bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Sodium Channel γ-Subunit Promoter Variant With Blood Pressure
Authors: Iwai Naoharu , Baba Shunroku , Mannami Toshifumi , Katsuya Tomohiro , Higaki Jitsuo , Ogihara Toshio , Ogata Jun
Published: June 2012

The
SCNN1G
gene, located on human chromosome 16p12, encodes the γ subunit of the amiloride-sensitive epithelial sodium channel, and mutations in
SCNN1G
can result in Liddle’s syndrome or pseudohypoaldosteronism type I. We identified sequence variations in the promoter region of
SCNN1G
and examined the association between this polymorphism and blood pressure in a large cohort (n=4075) representing the general population in Japan. We found
T(
−
1290)C
,
T(
−
501)G
,
G(
−
173)A
, and
G(
−
104)T
polymorphisms in the promoter region of
SCNN1G
and confirmed the existence of
T387C
and
T474C
polymorphisms in exon 3 and the
C1947G
polymorphism in exon 13. Because the genotypes of the
T(
−
1290)C
,
T(
−
501)G
,
G(
−
104)T
, and
T474C
polymorphisms were in tight linkage disequilibrium, we selected the
T474C
and
G(
−
173)A
polymorphisms for an association study. The
G(
−
173)A
polymorphism of
SCNN1G
had a significant effect on systolic pressure (
P
=0.0050) and pulse pressure (
P
=0.0050). The
AA
genotype was associated with an 11 mm Hg drop in systolic pressure and an 8 mm Hg drop in pulse pressure and with a higher prevalence of hypotension (
P
=0.0195). A transient transfection assay using MDCK cells and human renal epithelial cells indicated that the promoter activity of the
G(
−
173)
allele was higher than that of the
A(
−
173)
allele. Although the effects of the
A(
−
173)
allele were recessive and although the
AA
genotype was found in just 0.7% of our study population, we observed that this variation of human
SCNN1G
had significant effects on blood pressure.
Bradykinin Potentiation by Angiotensin-(1-7) and ACE Inhibitors Correlates With ACE C- and N-Domain Blockade
Authors: Tom Beril , de Vries René , Saxena Pramod R. , Danser A.H. Jan
Published: June 2012

ACE inhibitors block B
2
receptor desensitization, thereby potentiating bradykinin beyond blocking its hydrolysis. Angiotensin (Ang)-(1-7) also acts as an ACE inhibitor and, in addition, may stimulate bradykinin release via angiotensin II type 2 receptors. In this study we compared the bradykinin-potentiating effects of Ang-(1-7), quinaprilat, and captopril. Porcine coronary arteries, obtained from 32 pigs, were mounted in organ baths, preconstricted with prostaglandin F
2α
, and exposed to quinaprilat, captopril, Ang-(1-7), and/or bradykinin. Bradykinin induced complete relaxation (pEC
50
=8.11±0.07, mean±SEM), whereas quinaprilat, captopril, and Ang-(1-7) alone were without effect. Quinaprilat shifted the bradykinin curve to the left in a biphasic manner: a 5-fold shift at concentrations that specifically block the C-domain (0.1 to 1 nmol/L) and a 10-fold shift at concentrations that block both domains. Captopril and Ang-(1-7) monophasically shifted the bradykinin curve to the left, by a factor of 10 and 5, respectively. A 5-fold shift was also observed when Ang-(1-7) was combined with 0.1 nmol/L quinaprilat. Repeated exposure of porcine coronary arteries to 0.1 μmol/L bradykinin induced B
2
receptor desensitization. The addition of 10 μmol/L quinaprilat or Ang-(1-7) to the bath, at a time when bradykinin alone was no longer able to induce relaxation, fully restored the relaxant effects of bradykinin. Angiotensin II type 1 or 2 receptor blockade did not affect any of the observed effects of Ang-(1-7). In conclusion, Ang-(1-7), like quinaprilat and captopril, potentiates bradykinin by acting as an ACE inhibitor. Bradykinin potentiation is maximal when both the ACE C- and N-terminal domains are inhibited. The inhibitory effects of Ang-(1-7) are limited to the ACE C-domain, raising the possibility that Ang-(1-7) synergistically increases the blood pressure-lowering effects of N-domain-specific ACE inhibitors.
Wine Polyphenols Decrease Blood Pressure, Improve NO Vasodilatation, and Induce Gene Expression
Authors: Diebolt Myriam , Bucher Bernard , Andriantsitohaina Ramaroson
Published: June 2012

The effects of short-term oral administration of red wine polyphenolic compounds on hemodynamic parameters and on vascular reactivity were investigated in rats. Endothelial function and vascular smooth muscle contractility were studied in association with the induction of gene expression in the vascular wall. Rats were treated daily for 7 days by intragastric administration of either 5% glucose or red wine polyphenolic compounds (20 mg/kg). Administration of these compounds produced a progressive decrease in systolic blood pressure, which became significantly different on day 4. Aortas from rats treated with red wine polyphenolic compounds displayed increased endothelium-dependent relaxation to acetylcholine that was related to increased endothelial NO activity and involved a mechanism sensitive to superoxide anion scavengers. However, no increase in whole-body oxidative stress has been observed in rats treated with red wine polyphenolic compounds, as shown by plasma glutathione assay. Also, in the aorta, red wine polyphenolic compounds increased the expression of cyclooxygenase-2 and increased the release of endothelial thromboxane A
2
, which compensated for the extraendothelial NO–induced hyporeactivity in response to norepinephrine, resulting from enhanced inducible NO synthase expression. The present study provides evidence that short-term oral administration of red wine polyphenolic compounds produces a decrease in blood pressure in normotensive rats. This hemodynamic effect was associated with an enhanced endothelium-dependent relaxation and an induction of gene expression (of inducible NO synthase and cyclooxygenase-2) within the arterial wall, which together maintain unchanged agonist-induced contractility. These effects of red wine polyphenolic compounds may be a potential mechanism for preventing cardiovascular diseases.
Impaired Skin Capillary Recruitment in Essential Hypertension Is Caused by Both Functional and Structural Capillary Rarefaction
Authors: Serné Erik H. , Gans Reinold O.B. , ter Maaten Jan C. , Tangelder Geert-Jan , Donker Ab J.M. , Stehouwer Coen D.A.
Published: June 2012

