bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Antihypertensive Agents on Local Arterial Distensibility and Compliance
Authors: Van Bortel Luc M. , Kool Mirian J. , Struijker Boudier Harry A.
Published: June 2012

Abstract
Distensibility and compliance are important vessel wall properties. Distensibility is related to elastic properties of the arterial wall, and compliance reflects the buffering function of the artery. Distensibility is a determinant of stress on the vessel wall. A decreased distensibility might increase the risk of arterial wall damage. Therefore, a preserved local distensibility might be important in protecting the arterial wall of each particular artery and especially of those arteries that are more susceptible to vascular disease. Local distensibility and compliance of various large arteries can be measured noninvasively with echo tracking techniques. Studies on local distensibility and compliance revealed that with the calcium antagonist verapamil and the angiotensin-converting enzyme inhibitor perindopril arterial compliance increased mainly because of an increase in distensibility, with only a minor effect on arterial diameter. In contrast, the nitrate compound isosorbide dinitrate increased compliance mainly by increasing arterial diameter, without an increase in distensibility. This indicates that an increase in arterial compliance does not automatically imply an increase in arterial distensibility. The effect of antihypertensive drugs may also depend on the vascular territory. The diuretic amiloride/hydrochlorothiazide increased brachial artery compliance but not common carotid artery compliance. During angiotensin-converting enzyme inhibition the effect on arterial compliance was smaller at the carotid than the femoral artery. However, the opposite held for the nitrate compound. These distinctive effects of antihypertensive drugs on arterial distensibility and compliance and on vascular territories may be relevant to pharmacological prevention and management of arterial disease.
Reduced Renal Extraction of Atrial Natriuretic Peptide in Primary Aldosteronism
Authors: Tunny Terry J. , Gordon Richard D. , Klemm Shelley A. , Stowasser Michael
Published: June 2012

Abstract
We investigated renal and peripheral forearm extraction of atrial natriuretic peptide in patients with primary aldosteronism to determine whether alterations in extraction may contribute to the elevated levels of circulating atrial natriuretic peptide observed in primary aldosteronism. We obtained simultaneous venous blood samples from the left renal vein and a peripheral vein and from the radial artery in 28 patients with primary aldosteronism and 10 patients with essential hypertension. Renal extraction of atrial natriuretic peptide was significantly (
P
<.001) reduced (40±2%) in primary aldosteronism compared with essential hypertensive patients (62±3%). Peripheral forearm extraction was also reduced (
P
<.01) in primary aldosteronism compared with essential hypertensive patients (24±3% versus 38±4%). These findings are consistent with widespread downregulation of atrial natriuretic peptide receptors in primary aldosteronism. Consistent with reports that marked reduction in glomerular filtration rate is required before the renal extraction of atrial natriuretic peptide is reduced, no significant relationship between renal extraction of atrial natriuretic peptide and plasma creatinine was seen in primary aldosteronism or essential hypertension. Although the major regulators of atrial natriuretic peptide secretion in primary aldosteronism are presumably alterations in arterial blood pressure and plasma volume, reduced renal and peripheral extraction of atrial natriuretic peptide in primary aldosteronism may also contribute significantly to the elevated circulating levels observed.
Acute Effects of Physiological Increments of Brain Natriuretic Peptide in Humans
Authors: La Villa Giorgio , Stefani Laura , Lazzeri Chiara , Zurli Claudia , Guerra Cristina Tosti , Barletta Giuseppe , Bandinelli Renzo , Strazzulla Gaetano , Franchi Franco
Published: June 2012

Abstract
To investigate the effects of physiological increases in plasma brain natriuretic peptide concentration in humans, we studied six healthy volunteers who received incremental infusions (0.25 pmol/kg per minute in the first hour and 0.50 pmol/kg per minute in the second) of synthetic human brain natriuretic peptide-32 in a placebo-controlled, crossover study. Peptide plasma levels were 1.69±0.39 pmol/L at baseline and rose 1.5- and 3-fold with the lower and higher doses, respectively. These values were within the normal range and also comparable to those reported in patients with mild essential hypertension. The urinary excretion rate of cGMP also increased during brain natriuretic peptide infusion, indicating stimulation of natriuretic peptide receptors. Peptide administration induced a significant 1.7-fold increase in urinary sodium excretion without affecting renal plasma flow (para-aminohippurate clearance), glomerular filtration rate (creatinine clearance), and urine flow rate. Fractional proximal sodium reabsorption (lithium clearance method) was unchanged, and fractional distal sodium reabsorption significantly decreased. Brain natriuretic peptide caused no changes in arterial pressure, heart rate, hematocrit, and serum proteins, but it exerted an inhibitory effect on the renin-aldosterone axis, as indicated by the significant 50% or more decrease of plasma renin activity and urinary excretion rate of aldosterone. These results suggest that brain natriuretic peptide may be involved in the overall regulation of body fluid and cardiovascular homeostasis in humans, mainly through its natriuretic and endocrine effects.
Apoptosis in Target Organs of Hypertension
Authors: Hamet Pavel , Richard Lucie , Dam Than-Vinh , Teiger Emmanuel , Orlov Sergei N. , Gaboury Louis , Gossard Francis , Tremblay Johanne
Published: June 2012

