically significant, differences in the 24-hour mean of diastolic blood pressure among groups divided by age were always <1.5 mm Hg. Data obtained from systematic ambulatory monitoring in normotensive pregnant women indicate the lack of differences in blood pressure according to parity. The small, although significant, increase in diastolic blood pressure with age may have little influence in the proper identification of women with gestational hypertension. Reference thresholds for blood pressure to be used in the early identification of hypertensive complications in pregnancy could thus be developed as a function of rest-activity cycle and gestational age, independent of parity or maternal age.
Renal response to propranolol treatment in hypertensive humans.
Authors: de Leeuw P W , Birkenhäger W H
Published: June 2012

To investigate the relationship between sympathetic activity and blood flow in the kidney during propranolol treatment, 55 patients with uncomplicated essential hypertension were studied. Twenty-five of them had been treated with propranolol (average daily dose 240 mg) for about two weeks; the others served as untreated controls. In all patients renal arteriography was carried out, after which renal plasma flow (125I-hippuran clearance), cortical blood flow (xenon-washout), and renal release of norepinephrine and renin were measured. In the propranolol group, renal plasma flow had also been determined before treatment. Cardiac output (dye-dilution) and creatinine clearance were measured both before as well as during therapy. In untreated hypertensives renal cortical blood flow was reduced to about 80% of what was predicted for the age level. On the basis of their changes in blood pressure, patients who were treated with propranolol were divided into responders (n = 15) and nonresponders (n = 10). Despite a similar fall in cardiac output in both subgroups, renal blood flow remained unchanged in responders, while it fell in nonresponders. In addition, renal norepinephrine release was significantly higher in nonresponders than in responders, while renin release in nonresponders was markedly suppressed. It may be concluded that sympathetic activity is an important determinant of renal (cortical) blood flow in essential hypertension. The effect of propranolol on the renal circulation depends, to some extent, on its unmasking of prevailing alpha-adrenergic tone. However, when blood pressure falls, an additional mechanism may be operative to cause renal vasodilation.
Sodium pump activity in arteries of rats with Goldblatt hypertension.
Authors: Overbeck H W , Grissette D E
Published: June 2012

Several laboratories have reported evidence suggesting abnormalities in the activity of the sarcolemmal sodium pump in vascular smooth muscle in hypertension. The present experiments were designed to investigate the relationship of such changes to the status of the renin-angiotensin-aldosterone system and body fluid volumes. We assessed sodium pump activity in vitro in sodium-loaded tail artery and thoracic aorta freshly excised from rats with chronic one-kidney, one clip, and two-kidney, one clip hypertension, and from appropriate normotensive control rats. 86Rb uptake in the absence (total uptake) and presence of 1.0 mM ouabain (ouabain-insensitive uptake) was measured, and ouabain-sensitive uptake (nmole/mg dry weight/18 min) was calculated. There were increases in plasma renin activity in the two-kidney, one clip rats only. In the hypertensive rats there were significant increases (up to +60%) in the ouabain-sensitive and total 86Rb uptakes in both tail artery and aorta. The magnitude of increases in arterial tissue uptakes in the two forms of Goldblatt hypertension, and in one-kidney, one clip hypertensive rats given 0.9% saline to drink for 2 to 3 days before sacrifice, were similar. Further sodium loading of aortas from normotensive control rats did not increase their uptake. The results of this study provide no evidence for decreases in sodium pump activity, instead indicating that there are increases in the activity of the pump in the sarcolemma or arterial smooth muscle studied in vitro. These increases in pump activity do not appear to be related to altered activity of the renin-angiotensin-aldosterone system, to changes in body fluid volumes, or to increases in intracellular concentrations of sodium. Increases in numbers or concentration of sarcolemmal pump molecules or in their turnover rate may be involved. However, in vitro 86Rb uptake by tail artery and aorta may not reflect the status of sodium pump activity in resistance vessels in vivo.
Carotid sinus baroreceptor control of arterial pressure in renovascular hypertensive subjects.
Authors: Mancia G , Ferrari A , Leonetti G , Pomidossi G , Zanchetti A
Published: June 2012