Capillary rarefaction occurs in many tissues in patients with essential hypertension and may contribute to an increased vascular resistance and impaired muscle metabolism. Rarefaction may be caused by a structural (anatomic) absence of capillaries, functional nonperfusion, or both. The aim of this study was to assess the extent of structural versus functional capillary rarefaction in the skin of subjects with essential hypertension. We examined skin capillary density with video microscopy before and during maximization of the number of perfused capillaries by venous congestion (structural capillary number) and before and during postocclusive reactive hyperemia (capillary recruitment, which may have a structural and/or functional basis). The study group was composed of 26 patients with never-treated essential hypertension and 26 normotensive control subjects. In both groups, intermittently perfused capillaries in the resting state were an important functional reserve for recruitment during postocclusive hyperemia. Recruitment of perfused capillaries during postocclusive reactive hyperemia was decreased in the hypertensive subjects compared with normotensive control subjects (47.9±6.8 versus 55.3±8.2 capillaries/mm
2
, respectively;
P
<0.01). During venous occlusion, maximal capillary density was significantly lower in the hypertensive subjects than in the control subjects (52.5±6.6 versus 57.2±8.6 capillaries/mm
2
, respectively;
P
<0.05), suggesting structural rarefaction. However, in the hypertensive subjects compared with the normotensive subjects, a smaller proportion of the maximal number of capillaries was perfused during postocclusive hyperemia (91.6±7.5% versus 97.2±2.7%, respectively;
P
<0.05), suggesting an additional functional impairment of capillary recruitment. If the difference in capillary numbers during venous congestion (≈4.6 capillaries/mm
2
) truly reflects the structural difference between the normotensive and hypertensive subjects, then, at most, 62% (4.6/7.4×100%) of the difference in capillary numbers during postocclusive hyperemia (≈7.4 capillaries/mm
2
) can be explained by structural defects, and at least 38% can be explained by functional defects. In conclusion, in patients with essential hypertension, recruitment of perfused capillaries is impaired, which can be explained by both functional and structural rarefaction.
Renin Uptake by the Endothelium Mediates Vascular Angiotensin Formation
Authors: Hilgers Karl F. , Veelken Roland , Müller Dominik N. , Kohler Hans , Hartner Andrea , Botkin Suzanne R. , Stumpf Christian , Schmieder Roland E. , Gomez R. Ariel
Published: June 2012

We investigated the role of the vascular endothelium in the local production of angiotensin. Angiotensin release from isolated rat hindquarters perfused with an artificial medium was measured by high-performance liquid chromatography and radioimmunoassay. Perfused hindquarters with endothelium released angiotensin I spontaneously, indicating ongoing renin-angiotensinogen reaction. Endothelium denudation (by a detergent, validated by electron microscopy and by the absence of a vasodilator response to acetylcholine) reduced angiotensin I release by >90%, whereas bilateral nephrectomy 24 hours before perfusion abolished the release completely. Infusion of renin into perfused hindquarters induced sustained local angiotensin I release in the presence of an intact endothelium but not after endothelium denudation. The conversion of angiotensin I to angiotensin II was abrogated by endothelium denudation, whereas the disappearance of angiotensin II was unchanged. Endothelium denudation diminished the pressor response to angiotensin II but abolished the response to renin and angiotensin I. Expression of renin messenger RNA, investigated by reverse-transcription polymerase chain reaction using 4 different primer combinations, was not detected in up to 5 μg vascular RNA, whereas a renin signal was readily detected with 5 ng kidney RNA. The effects of endothelium destruction on Ang I formation support the notion that the endothelium mediates vascular angiotensin formation by taking up renin.
Differential Subcellular Actions of ACE Inhibitors and AT
1
Receptor Antagonists on Cardiac Remodeling Induced by Chronic Inhibition of NO Synthesis in Rats
Authors: Sanada Shoji , Kitakaze Masafumi , Node Koichi , Takashima Seiji , Ogai Akiko , Asanuma Hiroshi , Sakata Yasuhiko , Asakura Masanori , Ogita Hisakazu , Liao Yulin , Fukushima Tomi , Yamada Junko , Minamino Tetsuo , Kuzuya Tsunehiko , Hori Masatsugu
Published: June 2012