Abstract
Apoptosis or programmed cell death frequently parallels abnormalities in cell proliferation and differentiation. As hypertrophy/hyperplasia or remodeling occurs in organs affected by hypertension, we evaluated the degree of apoptosis in the heart, kidney, and brain in situ in genetically hypertensive mice and rats as well as in cultured vascular smooth muscle cells. Apoptosis was characterized by morphological features, DNA fragmentation, and laddering as well as by terminal deoxynucleotidyl transferase labeling of the 3′ OH ends of both extracted DNA and tissue sections. The present report provides the first evidence of increased apoptosis in whole organs of genetically hypertensive rat and mouse strains: in the heart of spontaneously hypertensive rats (SHR) and in the heart (ventricular cardiomyocytes), kidney (inner cortex and medulla), and brain (cortex, striatum, hippocampus, and thalamus) of spontaneously hypertensive mice, with a higher effect of apoptotic inducers in cultured aortic smooth muscle cells derived from SHR. Both types of known apoptotic processes, oligonucleosomal cleavage and large DNA fragmentation, were observed in vascular smooth muscle cells, but only the former appeared to be increased in SHR. This study underlines the importance of cell death dysregulation in hypertension, reveals a new route for investigation of the pathogenesis of hypertension, and suggests novel targets of therapeutic intervention.
Acute Exercise Attenuates Cardiac Autonomic Regulation in Hypertensive Rats
Authors: Chen Yifan , Chandler Margaret P. , DiCarlo Stephen E.
Published: June 2012

Abstract
Dynamic exercise may be used as a safe, therapeutic approach to reduce sympathetic nerve activity at rest and thus may be beneficial for individuals with hypertension. Therefore, we tested the hypothesis that a single bout of mild to moderate dynamic exercise would decrease cardiac sympathetic tonus at rest. We designed two experimental protocols to test this hypothesis in male spontaneously hypertensive rats. In protocol 1 (n=6) cardiac sympathetic tonus and parasympathetic tonus were determined before and after a single bout of dynamic exercise. We developed protocol 2 (n=5) to determine the component of the autonomic nervous system responsible for the postexercise reduction in heart rate. Rats were instrumented with catheters inserted into the descending aorta for measurements of arterial pressure, mean arterial pressure, and heart rate and into the jugular vein for infusion of drugs. A single bout of mild to moderate dynamic treadmill exercise (12 m/min, 10% grade for 42±1 minutes, representing approximately 74% to 79% of maximal heart rate) resulted in a postexercise reduction in mean arterial pressure (163±7 to 149±5 mm Hg;
P
<.05). Associated with the postexercise hypotension was a reduction in sympathetic and parasympathetic tonus (47±12% and 71±12%, respectively). The reduction in heart rate during the early recovery phase was due to a withdrawal of sympathetic tonus, because β
1
-adrenergic receptor blockade significantly enhanced the postexercise reduction in heart rate, and muscarinic-cholinergic receptor blockade did not affect the postexercise decrease in heart rate until 20 minutes after exercise. These results demonstrate that (1) sympathetic tonus and parasympathetic tonus are attenuated after a single bout of dynamic exercise and (2) the reduction in sympathetic tonus and parasympathetic tonus mediated cardiodeceleration during the early recovery period.
Endogenous Marinobufagenin-like Immunoreactive Factor and Na
+
,K
+
ATPase Inhibition During Voluntary Hypoventilation
Authors: Bagrov Alexei Y. , Fedorova Olga V. , Austin-Lane Joy L. , Dmitrieva Renata I. , Anderson David E.
Published: June 2012

Abstract
In previous studies investigators found that conditioned hypoventilatory breathing potentiated a sodium-sensitive form of hypertension in dogs that was not mediated by sympathetic nervous system arousal. Our study investigated effects of 30 minutes of voluntary hypoventilation, maintained by a respiratory gas monitor and feedback procedure, in 16 normotensive humans of both sexes on (1) plasma concentrations of endogenous digitalis-like factors (ouabain-like and marinobufagenin-like immunoreactivity), (2) activity of erythrocyte Na
+
,K
+
-ATPase, (3) inhibitory activity of plasma Na
+
,K
+
-ATPase, and (4) blood pressure. Increased end tidal P
co
2
(41±0.78 mm Hg versus 37.6±1.03 mm Hg) was associated with (1) an increase in plasma marinobufagenin-like immunoreactivity (1.23±0.47 versus 4.96±1.19 nmol/L), (2) an inhibition of Na
+
,K
+
-ATPase in red blood cells (3.68±0.22 versus 2.15±0.25 mmol P
i
· mL
−1
· h
−1
;
P
<.01), (3) increase in plasma Na
+
,K
+
-ATPase inhibitory activity (34.9±4.0% versus 48.8±2.1%,
P
<.02), and (4) increases in systolic (112.4±2.6 versus 107.6±1.8 mm Hg) and diastolic (73.5±2.1 versus 68.8±2.1 mm Hg) blood pressures. Plasma levels of ouabain-like immunoreactivity did not increase significantly. Incubation of erythrocytes obtained during hypoventilation with antidigoxin antibody restored the Na
+
,K
+
-ATPase activity (3.99±0.34 mmol P
i
· mL
−1
· h
−1
). Cessation of hypoventilation was associated with decreases in diastolic blood pressure (70.5±2.2 mm Hg) and restoration of Na
+
,K
+
-ATPase activity in erythrocytes (2.99±0.43 mmol P
i
· mL
−1
· h
−1
). On the basis of organic extraction and thin-layer chromatography followed by separation with the use of reverse-phase high-performance liquid chromatography, the material coeluting with marinobufagenin was separated from human urine. This material cross-reacted with anti-marinobufagenin antibody. These results demonstrate the presence of a bufadienolide-like Na
+
,K
+
-ATPase inhibitor in human plasma and support the view that breathing pattern may participate in blood pressure control via release of a rapidly acting circulating Na
+
,K
+
-ATPase inhibitor.
Insulin Resistance in Microalbuminuric Hypertension
Authors: Bianchi Stefano , Bigazzi Roberto , Galvan Alfredo Quiñones , Muscelli Elza , Baldari Giorgio , Pecori Neda , Ciociaro Demetrio , Ferrannini Ele , Natali Andrea
Published: June 2012