We used the neck chamber technique to study carotid baroreceptor control of blood pressure in 18 renovascular hypertensive subjects. Carotid baroreceptors were stimulated or deactivated for 2 minutes by applying graded reductions or increases in the neck tissue pressure (NTP) outside the carotid sinuses. The sensitivity of the baroreflex was separately calculated for these two conditions by the coefficients of the linear regressions relating the changes in NTP to the resulting changes in mean arterial pressure (MAP, catheter measurement). Baroreceptor deactivation increased MAP, and the sensitivity of the baroreflex was 0.12 /+- 0.07 in an early (5 to 1 seconds) and 0.32 /+- 0.05 in a late (90 to 120 seconds) phase of the stimulus application. Baroreceptor stimulation reduced MAP, and the baroreflex sensitivity was in this instance 0.66 /+- 0.08 and 0.05 /+- 0.08 respectively. Both these sensitivities were significantly greater than those obtained for the baroreceptor deactivation. These response entirely reproduced those of essential hypertensive subjects, but differed from those of normotensive subjects in whom baroreflex sensitivity was greater for carotid baroreceptor deactivation than for stimulation. Our findings indicate that carotid baroreceptor control of blood pressure undergoes a marked resetting in renovascular hypertension. The similarity of the baroreflex between renovascular and essential hypertension suggests as secondary origin of the resetting in man.
Prazosin plasma concentration and blood pressure reduction.
Authors: Larochelle P , du Souich P , Hamet P , Larocque P , Armstrong J
Published: June 2012

Prazosin was administered to 16 patients with essential hypertension in an initial dose of 0.5 mg, after which the blood pressure (BP), pulse, and plasma concentrations of prazosin were measured at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 24 hours. The dose of prazosin was then increased over 16 to 20 weeks, and similar sequences of measurements were obtained twice. Eleven patients completed the 20-week course. All patients did not respond in a similar way; two distinct patterns of BP and pulse response emerged, although there was no significant difference in the pharmacokinetic parameters, namely, absorption rate constant (Ka), maximum plasma concentration (Cpmax), time to reach the maximum concentration (Tmax), prazosin plasma half-life (T 1/2), elimination rate constant (kel), prazosin plasma concentration-time curve (AUC), and clearance. Patients in Group 1 had a marked reduction (52/30 mm Hg) of BP after the first dose of prazosin, no pulse increase, and needed a small dose of prazosin to maintain an adequate BP response. Patients in Group 3 had a minimal reduction in BP (14/13 mm Hg) after a first dose, a significant pulse increase, and needed a high dose of prazosin to control their BP. We conclude that this effect might be due to a different drug-receptor interaction, and the BP response and dose could be predicted from the response of the first dose of prazosin.
Role of angiotensinogen in blood pressure homeostasis.
Authors: Gardes J , Bouhnik J , Clauser E , Corvol P , Menard J
Published: June 2012

The role of angiotensinogen in blood pressure control was assessed in normotensive rats by observing the changes resulting from inhibition by specific rat angiotensinogen antiserum. The antiserum decreased blood pressure in rats on normal sodium as well as sodium-free diets (respectively delta BP = -30 +/- 6 mm Hg and -42 +/- 8 mm Hg). In binephrectomized sodium-replete rats, administration of antiserum did not reduce blood pressure, whereas in sodium-depleted animals it slightly decreased blood pressure by 11 +/- 3 mm Hg. These results suggest that angiotensinogen participates in the regulation of blood pressure in normotensive rats, even in the sodium-replete state.
Evidence for an enhanced transmembrane sodium (Na+) gradient induced by aldosterone in the incubated rat tail artery.
Authors: Friedman S M
Published: June 2012

Aldosterone is known to stimulate Na+ transport as measured in terms of current-carrying capacity of epithelial sheets or of Na+ - K+ ATPase activity in cells. The possibility that this is reflected in an altered steady-state transmembrane Na+ distribution in vascular smooth muscle was here examined directly. Transmembrane Na+ and K+ gradients were first dissipated by overnight incubation in K-free physiological salt solution (PSS) at 10 degrees C and then reestablished by 3 hours in normal PSS at 37 degrees C. The addition of d-aldosterone (but not corticosterone) to these media significantly reduced cell Na. This involved only free cell Na which was reduced by about 20% of 3 mmole/kg dry wt. No significant change in membrane permeability measured in terms of net Li uptake at 3 degrees C or at 37 degrees C was observed. The lowest effective aldosterone concentration was 2.8 x 10(-9) M. These results are consistent with the observed enhancement of net Na+ transport in incubated arteries in DOCA-induced hypertension and in the SHR but do not account for the increased Na+ permeability observed in these states.
Norepinephrine turnover in the cardiovascular tissues and brain stem of the rabbit during development of one-kidney and two-kidney Goldblatt hypertension.
Authors: Tanaka T , Seki A , Fujii J , Kurihara H , Ikeda M
Published: June 2012