Chronic inhibition of NO synthesis induces cardiac hypertrophy independent of systemic blood pressure (SBP) by increasing protein synthesis in vivo. We examined whether ACE inhibitors (ACEIs) enalapril and temocapril and angiotensin II type-I receptor antagonists (angiotensin receptor blockers [ARBs]) losartan and CS-866 can block cardiac hypertrophy and whether changes in activation of 70-kDa S6 kinase (p70S6K) or extracellular signal–regulated protein kinase (ERK) are involved. The following 13 groups were studied: untreated Wistar-Kyoto rats and rats treated with NO synthase inhibitor
Nω
-nitro-
l
-arginine methyl ester (L-NAME), D-NAME (the inactive isomer of L-NAME), L-NAME plus hydralazine, L-NAME plus enalapril (3 mg · kg
−1
· d
−1
) or temocapril (1 or 10 mg · kg
−1
· d
−1
), L-NAME plus losartan (10 mg · kg
−1
· d
−1
) or CS-866 (1 or 10 mg · kg
−1
· d
−1
), L-NAME plus temocapril-CS866 in combination (1 or 10 mg · kg
−1
· d
−1
), and L-NAME plus rapamycin (0.5 mg · kg
−1
· d
−1
). After 8 weeks of each experiment, ratios of coronary wall to lumen (wall/lumen) and left ventricular weight to body weight (LVW/BW) were quantified. L-NAME increased SBP, wall/lumen, and LVW/BW compared with that of control. ACEIs, ARBs, and hydralazine equally canceled the increase in SBP induced by L-NAME. However, ACEIs and ARBs equally (but not hydralazine) attenuated increase in wall/lumen and LVW/BW induced by L-NAME. The L-NAME group showed both p70S6K and ERK activation in myocardium (2.2-fold and 1.8-fold versus control, respectively). ACEIs inactivated p70S6K and ARBs inactivated ERK in myocardium, but hydralazine did not change activation of either kinase. Thus, ACEIs and ARBs modulate different intracellular signaling pathways, inhibiting p70S6K or ERK, respectively, to elicit equal reduction of cardiac hypertrophy induced by chronic inhibition of NO synthesis in vivo.
Aortic Stiffness Is Associated With Visceral Adiposity in Older Adults Enrolled in the Study of Health, Aging, and Body Composition
Authors: Sutton-Tyrrell Kim , Newman Anne , Simonsick Eleanor M. , Havlik Richard , Pahor Marco , Lakatta Edward , Spurgeon Harold , Vaitkevicius Peter ,   for the Health ABC Investigators
Published: June 2012

The central arteries stiffen with age, causing hemodynamic alterations that have been associated with cardiovascular events. Changes in body fat with age may be related to aortic stiffening. The association between vascular stiffness and body fat was evaluated in 2488 older adults (mean age, 74 years; 52% female; 40% black) enrolled in the Study of Health, Aging, and Body Composition (Health ABC), a prospective study of changes in weight and body composition. Clinical sites were located in Pittsburgh, Pa, and Memphis, Tenn. Aortic pulse wave velocity was used as an indirect measure of aortic stiffness. A faster pulse wave velocity indicates a stiffer aorta. Body fat measures were evaluated with dual energy x-ray absorptiometry and computed tomography. Independent of age and blood pressure, pulse wave velocity was positively associated with weight, abdominal circumference, abdominal subcutaneous fat, abdominal visceral fat, thigh fat area, and total fat (
P
<0.001 for all). The strongest association was with abdominal visceral fat. Elevated pulse wave velocity was also positively associated with history of diabetes and higher levels of glucose, insulin, and hemoglobin A1c (
P
<0.001 for all). In multivariate analysis, independent positive associations with pulse wave velocity were found for age, systolic blood pressure, heart rate, abdominal visceral fat, smoking, hemoglobin A1c, and history of hypertension. The association between pulse wave velocity and abdominal visceral fat was consistent across tertiles of body weight. Among older adults, higher levels of visceral fat are associated with greater aortic stiffness as measured by pulse wave velocity.
Prevalence and Therapeutic Control of Hypertension in 30 000 Subjects in the Workplace
Authors: Lang Thierry , de Gaudemaris Régis , Chatellier Gilles , Hamici Lynda , Diène Eloi ,   for the Epidemiology Group of the Société Française d’Hypertension Artérielle and the IHPAF Working Physicians Group
Published: June 2012

—To assess blood pressure (BP) control in a French working population through the use of a careful assessment of BP based on 2 different visits in 1 month, 17 359 men and 12 267 women were evaluated from January 1997 to April 1998. The initial phase was a cross-sectional analysis of a cohort study designed to assess the incidence of arterial hypertension in a French working population. Information was collected by the work-site physician during the annual examination. BP was measured with a validated automatic device. Among subjects with BP ≥

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{140}{90}\) \end{document}

mm Hg, patients not treated with antihypertensive drugs were invited to have an additional BP measurement taken 1 month later. The prevalence of hypertension (BP ≥

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{140}{90}\) \end{document}

mm Hg) based on 2 visits was 16.2% in men and 9.4% in women. When the diagnosis of hypertension was based on 2 visits, its prevalence was 41% lower in men and 36% lower in women compared with that of a diagnosis based on a single visit. Accordingly, the awareness of hypertension was 49% higher in men and 40% higher in women. Overall, 12.5% of hypertensive men and 33.2% of hypertensive women taking antihypertensive medication had their BP levels lowered to <

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{140}{90}\) \end{document}

mm Hg by treatment. Although the percentage of hypertensive men and women under current treatment who were aware of their hypertension increased with age, BP control among treated subjects decreased with age. Ineffective BP control with treatment accounted for 33% of BP levels ≥

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{180}{110}\) \end{document}

mm Hg in men and 40% of those observed in women. In this large French working population, estimates of hypertension therapeutic control depend heavily on the number of BP measurements. Despite these methodological precautions, insufficient awareness of BP and insufficient BP control through treatment remain 2 major public health problems.
Role of the Medulla Oblongata in Hypertension
Authors: Colombari Eduardo , Sato Monica Akemi , Cravo Sergio Luis , Bergamaschi Cássia Toledo , Campos Ruy Ribeiro , Lopes Oswaldo Ubríaco
Published: June 2012