Abstract
Microalbuminuria in patients with essential hypertension is a marker of incipient glomerular dysfunction and clusters with lipid and hemodynamic abnormalities. Recent evidence has shown that hypertensive patients with microalbuminuria have a hyperinsulinemic response to oral glucose, suggesting the presence of insulin resistance. To directly test this possibility we studied insulin action in two accurately matched groups (n=10 each) of hypertensive patients with or without microalbuminuria (14±2 versus 52±7 mg · 24 h
−1
, mean of three 24-hour collections). In response to glucose ingestion microalbuminuric patients showed slight hyperglycemia (area under the curve, 928±43 versus 784±19 mmol ·L
−1
· 2 h
−1
,
P
<.02) and a marked hyperinsulinemia (26.8±3.3 versus 49.8±3.7 nmol · L
−1
· 2 h
−1
,
P
<.001). Basal arterial blood pressure, heart rate, and forearm blood flow were similar in the two groups and did not change significantly during a 2-hour euglycemic insulin clamp. Insulin-stimulated whole-body glucose uptake was 25% lower in microalbuminuric patients (33.5±2.5 versus 25.2±2.1 μmol · min
−1
· kg
−1
,
P
<.02). This difference was entirely due to a 40% reduction in glycogen synthesis (12.9±1.8 versus 21.3±3.2 μmol ·min
−1
·kg
−1
,
P
<.05) as glucose oxidation was similarly stimulated in the two groups. In contrast, there was no difference in the ability of insulin to suppress hepatic glucose production (by approximately 100% at the end of the clamp), to decrease fractional sodium and potassium excretions (by 35%), to lower circulating free fatty acids (by 80%), and to reduce plasma potassium concentrations (by 10%). Insulin sensitivity was inversely related to albumin excretion rate even after adjustment for body mass index (partial
r
=.51,
P
<.03). When both insulin sensitivity and the insulin area under the curve were entered into a multiple regression equation, the insulin area was more strongly related to albumin excretion and, together with 24-hour mean blood pressure, explained approximately 60% of its variability (
P
<.001). In conclusion, microalbuminuria in essential hypertension signals the presence of a selective impairment in peripheral insulin-mediated glucose uptake and an enhanced insulin secretory response to glucose. Insulin levels rather than insulin sensitivity appear to be related to urinary albumin excretion.
Target Organ Status and Serum Lipids in Patients With White Coat Hypertension
Authors: Pierdomenico Sante D. , Lapenna Domenico , Guglielmi Maria D. , Antidormi Teresa , Schiavone Cosima , Cuccurullo Franco , Mezzetti Andrea
Published: June 2012

Abstract
Target organ status and serum lipids were investigated in white coat hypertension in comparison with sustained hypertension and normotension. We selected three groups balanced for sex, age, body mass index, and smoking habit: 50 sustained hypertensives (clinical hypertension and 24-hour ambulatory blood pressure >135/85 mm Hg, a cutoff limit obtained from a normotensive population), 25 white coat hypertensives (clinical hypertension and 24-hour ambulatory blood pressure <135/85 mm Hg), and 25 normotensives. Subjects underwent echocardiographic examination to assess left ventricular mass index, carotid ultrasonography to evaluate intima-media thickness and atherosclerotic plaques, venous occlusion plethysmography to record minimum forearm vascular resistance, and determinations of serum lipid profile and 24-hour urinary albumin excretion. Compared with sustained hypertensives, the white coat hypertensives had significantly lower values of left ventricular mass index (125.9±20 versus 97.6±11.5 g/m
2
,
P
<.05), intima-media thickness (0.85±0.18 versus 0.71±0.15 mm,
P
<.05), minimum forearm vascular resistance (2.33±0.11 versus 2.04±0.08 resistance units,
P
<.05), urinary albumin excretion values (15.1±13.8 versus 4.45±1.48 mg per 24 hours,
P
<.0001), prevalence of left ventricular hypertrophy (38% versus 4%,
P
<.002), intima-media thickening (28% versus 4%,
P
<.015), and microalbuminuria (22% versus 0%,
P
<.015). No significant difference, however, was observed between the white coat hypertensives and the normotensives. Serum lipid profile was similar in the white coat hypertensives and in the normotensives. In conclusion, our data demonstrate that white coat hypertensives do not show target organ damage and do not present an unfavorable lipid profile, suggesting that they may be counseled on nonpharmacological therapy and that drug treatment could be withheld or delayed.
State of the Market
Authors: O’Brien Eoin , Atkins Neil , Staessen Jan
Published: June 2012

Abstract
The introduction of 24-hour ambulatory blood pressure measurement into clinical practice created a large market for ambulatory blood pressure measurement devices. Forty-three such devices from 31 manufacturers or suppliers are now available to satisfy a market demand that is likely to increase. The aim of this article is to identify the devices available and then to examine critically any validation studies assessing accuracy and performance. Of the 43 devices available 18 have been validated according to the protocols of the Association for the Advancement of Medical Instrumentation (AAMI) or the British Hypertension Society (BHS) in 25 reported studies. In 9 of these studies the protocol was not adhered to, and the results, which are therefore questionable, are noted but not considered further. Fourteen devices were evaluated according to the accuracy criteria of both protocols, and of these 9 fulfilled the requirements. From this review of 43 devices on the market it may be concluded that, at the time of writing, there is published evidence for only 9 devices meeting the generally accepted AAMI and BHS criteria for accuracy and performance; these are the A&D TM-2420 models 6 and 7 and TM-2421, CH-Druck, Nissei ABPM DS-240, Profilomat, QuietTrak, and SpaceLabs SL-90202 and SL-90207.
Intracellular Ca
2+
Release in Flow-Induced Contraction of Venous Smooth Muscle
Authors: Xie Hui , Laher Ismail , Bevan John A.
Published: June 2012