To assess the role of the sympathetic and central noradrenergic neurons in one- and two- kidney Goldblatt hypertension, we examined the concentration and turnover of norepinephrine (NE) in the aorta, mesenteric artery, left ventricle, hypothalamus, midbrain, and pons medulla of hypertensive and control rabbits. Animals were made hypertensive by constriction of the left renal artery after right nephrectomy (1KGH group) or with the right kidney left intact (2KGH group), or were sham-operated on the renal artery (1KGC and 2KGC groups). At 14 days after the constriction, the blood pressure was increased to 136 +/- 3 mm Hg in the 1KGH vs 98 +/- 3 mm Hg in the 1KGC (p less than 0.001), and 136 +/- 2 mm Hg in the 2KGH vs 94 +/- 2 mm Hg in the 2KGC group (p less than 0.001). Turnover time in the aorta, mesenteric artery, and left ventricle in the 1KGH group was decreased to 47%, 45%, and 65% of that in the 1KGC group, respectively. Results suggest that enhanced sympathetic neuron activity in the cardiovascular system, especially in the arteries, contributes to the development of one-kidney Goldblatt hypertension. Norepinephrine turnover in the cardiovascular tissues in the 2KGH group and in the brain stem in the 1KGH and 2KGH group was not different from that in the control group.
Blood pressure, fatness, and fat patterning among USA adolescents from two ethnic groups.
Authors: Stallones L , Mueller W H , Christensen B L
Published: June 2012

Many studies have explored the relationship between blood pressure and body size and composition in adults and preadults, but none has inquired into the relationship of blood pressure and the anatomical distribution of subcutaneous fat (fat patterning). Fat patterning has an association with chronic diseases (diabetes and cardiovascular disease) in adults. We sought the relationship between fatness, fat patterning, weight, and height among adolescents (12 to 17 years of age) of two ethnic groups (black and white) from the Health Examination Survey. Systolic blood pressure adjusted for age was related to body build variables in all sex/ethnic groups in decreasing order of importance as follows: body weight (independent of height), fatness (as assessed by a two skinfold index), and an excess of fat on trunk relative to fat on the leg (pattern index). Neither fatness nor fat patterning was significantly related to blood pressure after weight entered the regression equation. Relative fat patterning may be less important in predicting cardiovascular risk factors in adolescents than it is in adults. The fact that body weight was more important than fatness suggests that the weight/blood pressure association is due to components of body mass other than body fat.
Plasma norepinephrine in the evaluation of baroreceptor function in humans.
Authors: Grossman S H , Davis D , Gunnells J C , Shand D G
Published: June 2012

The value of plasma norepinephrine measurement in assessing baroreceptor-mediated changes in sympathetic vasomotor activity was studied in seven healthy normotensive volunteers. Blood pressure was decreased by graded steady-state infusions of sodium nitroprusside (25-100 micrograms/min) and increased by infusions of phenylephrine (25-100 micrograms/min) at rates producing a 10% to 20% change in diastolic blood pressure. Sodium nitroprusside produced significant decreases in diastolic blood pressure (p less than 0.01) and calculated mean arterial blood pressure (p less than 0.005), and increases in heart rate (p less than 0.001) and plasma norepinephrine (p less than 0.001). Phenylephrine administration produced increases in systolic (p less than 0.005), diastolic (p less than 0.005), and mean blood pressure (p less than 0.001). Heart rate (p less than 0.001) and plasma norepinephrine (p less than 0.05) fell. The absolute changes in diastolic and mean pressure and heart rate were not significantly different for the two drugs, but were of opposite sign; however, the increase in plasma norepinephrine during hypotension was greater than the decrease during hypertension (p = 0.02). We conclude that plasma norepinephrine changes appropriately in response to altered blood pressure and that the response is greater to a given fall than to a rise in blood pressure, consistent with known changes in sympathetic vasomotor outflow.
Role of extracellular volume expansion in the development of DOC-salt hypertension in the rat.
Authors: Villamil M F , Amorena C , Ponce-Hornos J , Müller A , Taquini A C
Published: June 2012