Abstract
—

— Brain pathways controlling arterial pressure are distributed throughout the neuraxis and are organized in topographically selective networks. In this brief review, we will focus on the medulla oblongata. The nucleus tractus solitarius (NTS) is the primary site of cardiorespiratory reflex integration. It is well accepted that lesions or other perturbations in the NTS can result in elevations of arterial pressure (AP), with many of the associated features so commonly found in humans. However, recent studies have shown 2 distinct subpopulations of neurons within the NTS that can influence AP in opposite ways. Commissural NTS neurons located on the midline may contribute to maintenance of hypertension in spontaneously hypertensive rats (SHR), because small lesions in this area result in a very significant reduction in AP. Also involved in this blood pressure regulation network are 2 distinct regions of the ventrolateral medulla: caudal (CVLM) and rostral (RVLM). Neurons in CVLM are thought to receive baroreceptor input and to relay rostrally to control the activity of the RVLM. Projections from CVLM to RVLM are inhibitory, and a lack of their activity may contribute to development of hypertension. The RVLM is critical to the tonic and reflexive regulation of AP. In different experimental models of hypertension, RVLM neurons receive significantly more excitatory inputs. This results in enhanced sympathetic neuronal activity, which is essential for the development and maintenance of the hypertension.
Effect of in vitro administration of captopril on vascular reactivity of rat aorta.
Authors: Kikta D C , Fregly M J
Published: June 2012

The effect of acute administration of captopril, an angiotensin converting enzyme inhibitor, on vascular responses of rings of rat aortic smooth muscle was tested in vitro. Dose-response curves for various vasoactive agents were obtained before and after exposure to captopril (2 x 10(-4) M) for 30 minutes. In the presence of captopril, contractile responses to angiotensin I (5 x 10(-10) to 5 x 10(-8) M) were attenuated significantly, probably as a result of decreased local conversion of angiotensin I to angiotensin II. Contractile responses to angiotensin II (10(-11) to 5 x 10(-9) M) were not affected by captopril. All responses to norepinephrine (10(-9) to 10(-4) M) and phenylephrine (10(-8) to 10(-4) M) were attenuated significantly from control in the presence of captopril. In the presence of the alpha-adrenergic antagonist, phentolamine, captopril did not affect either the contractile responses to KCl (30 to 100 mM) or the isoproterenol-induced (10(-8) to 10(-5) M) relaxation of KCl-depolarized tissue. These results suggest that captopril decreased vascular responsiveness to alpha-adrenergic agonists but not to beta-adrenergic agonists. Low concentrations of bradykinin (10(-10) to 10(-8) M) induced contraction in KCl-depolarized tissue while higher concentrations (10(-7) and 10(-6) M) induced relaxation. In the presence of captopril, relaxation occurred at all concentrations of bradykinin (10(-10) to 10(-6) M), probably as a result of decreased degradation of the bradykinin. These data suggest depression of alpha-adrenergic responsiveness in vascular smooth muscle as another potential antihypertensive action of captopril.
Renovascular hypertension in black patients.
Authors: Keith T A
Published: June 2012

In a 10-year period, 7200 of 19,000 black hypertensive adults in the University of Cincinnati Medical Center were referred to the Hypertension Service. In selected patients, intravenous urograms (1038) and renal arteriograms (238) were performed; 47 cases of renovascular hypertension (0.65% of the referred group and 0.25% of the entire sample) were identified. Atherosclerosis (32 patients) and fibromuscular dysplasia (11) were the most common causes of renal artery obstruction. Other lesions included traumatic thrombosis (2), Leriche syndrome (1), and postrenal transplant anastomotic thrombosis (1). Twenty-four patients were operated on (6 cured, 14 improved, 4 dead) and 23 treated medically (18 improved, 2 unimproved, 3 dead). Surgical mortality was 0. Follow-up exceeded 5 years in 25 patients. Extrarenal vascular lesions were found in 30 patients and accounted for six of seven deaths. Renal vein renin ratios greater than 1.5:1 (affected to unaffected side) predicted successful surgery in 14 patients, but eight of nine operated patients with ratios less than 1.5:1 also had favorable results. Factors in addition to renin assay were weighed before surgery was recommended. Since renovascular hypertension is rare in adult blacks, intensive investigation for this entity is justified only in patients with distinct suggestive findings. Treatment results in blacks are similar to those in white cohorts.
The role of calcium in the control of renin release.
Authors: Naftilan A J , Oparil S
Published: June 2012

The effects of removing external calcium and inhibiting entry of calcium into the cell by treatment with D-600 on renin release from renal cortical slices of male Sprague-Dawley rats were examined. Baseline renin release, angiotensin II (AII)-induced inhibition, and isoproterenol-induced stimulation of renin release were studied. Removal of external calcium by chelation with 5 mM EGTA inhibited basal renin release while treatment with 1 mM EGTA stimulated basal renin release slightly. Incubation of slices with zero calcium medium containing 1 mM EGTA had no effect on isoproterenol-induced stimulation of renin release. In contrast, similar treatment reduced the inhibitory effect of AII from 58.7% of baseline to 85.3% (p less than 0.001). Similarly, blockage of calcium entry into cells with D-600 had no effect on isoproterenol-induced stimulation of renin release but abolished AII-induced inhibition. Replacement of sodium in the bathing medium with choline had no effect on baseline renin release or on AII-induced inhibition of renin release, ruling out the possibility that D-600 altered renin release via an effect on sodium influx. Taken together, the data strongly suggest that AII-induced inhibition of renin release is partially dependent on the presence of external calcium but that isoproterenol-induced stimulation of renin release is not.
Hypotensive action of captopril in spontaneously hypertensive and normotensive rats. Interference with neurogenic vasoconstriction.
Authors: Clough D P , Hatton R , Keddie J R , Collis M G
Published: June 2012