Abstract
We designed the present study to determine whether Ca
2+
release from intracellular stores contributes to flow-induced contraction. We carried out experiments on segments of rabbit facial vein under isometric conditions. Intraluminal flow by perfusion of physiological salt solution (10 to 80 μL/min) caused contraction in this vessel, which was significantly inhibited by (1) 30-minute pretreatment with 10 μmol/L ryanodine, the sarcoplasmic reticulum Ca
2+
channel opener, and (2) 30-minute pretreatment with concomitant application of 20 mmol/L caffeine and 1 μmol/L cyclopiazonic acid in Ca
2+
-free medium to deplete the sarcoplasmic reticulum. In comparison, contraction initiated by 300 nmol/L histamine was significantly attenuated by the same interventions. K
+
(25 mmol/L)–induced contraction was unaffected by ryanodine but was reduced after depletion of the sarcoplasmic reticulum. The phospholipase C inhibitor 2-nitro-4-carboxyphenyl-
N,N
-diphenylcarbamate (10 μmol/L) inhibited contractions induced by flow and histamine but not by K
+
. These findings indicate that Ca
2+
release from intracellular stores, presumably via the phosphatidylinositol pathway, contributes to flow- and histamine- but not raised K
+
–induced contractions in this vessel.
Noninvasive Ambulatory 24-Hour Blood Pressure in Patients With High Normal Blood Pressure and Exaggerated Systolic Pressure Response to Exercise
Authors: Lima Eliudem G. , Spritzer Nelson , Herkenhoff Fernando L. , Bermudes Ambrosina , Vasquez Elisardo C.
Published: June 2012

Abstract
Few studies have investigated the significance of abnormal increases in systolic pressure during exercise in patients with high normal blood pressure and its correlation with 24-hour ambulatory blood pressure monitoring and left ventricular structure. This study was performed in 30 sedentary subjects (42±4 years old) with high normal blood pressure. Fifteen subjects presenting <220 mm Hg systolic pressure during ergometric exercise were compared with 15 others with systolic pressure ≥220 mm Hg. Average 24-hour (systolic, 127±5 versus 142±4 mm Hg,
P
<.01; diastolic, 82±4 versus 92±3 mm Hg,
P
<.01), daytime (systolic, 130±6 versus 144±4 mm Hg,
P
<.01; diastolic, 84±4 versus 92±4 mm Hg,
P
<.01), and nighttime (systolic, 116±7 versus 132±6 mm Hg,
P
<.01; diastolic, 72±6 versus 85±6 mm Hg,
P
<.01) ambulatory blood pressure monitoring values were significantly higher in subjects with an exaggerated blood pressure response to exercise. No significant differences were observed in left ventricular morphology. These findings indicate that subjects presenting high normal blood pressure and exaggerated systolic pressure during exercise show significantly high ambulatory blood pressure monitoring values that are not associated with left ventricular hypertrophy.
Basal and Angiotensin II–Induced Cytosolic Free Calcium in Adult Rat Cardiomyocytes and Fibroblasts After Volume Overload
Authors: Fareh Jeannette , Touyz Rhian M. , Thibault Gaetan , Schiffrin Ernesto L.
Published: June 2012

Abstract
This study investigates basal and angiotensin II (Ang II)–induced [Ca
2+
]
i
concentrations in cells from hearts of rats that have undergone cardiac hypertrophy due to volume overload. [Ca
2+
]
i
measurements assessed by digital imaging using fura 2 methodology were performed on isolated ventricular cardiomyocytes and fibroblasts from adult rat hearts with a 4-week aortocaval shunt. Long-term aortocaval shunt induced a significant increase in atrial (72%) and ventricular (41%) weights and a large elevation in plasma atrial natriuretic peptide-(1-98) concentration (160%). For adult cardiomyocytes [Ca
2+
]
i
measurements are reported as diastolic (average of the lowest points) and systolic intracellular Ca
2+
values (average of the maximum points corresponding to the diastolic points) over a 30-second time interval. Basal diastolic [Ca
2+
]
i
(99±4.1 nmol/L for experimental cells versus 90±4.8 for control cells) was not altered, whereas basal systolic [Ca
2+
]
i
was significantly greater in ventricular cardiomyocytes from overload hearts (155±2.3 versus 129±4.4 nmol/L for control cells,
P
<.05). Ang II increased intracellular Ca
2+
spike frequency in a concentration-dependent manner in cardiomyocytes from control and overload myocardium. Basal and Ang II–induced intracellular Ca
2+
spike frequencies were not modified in cardiomyocytes from hypertrophied hearts. Basal [Ca
2+
]
i
in ventricular fibroblasts from overload myocardium was significantly increased (128±5.1 nmol/L for fibroblasts from hypertrophied hearts versus 104±3.5 for control cells,
P
<.05). Ang II–induced [Ca
2+
]
i
was lower in fibroblasts from overload myocardium (
P
<.05). In conclusion, alterations of intracellular calcium homeostasis in the two predominant cardiac cell types involved in myocardial growth and fibrosis, cardiomyocytes and fibroblasts, respectively, may contribute to the physiopathology of heart failure in adult rats. Ang II signaling through the intracellular calcium transduction pathway in a cell-specific manner may play an important role in cardiac hypertrophy.
Blood Pressure Influences the Occurrence of Complex Ventricular Arrhythmia in Hemodialysis Patients
Authors: De Lima José Jayme G. , Lopes Heno F. , Grupi César J. , Abensur Henry , Giorgi Maria Clementina P. , Krieger Eduardo M. , Pileggi Fulvio
Published: June 2012