Changes in inulin space, plasma and blood volume, exchangeable and "noninulin" sodium were studied during the prehypertensive, early and late hypertensive stages of deoxycorticosterone (DOC)-salt administration in the rat. The effect of an acute water load in previously nephrectomized animals was also studied. Hypertension developed after 1 to 2 weeks of the DOC-salt regimen and was always preceded by enlargement of the inulin space and increased plasma and blood volume. Expansion of extracellular fluids receded when blood pressure started to rise but reappeared after 4 to 6 weeks of treatment. Plasma sodium was high only in the hypertensive groups. An acute water load increased blood pressure of normal rats and decreased blood pressure of DOC-salt early hypertensive rats. These findings suggest that extracellular volume expansion inhibits a vasopressor mechanism that involves vasopressin and could be stimulated by hypernatremia.
Effect of colchicine on drug-induced changes in plasma renin concentration in rats.
Authors: Donoso V S , Bailie M D
Published: June 2012

Cytoplasmic microtubules appear to play a role in the secretion of a variety of protein and protein hormones. Involvement of microtubules in renin secretion has been hypothesized but not established. The present studies were designed to determine: 1) if the antimicrotubule drug, colchicine, would alter plasma renin concentration (PRC); and 2) if changes in PRC could be related to an effect on cytoplasmic microtubules. Dose response experiments in Sprague-Dawley rats showed that 0.4 or 0.8 mg/kg/day i.p. of colchicine for 3 days significantly increased PRC while a dose of 0.2 mg/kg/day was without effect. The increase in PRC at the higher doses was associated with toxicity of the drug. In other experiments, rats pretreated with colchicine (0.2 mg/kg/day) or saline received either furosemide (5 mg/kg) or isoproterenol (25 micrograms/rat) i.p. to stimulate renin secretion. Colchicine at a dose that did not alter basal PRC significantly inhibited an increase in PRC after stimulation with either isoproterenol or furosemide. Lumicolchicine, a structural isomer of colchicine without antimicrotubule activity, did not alter the response to isoproterenol stimulation. These data suggest that microtubules play a role in the increase in renin secretion following stimulation.
Type of obesity and blood pressure.
Authors: Berglund G , Ljungman S , Hartford M , Wilhelmsen L , Björntorp P
Published: June 2012

To explore the relationship between blood pressure on the one hand and body composition variables and fat cell size and number on the other, these factors were determined in a population sample (n = 120) of 49-year-old men with blood pressure (BP) ranging from very low to very high. BP increased linearly with body weight throughout the entire BP range, while body fat and fat cell size increased with increasing BP in the nonhypertensive but not in the hypertensive BP range. Body cell mass and fat cell number were unrelated to BP. Fat cell size (but not fat cell number) was positively correlated with most variables of glucose metabolism. It can be concluded that in normal men: the previously well-established relationship between body weight and BP is explained by an association between body fat and BP; BP is positively correlated with increased fat cell size, indicating hypertrophic obesity, while BP is unrelated to fat cell number; and increased fat cell size is associated with impaired glucose tolerance and hyperinsulinemia. The results point to the possibility that hypertrophic obesity and essential hypertension may be related to each other via common pathogenetic mechanisms.
Effects of moderate salt restriction on intralymphocytic sodium and pressor response to stress in borderline hypertension.
Authors: Ambrosioni E , Costa F V , Borghi C , Montebugnoli L , Giordani M F , Magnani B
Published: June 2012

The effects of a moderate dietary salt restriction on intralymphocytic sodium content and pressor response to stress (mental arithmetic, handgrip, and bicycle exercise) were tested in 25 young subjects with borderline hypertension. The study was performed by a randomized, cross-over, within-patient, experimental design. Diet did not significantly reduce blood pressure at rest but did so significantly in both systolic and diastolic blood pressure during stress and exercise. Variations in diastolic blood pressure induced by stimulation correlated significantly with intralymphocytic sodium content both before and during low-salt diet whereas no correlation was found in the case of systolic blood pressure and heart rate variations. These findings suggest that in young subjects with borderline hypertension, sodium homeostasis and blood pressure regulation are somehow interrelated, and that a moderate dietary salt restriction reduces both intralymphocytic sodium content and pressor response to adrenergic stimulation. This could be useful in preventing the development of sustained hypertension.