The effects of captopril and angiotensin II on adrenergic neurotransmission have been studied in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). In a pithed rat preparation, vasoconstrictor responses evoked by spinal stimulation were greater in SHR than WKY (p less than 0.01). Captopril reduced responses to electrical stimulation and this reduction was greater in the SHR (p less than 0.001). Bilateral nephrectomy reduced the vasoconstrictor responses to nerve stimulation in both strains of rat and abolished the effects of captopril. In an isolated perfused mesenteric artery WKY (p less than 0.05). Angiotensin II potentiated responses from both strains of rat, however the amplitude of the potentiation was greater in preparations from the SHR than those from WKY (p less than 0.002). Captopril (30 mg/kg by mouth) reduced blood pressure in conscious SHR over a 5-day dosing period. In WKY rats, no hypertensive action of captopril was observed. However, in another normotensive strain, the Alderley Park Wistar rat (APW), captopril lowered blood pressure. Plasma renin activity was not significantly different among these three strains of rat. The APW have previously been shown to be very sensitive to the adrenergic potentiating actions of angiotensin II. Captopril thus lowers blood pressure in SHR and APW, and both these strains are sensitive to the adrenergic potentiating actions of angiotensin II. It does not lower blood pressure in WKY, which is relatively insensitive to these actions of the octapeptide. Therefore, the hypotensive action of captopril in the rat may be due to its interference with the adrenergic potentiating effect of angiotensin II.
Tail-cuff blood pressure measurement without external preheating in awake rats.
Authors: Buñag R D , Butterfield J
Published: June 2012

A new photoelectric sensor capable of detecting tail pulses even in unheated rats was tested for accuracy in indirect measurements of blood pressure. This sensor proved more sensitive than a Doppler ultrasonic flowmeter because it allowed detection not only of tail pulsations without preheating but also of peak oscillations usable for estimating mean arterial pressure. After blood pressures in anesthetized rats were elevated with norepinephrine or lowered with sodium nitroprusside, systolic pressures determined with the photoelectric sensor were almost identical with those recorded concurrently from femoral catheters (r = 0.939). Cuff pressure at peak oscillations in the tail correlated better with femoral mean pressure than with femoral diastolic pressure. However, similar comparisons in awake rats with chronically implanted carotid catheters showed that, although correlation between tail-cuff and carotid systolic pressures remained significant (r = 0.962), the correlation between peak tail oscillations and either mean or diastolic pressure was not. When systolic pressures were measured indirectly once a week for 7 weeks in unheated awake rats, normotensive rats could be easily distinguished from streptozotocin-diabetic and DOCA-salt hypertensive rats.
Sympathetic nerves protect the blood-brain barrier in stroke-prone spontaneously hypertensive rats.
Authors: Sadoshima S , Heistad D
Published: June 2012

Disruption of the blood-brain barrier may play a major role in the pathogenesis of hypertensive encephalopathy. In this study we determined whether sympathetic nerves to cerebral vessels protect the blood-brain barrier during chronic hypertension. We removed the cervical sympathetic ganglion on one side in 24 stroke-prone hypertensive rats when they were 1 month old. After signs of cerebral dysfunction developed at the mean age of 160 +/- 5 days (SE), we injected 125I-albumin and Evans blue dye intravenously to evaluate the permeability of the 125I-albumin was 3.53 +/- 0.83 (brain albumin x 100/blood albumin) in areas of the cerebrum stained with blue dye and 0.24 +/- 0.02 in unstained areas (p less than 0.05). We conclude that sympathetic nerves protect the blood-brain barrier against disruption during chronic hypertension and thereby may protect against hypertensive encephalopathy.
Structural and functional changes in cerebral arteries from spontaneously hypertensive rats.
Authors: Winquist R J , Bohr D F
Published: June 2012

Segments of basilar arteries from both spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied in vitro utilizing a microvessel apparatus. At similar levels of passive force, basilar arteries from SHR developed less force in response to depolarizing solution (130 mM K+) compared to basilar arteries from WKY. Arterial segments from the hypertensive animals required less stretch to achieve each level of passive force. Basilar arteries from SHR but not WKY typically displayed both phasic and tonic spontaneous activity which was inhibited in a reversible manner by washing the tissues in physiological salt solution without added Ca++ (EGTA, 1 mM). There was a significant shift to the left in the EC50 of serotonin and a greater maximal response to this agonist in basilar arteries from SHR compared to those from WKY (p less than 0.01). The EC50 to Ca++ (added to a depolarizing solution) was shifted to the right in the arteries from SHR compared to the normotensive controls (p less than 0.05). There was no difference between the arteries from the two groups of animals in the relaxation response produced by isoproterenol. However, contracted basilar arteries from SHR were less sensitive to the relaxant effects of elevated Ca++ than contracted basilar arteries from WKY (p less than 0.05). These results demonstrate the existence of both structural and functional difference between cerebral vessels of SHR and WKY. Our findings also demonstrate the complex nature of the changes in calcium dynamics in blood vessels from hypertensive animals.
Effects of atenolol and hydrochlorothiazide on blood pressure and plasma catecholamines in essential hypertension.
Authors: Myers M G , de Champlain J
Published: June 2012