Abstract
We investigated the relationship between blood pressure and the occurrence of complex ventricular arrhythmias (multiform, couplets, or runs) as assessed by 48-hour Holter monitoring in 74 stable long-term hemodialysis patients (44.5±12 years old; 54% men; 74% whites; dialysis duration, 51.3±36.1 months; systolic pressure, 146.6±19.3 mm Hg; diastolic pressure, 89.2±12.1 mm Hg; prevalence of arterial hypertension, 33.8%). Systolic and diastolic pressures represented the average of all predialysis determinations during the 3 months preceding the tests. Hemodialysis was performed midway through the Holter monitoring period. M-mode and bidimensional echocardiograms and myocardial perfusion tests were also obtained from all patients. Complex arrhythmias were observed in 37 individuals (50%). Univariate analysis showed that systolic pressure (
P
<.001), diastolic pressure (
P
<.05), age (
P
<.001), left ventricular posterior wall thickness (
P
<.01), left ventricular mass index (
P
<.05), and ischemic alterations on myocardial perfusion tests (
P
<.005) were significantly associated with complex arrhythmias. With the use of a multivariate model (stepwise logistic regression analysis) only systolic pressure (
P
<.01) and age (
P
<.05) were independently associated with complex arrhythmias. Sex; angina; dialysis duration; New York Heart Association functional class; use of digitalis; plasma levels of creatinine, sodium, potassium, calcium, and phosphate; hematocrit; left ventricular fractional shortening; left ventricular diastolic diameter; and ST segment deviation were not correlated with complex arrhythmias. The severity and frequency of complex arrhythmias were not influenced by hemodialysis. At follow-up (5 to 80 months) 5 patients had died of sudden death, 4 of whom were hypertensive and older than 45 years. We conclude that complex ventricular arrhythmias are highly prevalent in long-term hemodialysis patients, their occurrence is independently influenced by systolic pressure and age, and they are not aggravated by dialysis itself in this stable dialysis population. The data also suggest that Holter monitoring should be performed in elderly hypertensive dialysis patients.
Hypertension Prevalence, Awareness, Treatment, and Control in Egypt
Authors: Ibrahim M. Mohsen , Rizk Hussein , Appel Lawrence J. , Aroussy Wafaa El , Helmy Sherif , Sharaf Yasser , Ashour Zeinab , Kandil Hossam , Roccella Edward , Whelton Paul K.
Published: June 2012

Abstract
This report from the Egyptian National Hypertension Project presents national estimates of the prevalence of hypertension and the extent to which high blood pressure is being detected, treated with medications, and controlled in the Egyptian population. The results are based on findings from a national probability survey of adults ≥25 years of age conducted in six Egyptian governorates. With the use of a stratified multistage probability design, 6733 people (85% response rate) were examined. Hypertension was defined as systolic pressure ≥140 mm Hg, and/or diastolic pressure ≥90 mm Hg, and/or reported treatment with one or more antihypertensive medications. Overall, the estimated prevalence of hypertension in Egypt was 26.3%. Hypertension prevalence increased progressively with age, from 7.8% in 25- to 34-year-olds to 56.6% in those 75 years or older. Hypertension was slightly more common in women than in men (26.9% versus 25.7%, respectively). Overall, 37.5% of hypertensive individuals were aware that they had high blood pressure, 23.9% were being treated with antihypertensive medications, and 8.0% were under control (systolic pressure <140 mm Hg and diastolic pressure <90 mm Hg). Hypertension prevalence as well as awareness, treatment, and control rates varied by region, with Cairo having the highest prevalence (31.0%) and the Coastal Region having the highest control rate (15.9%). Rates of awareness, treatment, and control tended to be lowest in areas of lower socioeconomic status. Our results indicate that hypertension is highly prevalent in Egypt and that the rates of hypertension awareness, treatment, and control are relatively low. These findings argue for a nationwide effort to prevent and control high blood pressure in Egypt in order to avert an epidemic of cardiovascular disease.
Expression of Rat Kallikrein and Epithelial Polarity in Transfected Madin-Darby Canine Kidney Cells
Authors: Abe Masahiro , Nakamura Fumiaki , Tan Fulong , Deddish Peter A. , Colley Karen J. , Becker Robert P. , Skidgel Randal A. , Erdös Ervin G.
Published: June 2012

Abstract
Many properties of urinary kallikrein are well characterized, but the intracellular processing of prokallikrein and release by kidney cells have yet to be clarified. We report here on the synthesis of prokallikrein in Madin-Darby canine kidney (MDCK) cells transfected with rat submaxillary gland kallikrein cDNA and on its activation by MDCK cells and by an enriched liver Golgi membrane preparation. Transfected MDCK cells secreted only prokallikrein at both the apical and basolateral sides in about a 4:1 ratio, but cells transfected with kallikrein cDNA in reverse orientation or untreated cells released only traces of the enzyme. Prokallikrein, in culture medium or in homogenized MDCK cells, was fully activated by trypsin but activated only to 44% by thermolysin. Prokallikrein was synthesized and released into the medium at a high rate: the enzyme secreted by 5×10
6
cells in 24 hours cleaved 46 nmol/min
d
-Val-Leu-Arg-7-amino-4-methylcoumarin and liberated 63 ng/min bradykinin after activation. Immunocytology indicated the association of prokallikrein with the Golgi apparatus in the transfected cells. Antiserum to rat urinary kallikrein detected a single band in a Western blot of conditioned medium and also immunoprecipitated the enzyme. Aprotinin inhibited activated prokallikrein. Although MDCK cells released prokallikrein, their homogenates activated prokallikrein at both pH 5.5 and 7.5. Prokallikrein was also activated by a highly enriched liver Golgi membrane fraction and by an endoplasmic reticulum preparation, but the Golgi preparation was 38-fold more active. The activation was blocked significantly by inhibitors of serine proteases and less by cysteine protease inhibitors. Thus, transfected MDCK cells synthesize and release prokallikrein without activating it from the apical (80%) and the basolateral (20%) sides.
Effect of Hypothalamic-Hypophysary Inhibitory Factor on Mesangial Cell Activation
Authors: Rodríguez-Barbero Alicia , Martínez-Salgado Carlos , Rodríguez-López Ana M. , Ricote Mercedes , Sancho José , López-Novoa José M.
Published: June 2012

Abstract
We examined the effect of a sodium pump inhibitor isolated from bovine hypothalamus and pituitary tissues on contraction, proliferation, and calcium mobilization in primary cultures of rat mesangial cells. Hypothalamic-hypophysary inhibitory factor (HHIF) inhibited rubidium uptake in a concentration-dependent manner (0.2 U/mL: 56.8±6.3% inhibition). It also induced a concentration- and time-dependent decrease in planar cell surface area. Maximal contraction (25±5% reduction in cell size) was reached at 60 minutes with a concentration of 0.2 U/mL. This effect was inhibited by both verapamil and TMB-8 (10
−5
mol/L). HHIF was also observed to increase DNA synthesis (0.2 U/mL: 4361±168 versus 2129±162 cpm per well under control conditions) and cell proliferation (0.2 U/mL: 52 290±1931 versus 10 512±121 cells per well under control conditions). Both effects were also inhibited by verapamil and TMB-8. Moreover, HHIF induced the expression of immediate early genes c-
fos
and c-
jun
mRNA. HHIF-induced effects were accompanied by an increase in cytosolic free calcium (203±58 versus 101±2 nmol/L under control conditions), which was inhibited by verapamil and TMB-8. In summary, HHIF induces mesangial cell contraction and proliferation; these effects seem to be mediated by an increase in cytosolic free calcium levels.
Endothelin in the Kidney in Malignant Phase Hypertension
Authors: Whitworth Caroline E. , Veniant Murielle M. , Firth John D. , Cumming Allan D. , Mullins John J.
Published: June 2012

Abstract
A role for endothelin in malignant phase hypertension has been suggested on the basis of reported increases of circulating plasma immunoreactive endothelins in animal models. Recently, a hypertensive rat model that exhibits a genetically determined tendency for developing spontaneous onset malignant hypertension has been described. Expression of the three genes endothelin-1, endothelin-2, and endothelin-3 was quantified in the kidney by specific RNase protection assays in rats with established malignant hypertension, in rats with benign hypertension with and without a genetic susceptibility to malignant hypertension, and in normotensive Sprague-Dawley rats. Endothelin-1 mRNA levels were significantly elevated in the group with malignant hypertension compared with the other three groups. For determination of whether endothelin-1–mediated effects were crucial in the transition from benign to malignant phase hypertension, an oral nonspecific combined endothelin-A and endothelin-B receptor antagonist (bosentan) was given to hypertensive rats susceptible to malignant hypertension. No hypotensive effects were observed, and no significant difference in the incidence of malignant hypertension was observed between treated and control groups. In conclusion, although increased endothelin-1 mRNA expression was found in kidney tissue from rats developing malignant hypertension, blockade of endothelin-1–mediated effects did not prevent the transition from benign phase hypertension. Hence, increased renal endothelin-1 expression in this model of malignant hypertension does not appear to have a causative role and may simply reflect cellular damage and ischemia.
The Trough-to-Peak Ratio as an Instrument to Evaluate Antihypertensive Drugs
Authors: Staessen Jan A. , Bieniaszewski Leszek , Buntinx Frank , Celis Hilde , O’Brien Eoin T. , Van Hoof Roger , Fagard Robert
Published: June 2012

Abstract
The U.S. Food and Drug Administration designed the trough-to-peak ratio as an instrument for the evaluation of long-acting antihypertensive drugs, but the ratios are usually reported without accounting for interindividual variability. This study investigated how the trough-to-peak ratio would be affected by interindividual and intraindividual variability and by smoothing of the diurnal blood pressure profiles. The ambulatory blood pressure was recorded on placebo in 143 hypertensive patients (diastolic pressure on conventional measurement >95 mm Hg). After 2 months, the recordings were repeated on 10 mg (n=66) or 20 mg (n=77) lisinopril given once daily between 7 and 11
pm
. The baseline-adjusted trough-to-peak ratios were determined from diurnal blood pressure profiles with 1-hour precision. Lisinopril reduced (±SD) the 24-hour pressure by 16±17 mm Hg for systolic and 10±10 mm Hg for diastolic (
P<
.001). According to the usual approach, disregarding interindividual variability, the trough-to-peak ratio was 0.72 for systolic pressure and 0.67 for diastolic pressure. In the 143 patients the ratios were not normally distributed. They were the same on both lisinopril doses. When interindividual variability was accounted for, the median trough-to-peak ratio was 0.34 (P
5
to P
95
interval, −0.46 to 0.87) for systolic pressure and 0.26 (−0.44 to 0.84) for diastolic pressure. In 66 patients examined twice on 10 mg lisinopril at a median interval of 32 days, the trough-to-peak ratios were characterized by large intraindividual variability. The median trough-to-peak ratios increased (
P
<.001) when the individual blood pressure profiles were progressively smoothed by substituting 1-hour averages by 2-hour moving averages (systolic/diastolic pressure, 0.41/0.27), 2-hour averages (0.43/0.29), 3-hour moving averages (0.42/0.34), or 3-hour averages (0.47/0.36). In conclusion, the trough-to-peak ratio is idealized by not accounting for interindividual and intraindividual variabilities and by smoothing of the diurnal blood pressure profiles. If after review of its usefulness the trough-to-peak ratio is further instituted as an instrument in the evaluation of long-acting antihypertensive drugs, its determination and presentation must be regulated beyond the presently available recommendations.
Plasma Adrenomedullin Concentrations in Essential Hypertension
Authors: Kohno Masakazu , Hanehira Takao , Kano Hiroaki , Horio Takeshi , Yokokawa Koji , Ikeda Miwako , Minami Mieko , Yasunari Kenichi , Yoshikawa Junichi
Published: June 2012