The antihypertensive effects of atenolol and hydrochlorothiazide were compared with placebo in a randomized, double-blind crossover study, with the blood pressure responses related to sympathetic nervous system activity. Twelve patients with essential hypertension were given atenolol (100 mg), hydrochlorothiazide (50 mg), and placebo as single daily doses, each for 6 weeks. Mean supine, standing, and post-exercise blood pressures (mm Hg) on atenolol (155/94, 152/95, 177/93, respectively) and hydrochlorothiazide (154/99, 150/103, 172/96) were lower (p less than 0.01) than corresponding placebo values (172/109, 166/113, 204/111) at 6 weeks. The role of the sympathetic nervous system in the antihypertensive actions of atenolol and hydrochlorothiazide was examined. The supine plasma norepinephrine on placebo was used as an index of sympathetic activity to categorize each patient's "adrenergic status." The six "hyperadrenergic" patients with high resting norepinephrine values (mean, 302 pg/ml) exhibited a greater (p = 0.05) decrease in BP (-30/-20 mm Hg) on atenolol compared with the BP fall of -9/-11 mm Hg observed in the lower norepinephrine group (mean, 211 pg/ml). Resting plasma norepinephrine values did not predict the BP fall on hydrochlorothiazide. The "adrenergic status" of each patient as measured by the plasma norepinephrine concentration tended to be relatively constant regardless of therapy or the state of activity. In this study, atenolol was an effective antihypertensive agent comparable to hydrochlorothiazide in potency. Adrenergic status tended to predict the BP response to atenolol and was a relatively constant feature of the patients in all treatment phases.
Arterial wall uptake of renal renin and blood pressure control.
Authors: Loudon M , Bing R F , Thurston H , Swales J D
Published: June 2012

We have studied the contribution of circulating renin of renal origin to renin-like activity within the arterial wall and to blood pressure. Bolus injections of renin sufficient to elevate blood pressure by 44.7 mm Hg caused aortic renin to rise from 0.13 to 1.48 ng angiotensin I/100 mg/hr in nephrectomized rats. Elevation of aortic renin was still present at 6 hours, and this was associated with significant blood pressure elevation (p less than 0.05) which could be reversed by infusion of sarcosine, alanine, angiotensin II (saralasin). Prevention of the pressor effect by pretreatment with the converting enzyme inhibitor captopril did not reduce renin uptake. When kidneys were left in situ, although significant uptake of renin could be demonstrated 1 hour after injection, the increase at 3 hours was no longer significant (p greater than 0.05) and blood pressure returned to normal by 1 1/2 hours. This change in blood pressure may be related to the much more rapid clearance of circulating renin in the presence of normal kidneys or to other renal factors influencing the blood pressure response. The present studies demonstrate therefore that most of the renin-like activity within the aortic wall is derived from plasma renin and it seems probable that this component of the renin-angiotensin system plays an important role in blood pressure maintenance in the nephrectomized rats injected with renin. The relationship is less obvious in the presence of normal kidneys where additional influences may come into play.
Elevated blood viscosity in patients with borderline essential hypertension.
Authors: Letcher R L , Chien S , Pickering T G , Laragh J H
Published: June 2012

In patients with borderline hypertension, total peripheral resistance (TPR) is either elevated or abnormally related to cardiac output. Since blood viscosity is one determinant of TPR, we compared various components of blood viscosity in 25 patients with borderline hypertension and 25 normal subjects. Under all experimental blood flow conditions examined, blood viscosity directly correlated with systolic and diastolic blood pressure (p less than 0.05 or better) and was greater in the hypertensive than in normal subjects. Venous hematocrit and plasma viscosity were higher in the hypertensive patients. These latter rheologic abnormalities accounted for the increased blood viscosity at higher shear rates. At lower shear rates, increased red cell aggregation, primarily mediated by elevated fibrinogen concentration, accounted for the higher blood viscosity in the hypertensive subjects. We conclude that even relatively small elevations in arterial pressure are associated with increased viscous resistance of blood to flow, and that the increased blood viscosity is a consequence of increased hematocrit, plasma viscosity, and red cell aggregation.
Concurrent validity studies of blood pressure instrumentation. The Philadelphia Blood Pressure Project.
Authors: Barker W F , Hediger M L , Katz S H , Bowers E J
Published: June 2012

There is increasing evidence that blood pressure (BP) screening during adolescence may detect early evidence of hypertensive disease. Choice of instrumentation becomes important to maximize the accuracy and interpretive value of several serial readings. We therefore conducted two studies of adolescents, comparing auscultatory (Baumanometer and Random-zero), ultrasonic (Arteriosonde 1216), and infrasonic (Physiometrics SR-2) devices. These instruments were compared serially (Study 1) for older adolescents (n = 48). The Baumanometer, Arteriosonde 1216, and Physiometrics SR-2 were compared both serially and simultaneously (Study 2) for younger and older adolescents (n = 24). In both studies, the order of device presentation was completely counterbalanced. In Study 1, reliability estimates were high (r greater than 0.65), with the exception of the Arteriosonde 1216 diastolic readings, and the Physiometrics SR-2 yielded significantly lower mean diastolic BP readings than the other devices. Diastolic Phase V readings taken with the Random-zero were significantly higher when the Random-zero was presented at the end of the sequence of instrument presentation. This order of presentation effect is probably attributable to the need for overinflation when using the Random-zero device and may cause an overestimation of diastolic BP in the young. In Study 2, again the Arteriosonde 1216 did not perform reliably in recording diastolic BP. Further, the Physiometrics SR-2 device, although reliable, yielded diastolic readings significantly lower (p less than 0.001) than diastolic Phase IV readings taken both serially and simultaneously.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of endothelium in conversion of angiotensin I to angiotensin II in rabbit aorta.
Authors: Saye J A , Singer H A , Peach M J
Published: June 2012