Abstract
We designed the present study to assess any changes in plasma concentrations of the novel vasorelaxant peptide adrenomedullin in patients with essential hypertension. Plasma adrenomedullin concentrations were measured in 45 patients with untreated essential hypertension, 15 patients with borderline hypertension, and 30 normotensive control subjects. After 4 weeks of effective calcium channel blocker–based antihypertensive therapy, adrenomedullin concentrations were measured again. The concentrations were higher in hypertensive patients with increased serum creatinine levels or decreased glomerular filtration rates compared with borderline hypertensive patients and normotensive subjects, although values in normotensive and hypertensive individuals overlapped. Plasma adrenomedullin concentrations were positively correlated with serum creatinine levels and inversely correlated with glomerular filtration rates in the hypertensive patients, whereas adrenomedullin values were not correlated with blood pressure level, left ventricular mass index, or left ventricular ejection fraction. Despite blood pressure control with antihypertensive therapy, plasma adrenomedullin concentrations were not changed. Reversed-phase high-performance liquid chromatographic analysis showed that a major component of immunoreactive adrenomedullin in the plasma of normotensive subjects and hypertensive patients is human adrenomedullin-(1-52). These results indicate that plasma adrenomedullin concentrations are elevated in many hypertensive patients with renal dysfunction and its major component is human adrenomedullin-(1-52).
Glucocorticoid Modulates Vasodilator Response of Mesenteric Arterioles in Spontaneously Hypertensive Rats
Authors: Suzuki Hidekazu , Zweifach Benjamin W. , Schmid-Schönbein Geert W.
Published: June 2012

Abstract
We previously reported that the response of the arterioles in spontaneously hypertensive rats (SHR) to histamine is blunted compared with that in normotensive control rats (Wistar-Kyoto rats [WKY]). The present study was designed to analyze the extent to which this blunted arteriolar response may be attributed in SHR to the concurrent elevation of circulating glucocorticoids through the use of adrenalectomy with and without dexamethasone supplementation. Mesenteric arterioles were observed by intravital microscopy under general anesthesia, and their lumen diameters were measured after histamine superfusion. The concentration-response curve with histamine was compared with that of an endothelium-independent vasodilator, sodium nitroprusside. At the end of each experiment, papaverine was applied topically to determine the maximal diameter for each vessel, from which a measure of arteriolar tone could be computed. The arteriolar tone in sham-operated SHR is set at a higher steady-state level than in sham-operated WKY. The concentration required for a 50% dilator response (EC
50
) of histamine in adrenalectomized SHR was restored to the level of WKY. Adrenalectomy did not significantly affect the EC
50
of histamine in WKY. When adrenalectomized SHR received a supplement of dexamethasone, the arteriolar response was found to show the same refractory pattern to histamine as sham-operated SHR. In contrast, the EC
50
of sodium nitroprusside in sham-operated and adrenalectomized SHR was similar to that in sham-operated WKY. Our results indicate that the impaired dilator response to histamine in SHR is related to an enhanced adrenal glucocorticoid secretion.
Role of Vasopressin in Neurocardiogenic Responses to Hemorrhage in Conscious Rats
Authors: Imai Yutaka , Kim Choong-Yong , Hashimoto Junichiro , Minami Naoyoshi , Munakata Masanori , Abe Keishi
Published: June 2012

Abstract
Vasovagal reflexes, such as hypotension and bradycardia, are induced by rapid hemorrhage and mimic neurocardiogenic reflexes in mammals. We examined the role of vasopressin in the neurocardiogenic responses to mild, rapid hemorrhage (1 mL/100 g for 30 seconds) and severe hemorrhage (1 mL/100 g body wt for 30 seconds repeated three times at 11-minute intervals) in homozygous Brattleboro and Long-Evans rats. Mild, rapid hemorrhage induced severe bradycardia and hypotension only in Long-Evans rats. Exogenous vasopressin (1.85 pmol/kg per minute for 1 hour) restored both the bradycardic and hypotensive responses in Brattleboro rats. DDAVP, a vasopressin V
2
-receptor agonist (0.19 pmol/kg per minute for 24 hours), did not affect the cardiovascular responses to hemorrhage in Brattleboro rats, although it maintained urine production within normal limits. However, OPC-31260 (21.6 μmol/kg IV), a vasopressin V
2
-receptor antagonist, attenuated both the hypotensive and bradycardic responses to hemorrhage in Long-Evans rats. A vasopressin V
1
-receptor antagonist attenuated bradycardia and delayed the recovery of arterial pressure after hemorrhage but did not affect the hypotension that occurred immediately after hemorrhage in Long-Evans rats. Methylatropine also attenuated both the bradycardic and hypotensive responses induced by hemorrhage, but propranolol had no effect on the cardiovascular responses to hemorrhage in Long-Evans rats. The recovery of arterial pressure after repeated hemorrhage was less adequate in Brattleboro rats than in Long-Evans rats. Our results suggest that the neurocardiogenic responses to hemorrhage, especially hypotension, may be related to vasodilation induced by a V
2
-receptor–mediated mechanism and by the vagal reflex, both of which are substantiated by the existence of vasopressin. The coexistence of V
1
- and V
2
-receptor mechanisms may be necessary for the hypotensive response to hemorrhage. We found that a V
2
-receptor antagonist attenuated the hypotension mediated by the so-called neurocardiogenic reflex.
Chronic
l
-Arginine Administration Attenuates Cardiac Hypertrophy in Spontaneously Hypertensive Rats
Authors: Matsuoka Hidehiro , Nakata Masashi , Kohno Keisuke , Koga Yoshinori , Nomura Gakuji , Toshima Hironori , Imaizumi Tsutomu
Published: June 2012

Abstract
Nitric oxide inhibits proliferation and migration of vascular smooth muscle cells and contractility of cardiomyocytes in vitro. In spontaneously hypertensive rats (SHR), evidence suggests intrinsic abnormalities of the
l
-arginine–nitric oxide axis, such as low cGMP-dependent protein kinase in the heart and abnormal
l
-arginine metabolism. To investigate the in vivo effect of
l
-arginine on cardiac hypertrophy, 30 SHR and 30 Wistar-Kyoto rats (WKY) were randomly grouped to receive
l
-arginine (7.5 g/L in drinking water) or vehicle for 12 weeks.
l
-Arginine treatment did not affect body weight or arterial pressure in either strain. In vehicle-treated animals, the heart/body weight ratio was significantly higher in SHR than in WKY (
P
<.01).
l
-Arginine treatment decreased the heart/body weight ratio in SHR (
P
<.05) but did not affect it in WKY. Expression of skeletal α-actin mRNA, known to be expressed in the hypertrophied myocardium, was attenuated in
l
-arginine–treated SHR compared with vehicle-treated SHR. Cardiac cGMP content and nitrate/nitrite content were less in SHR than WKY.
l
-Arginine treatment increased these levels only in SHR, suggesting enhanced nitric oxide production. Thus, chronic
l
-arginine administration attenuated cardiac hypertrophy independently of blood pressure and increased myocardial content of cGMP and nitrate/nitrite. Our results suggest that abnormality of the cardiac
l
-arginine–nitric oxide axis may play an important role in the pathogenesis of cardiac hypertrophy in SHR.
Racial Difference in the Relationship of an Angiotensin I–Converting Enzyme Gene Polymorphism to Serum Angiotensin I– Converting Enzyme Activity
Authors: Bloem Laura J. , Manatunga Amita K. , Pratt J. Howard
Published: June 2012

Abstract
An insertion (I)/deletion (D) polymorphism of the angiotensin I–converting enzyme (ACE) gene that has been associated with certain cardiovascular disorders accounts for nearly half the variation in serum ACE level in white subjects. Whether a similar association of serum ACE with the I/D polymorphism occurs in other racial groups is not known. We studied the I/D polymorphism of ACE in relation to serum ACE activity in 141 white and 62 black healthy, unrelated children and adolescents (mean age, 14.7 years). The mean level of ACE activity in whites homozygous for the D allele was higher than in heterozygotes (
P
=.002) and in homozygotes for the I allele (
P
=.0001), consistent with an earlier study. In blacks, on the other hand, no significant difference in serum ACE activity between genotypes was observed. An additional finding was a significantly positive relationship between serum ACE activity and diastolic pressure (
P
=.009). In children and adolescents, serum ACE activity is related to the ACE gene I/D polymorphism in whites but not in blacks. The results indicate a potentially important ethnic variation in genetic regulation of serum ACE activity and the relationship of the I/D polymorphism to cardiovascular disease.
Blood Pressure and Its Regulation in Spontaneously Hypertensive Rats Bred on the Lowest Sodium Diet for Normal Growth
Authors: Takishita Shuichi , Fukiyama Koshiro , Eto Tanenao , Kawazoe Nobuyuki , Kimura Yorio , Tomita Yuji , Tsumagari Tatsumi , Onishi Kenichi
Published: June 2012

Abstract
To investigate the effects of dietary sodium restriction from conception to adulthood on blood pressure and its regulatory mechanisms, male offspring were derived from inbreeding in spontaneously hypertensive rats fed a diet containing sodium of 175 μmol/g food (control) or 22 μmol/g (low sodium), which is the least sodium content for normal growth. While urinary sodium excretion was markedly less, the low sodium diet did not inhibit body growth and failed to blunt the development of hypertension. Neither plasma catecholamine concentration nor depressor response to hexamethonium was different between the two groups at any age examined (8, 12, and 20 weeks). Plasma renin concentration was not elevated, whereas urinary excretion of aldosterone was increased at any age in the low sodium group compared with that in the control group. Other sets of rats were fed a diet containing sodium of 175 μmol/g plus mefruside (a diuretic) of 0.001% in the same manner as in the other two groups. Urinary sodium excretion per creatinine was higher than in the other groups. The diuretic treatment inhibited body growth and suppressed adult blood pressure. While the sympathetic function was not affected, both plasma renin concentration and urinary excretion of aldosterone were elevated. These results indicate that dietary sodium restriction with the least sodium for normal growth from conception cannot blunt either the sympathetic nervous function or the development of hypertension in spontaneously hypertensive rats. Aldosterone appears to play an important role in maintaining sodium homeostasis under the dietary sodium restriction.
Effects of Neonatal Growth on Adult Blood Pressures of Borderline Hypertensive Rats
Authors: Myers Michael M. , Handler-Matasar Sheryl R. , Shair Harry N.
Published: June 2012

Abstract
We conducted this study to test the hypothesis that there are long-term effects of litter-size manipulations during the preweaning period on growth and adult blood pressure of rats. Litter size of genetically homogeneous borderline hypertensive rats, which were produced by cross-mating male Wistar-Kyoto rats with female spontaneously hypertensive rats, was manipulated from 10 to 16 days of age. In addition, a subset of males and females was castrated within the first 30 hours of life. Body weights were measured at several preweaning and postweaning ages, and tail-cuff blood pressures were recorded at 90 days of age. Intact and castrated pups of both sexes that were reared in small (n=4) litters from 10 to 16 days of age gained nearly twice the weight of animals reared in large (n=9 to 12) litters during this period. Intact males from small litters had significantly higher adult blood pressures than those from large litters. These long-term effects remained even in groups matched for adult weight and length. Neonatal castration of males completely blocked the consequences of litter-size manipulation on adult blood pressure, suggesting either an organizational or activational role for androgens. Neither intact nor neonatally castrated females exhibited differences in adult blood pressure as a function of litter-size manipulation.