Rabbit aortic rings with either an intact endothelium or a disrupted endothelium were used to generate dose response curves to angiotensin I (AI) in the presence (ED50 = 3 X 10(-7) M) and absence (ED50 = 1.7 X 10(-8) M) of 10 micrograms/ml teprotide, a converting-enzyme inhibitor. Treatment with teprotide did not alter responses to angiotensin II (AII). Comparable dose-dependent responses were obtained with AII regardless of endothelial integrity. Contraction velocities in response to angiotensin I (10(-7) M) and AII (10(-7) M) were also measured. Angiotensin II produced a significantly greater contraction velocity (p less than 0.001) than that produced by AI. The amount of conversion to AII by both intact rabbit aortic rings and rings following removal of the endothelium was determined using 125I-AI and 125I-AII. Waters C18 SEP-PAK columns were used to separate AI and AII. During the first 3 to 4 minutes after the addition of AI, contraction velocity measurements and conversion were greater in intact rings than rings without endothelium. Conversion of AI to AII in endothelial-disrupted rings was the same as in intact rings by 5 minutes after the addition of AI. Conversion of AI to AII was inhibited by 30 micrograms/ml teprotide at all times measured, and there was no evidence of an alternate route of metabolism. Angiotensin I contraction velocity measurements after 10 micrograms/ml teprotide also demonstrated impaired efficiency of conversion of AI to AII. Thus, it was established that a lack of endothelium attenuated the rate of conversion of AI to AII initially, and formation of AII with or without endothelium was blocked by teprotide.(ABSTRACT TRUNCATED AT 250 WORDS)
Dexamethasone hypertension in rats: role of prostaglandins and pressor sensitivity to norepinephrine.
Authors: Handa M , Kondo K , Suzuki H , Saruta T
Published: June 2012

Glucocorticoid hypertension was induced by oral administration of dexamethasone (DX) in male Wistar rats. The mechanism of hypertension was studied by observing the changes in plasma renin activity, urinary excretion of prostaglandin E2 (PGE2), and the pressor response to norepinephrine. Following administration of DX (0.1 mg/day), the blood pressure began to rise within 3 days and reached a plateau on the 5th day (from 108 +/- 2 to 162 +/- 7 mm Hg, mean +/- SE). On the other hand, urine volume and urinary excretion of sodium were increased. In spite of the marked natriuresis and diuresis, the administration of DX resulted in a marked decrease in the urinary excretion of PGE2. This decrease in PGE2 excretion appeared before the blood pressure rose and continued throughout the experiment. Plasma renin activity did not change. The pressor response to norepinephrine was enhanced on the 2nd day of DX treatment, at which time the blood pressure was not yet elevated, and it was further augumented on the 6th day. In the DX-treated rats, the pressor response to norepinephrine was not enhanced by administration of indomethacin, whereas the pressor response was significantly potentiated by indomethacin in control rats. These results suggest that DX-induced hypertension in rats is associated with inhibition of prostaglandin synthesis leading to increased sensitivity in the vascular response to norepinephrine.
Changes in leucocyte sodium transport in normotensive relatives of hypertensive subjects. Dissociation from blood pressure.
Authors: Milner M , Heagerty A M , Bing R F , Thurston H , Swales J D
Published: June 2012

It has been postulated that depressed membrane sodium transport is a necessary step in blood pressure elevation in essential hypertension. Accordingly, leucocyte sodium efflux-rate constants were estimated in 14 normotensive subjects who had one or more first-degree relatives with essential hypertension, and also in 14 matched control subjects with no such family history, before and after taking bendrofluazide for 7 days. Efflux rates in the controls did not change after the diuretic. However, in the relatives, mean total sodium efflux-rate constant was at first significantly depressed but later rose to normal with the diuretic. This was due almost entirely to an increase in glycoside-sensitive sodium pump activity. Blood pressure remained unchanged in both groups. Thus, assuming that perturbations in leucocytes reflect similar abnormalities in other cell lines, major changes in sodium transport in the normotensive individual without accompanying changes in blood pressure suggest that, while these changes may be a marker for later hypertension, they do not participate directly in blood pressure control.
Reduction of chronic psychosocial hypertension in mice by decaffeinated tea.
Authors: Henry J P , Stephens-Larson P
Published: June 2012

The effects of decaffeinated green tea on CBA mice have been contrasted with those of water during 3 to 5 months of exposure to various intensities of social stress. Intensity was modified by using different types of caging: Henry-Stephens complex population cages for maximum stress, open field population cages for intermediate levels, and siblings in standard mouse boxes for minimal stress. Two population densities were used: high, with 16 males and 16 females per population cage; and low, with approximately half this number. In three sets of experiments, 58 comparisons were made between body weight, blood pressure, pulse rate, scarring, blood urea nitrogen (BUN), adrenal and heart weights, plasma corticosterone, adult male mortality, and number of weanlings of those on decaffeinated green tea and matched groups on water. Twenty-five of the comparisons indicated less arousal with the decaffeinated green tea and in none was the water favored. Blood pressure fell from 150 to 133 mm Hg. These results support the proposal that the polyphenols (bioflavonoids) of tea may have a beneficial sedative action.
Sympathetic outflow to muscles during treatment of hypertension with metoprolol.
Authors: Wallin B G , Sundlöf G , Strömgren E , Aberg H
Published: June 2012

Microelectrode recordings of multiunit sympathetic vasoconstrictor activity were made in muscle branches of the peroneal nerve in patients with essential hypertension before and during long-term treatment with the cardioselective beta-adrenergic receptor antagonist metoprolol. Nerve activity was quantified by counting the number of sympathetic bursts in the mean voltage neurogram. Metoprolol treatment lowered blood pressure and heart rate in all subjects. During long-term treatment, nerve activity was reduced both when compared to the level of activity after the first dose of the drug (p less than 0.01) and when compared to the control level before treatment (p less than 0.05). It is suggested that the reduction of sympathetic vasoconstrictor outflow to muscles contributed to the blood pressure reduction.
What is the value of home blood pressure measurement in patients with mild hypertension?
Authors: Kleinert H D , Harshfield G A , Pickering T G , Devereux R B , Sullivan P A , Marion R M , Mallory W K , Laragh J H
Published: June 2012

To investigate the value of home blood pressure (BP) measurements, the BP was recorded daily by the patient at home and compared with recordings in the physician's office and with a 24-hour BP recording taken with a noninvasive ambulatory BP recorder in a group of 93 patients with mild untreated hypertension. Office BPs (mean 148/94 mm Hg) were higher than either home (138/89 mm Hg) or average 24-hour BPs (131/89 mm Hg). For systolic BP, home and office measurements gave similar correlations with 24-hour BP (0.67 and 0.55). For diastolic BP, however, home readings were lower and more accurate (0.76 vs 0.36). Thus, our findings indicate that home readings reflect the overall level of BP more reliably than office readings, and if due consideration is given to the fact that they are usually lower than office readings, they may be used as an alternative and cost-effective means of evaluating patients with mild hypertension.
Effects of high calcium intake on blood pressure and calcium metabolism in young SHR.
Authors: Stern N , Lee D B , Silis V , Beck F W , Deftos L , Manolagas S C , Sowers J R
Published: June 2012

Increased dietary calcium intake in the adult spontaneously hypertensive rat (SHR) has been reported to correct low serum ionized calcium concentration ([Ca++]) and to result in a significant amelioration of the prevailing hypertension. In the present study we examined several parameters of calcium metabolism in young (6-week-old) SHR and compared them with those observed in normotensive Wistar-Kyoto (WKY) rats fed equal amounts of a diet containing normal quantities of calcium (0.4%, wt/wt) for 4 weeks. A separate group of SHR was placed on an equal amount of a high calcium (2.8%, wt/wt) but otherwise identical diet. In SHR and WKY eating a normal calcium diet, serum total calcium concentration was not different, but [Ca++] was lower in SHR (1.58 +/- 0.06 vs 1.91 +/- 0.07 mmol/liter, p less than 0.01). Serum immunoreactive parathyroid hormone (PTH) was increased in some, but not all, SHR. No difference was noted between the two groups in the following parameters: calcium intake, serum 1,25 dihydroxycholecalciferol (1,25(OH)2D3), urinary calcium excretion, fractional stool calcium content ([stool calcium/calcium intake] X 100), and in vitro 45Ca uptake by everted gut sacs constructed from segments of duodenum, mid-jejunum, ileum, and proximal colon. A high calcium diet corrected the abnormal serum [Ca++] and PTH but did not alter the progression or severity of the hypertension in SHR. A lower net weight gain was observed in SHR on a high calcium diet when compared to SHR eating normal calcium diet (9.1 +/- 1.8 vs 27.0 +/- 2.0 g).(ABSTRACT TRUNCATED AT 250 WORDS)
Further evaluation of saline infusion for the diagnosis of primary aldosteronism.
Authors: Holland O B , Brown H , Kuhnert L , Fairchild C , Risk M , Gomez-Sanchez C E
Published: June 2012

Normal subjects, normal-renin hypertensive patients, and low-renin hypertensive patients were evaluated by intravenous saline infusion and with a fludrocortisone acetate (Florinef) protocol to clarify diagnostic criteria for primary aldosteronism that are recommended for the saline infusion protocol. The patients consumed a 200 mEq sodium, 70 mEq potassium diet for 6 days, and on the last 3 days received Florinef 0.5 mg orally twice daily. On Days 3 and 6, urinary aldosterone and tetrahydroaldosterone excretions were determined, and on Days 4 and 7 plasma aldosterone (PA) was determined at 0600 after overnight recumbency and at 0800 after 2 hours of walking. Although the level of normal PA suppression by saline infusion has been commonly defined as 10 ng/dl, a value of 5 ng/dl was originally recommended. In 20 normal subjects and 45 normal-renin hypertensive patients, we found that the PA was almost always suppressed below 5 ng/dl. In 18 of 75 low-renin patients including five with aldosterone-producing adenoma (APA), the PA was never suppressed below 10 ng/dl; thus, these 18 patients had classical primary aldosteronism by generally accepted criteria. The Florinef protocol was performed in eight of these 18 patients and was abnormal in all. An abnormal Florinef protocol was also found in seven of 15 patients studied with PA suppression after saline infusion to between 5 and 10 ng/dl, but in only one of 24 patients studied with PA suppression below 5 ng/dl. Additional studies in the subgroup with abnormal results from the Florinef protocol indicated that none of these patients had evidence of APA, so they had nontumorous primary aldosteronism (NTPA).(ABSTRACT TRUNCATED AT 250 WORDS)