bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambulatory and Home Blood Pressure Normality in the Elderly
Authors: Sega Roberto , Cesana Giancarlo , Milesi Camilla , Grassi Guido , Zanchetti Alberto , Mancia Giuseppe
Published: June 2012

Abstract
To determine ambulatory blood pressure (BP) means and distributions in an elderly population, we studied a random sample of 800 subjects stratified by sex and representative of residents aged 65 to 74 years of the city of Monza. Participation was 50%. Measurements consisted of clinic BP (average of three measurements with mercury sphygmomanometry), home BP (average of morning and evening measurements with a semiautomatic device), and ambulatory BP (SpaceLabs 90207). Clinic BP was obtained before and after home and ambulatory BP measurements. In normotensive and untreated hypertensive subjects (n=248), clinic, home, and ambulatory BPs were significantly related (
P
<.001). The means of the clinic BPs obtained on consecutive days were very similar and markedly higher than 24-hour average BP (+25 mm Hg systolic and +10 mm Hg diastolic,
P
<.001). Nighttime BP was markedly less than daytime BP (−14 and −13 mm Hg,
P
<.001), whereas home BP values occurred approximately midway between clinic and 24-hour average BP values. Only minor differences existed between data in men and women, and the differences in clinic, home, and ambulatory BP values occurred in both normotensive and untreated hypertensive subjects. All BPs were similar in the untreated and treated hypertensive groups. Thus, as previously reported in subjects younger than 65 years, in the elderly fraction of the population, 24-hour average BP is much lower than clinic BP. The upper limit of normality for 24-hour average BP (calculated as the value corresponding to 140/90 mm Hg clinic BP) is about 120 mm Hg systolic and 76 mm Hg diastolic. At variance with data from younger subjects, home BP in the elderly is higher than 24-hour average BP. However, similar to data from younger subjects, clinic, home, and ambulatory BPs are higher in treated hypertensive than normotensive elderly subjects, indicating that in hypertensive elderly subjects, antihypertensive treatment does not commonly achieve full BP control both inside and outside the clinic environment.
Lisinopril Versus Hydrochlorothiazide in Obese Hypertensive Patients
Authors: Reisin Efrain , Weir Matthew R. , Falkner Bonita , Hutchinson Howard G. , Anzalone Deborah A. , Hypertension Michael L. Tuck for the Treatment in Obese Patients With
Published: June 2012

Abstract
Because obesity-associated hypertension has unique hemodynamic and hormonal profiles, certain classes of antihypertensive agents may be more effective than others as monotherapy. Thus, we compared the efficacy and safety of the angiotensin-converting enzyme inhibitor lisinopril and the diuretic hydrochlorothiazide in a 12-week, multicenter, double-blind trial in 232 obese patients with hypertension. Patients with an office diastolic pressure between 90 and 109 mm Hg were randomized to treatment with daily doses of lisinopril (10, 20, or 40 mg), hydrochlorothiazide (12.5, 25, or 50 mg), or placebo. Mean body mass indexes were similar for all patients. At week 12, lisinopril and hydrochlorothiazide effectively lowered office diastolic (−8.3 and −7.7 versus −3.3 mm Hg, respectively;
P
<.005) and systolic (−9.2 and −10.0 versus −4.6 mm Hg, respectively;
P
<.05) pressures compared with placebo. Ambulatory blood pressure monitoring confirmed that lisinopril and hydrochlorothiazide effectively lowered 24-hour blood pressure compared with placebo (
P
<.001). Significant dose-response differences were observed between treatments. Sixty percent of patients treated with lisinopril had an office diastolic pressure <90 mm Hg compared with 43% of patients treated with hydrochlorothiazide (
P
<.05). Responses to therapies differed with both race and age. Neither treatment significantly affected insulin or lipid profiles; however, plasma glucose increased significantly after 12 weeks of hydrochlorothiazide therapy compared with lisinopril (+0.31 versus −0.21 mmol/L;
P
<.001). Hydrochlorothiazide also decreased serum potassium levels by 0.4 mmol/L from baseline. In conclusion, lisinopril was as effective as hydrochlorothiazide in treating obese patients with hypertension. Treatment with angiotensin-converting enzyme inhibitors may show greater efficacy as monotherapy at lower doses compared with thiazide diuretics, may have a more rapid rate of response, and may offer advantages in patients at high risk of metabolic disorders.
\E Role for Endothelin-1 in Angiotensin II– Mediated Hypertension
Authors: Rajagopalan Sanjay , Laursen Jørn Bech , Borthayre Alain , Kurz Sabine , Keiser Joan , Haleen Steven , Giaid Adel , Harrison David G.
Published: June 2012

Abstract
Experiments in cultured vascular smooth muscle cells have shown that angiotensin II (Ang II) stimulates expression of endothelin-1. We sought to examine role of endothelin-1 in the effects of Ang II in vivo. Ang II infusion in rats (0.7 mg/kg per day for 5 days) was associated with marked increases in vascular smooth muscle endothelin-1 levels, as assessed by immunostaining. Administration of the selective endothelin type A (ET
A
) receptor antagonist PD 155080 (50 mg/kg per day) abrogated the hypertensive response to a 5-day infusion of Ang II (0.7 mg/kg per day), as did losartan (25 mg/kg per day). ET
A
receptor blockade during Ang II–mediated hypertension was associated with marked elevations of plasma endothelin-1 levels. Ang II–mediated hypertension was associated with heightened vascular responsiveness to a variety of vasoconstrictor agents except endothelin-1. Blockade of ET
A
receptor invariably corrected this vasoconstrictor hyperresponsiveness. We conclude that some of the vascular effects of Ang II thought to be unique to this hormone are likely mediated by endothelin-1.
Angiotensin II Type 1 (AT
1
) Receptor–Mediated Accumulation of Angiotensin II in Tissues and Its Intracellular Half-life In Vivo
Authors: van Kats Jorge P. , de Lannoy Larissa M. , Danser A. H. Jan , van Meegen Jan R. , Verdouw Pieter D. , Schalekamp Maarten A. D. H.
Published: June 2012

Abstract
Angiotensin II (Ang II) is internalized by various cell types via receptor-mediated endocytosis. Little is known about the kinetics of this process in the whole animal and about the half-life of intact Ang II after its internalization. We measured the levels of
125
I–Ang II and
125
I–Ang I that were reached in various tissues and blood plasma during infusions of these peptides into the left cardiac ventricle of pigs. Steady-state concentrations of
125
I–Ang II in skeletal muscle, heart, kidney, and adrenal were 8% to 41%, 64% to 150%, 340% to 550%, and 680% to 2100%, respectively, of the
125
I–Ang II concentration in arterial blood plasma (ranges of six experiments). The tissue concentrations of
125
I–Ang I were less than 5% of the arterial plasma concentrations.
125
I–Ang II accumulation seen in heart, kidney, and adrenal was almost completely blocked by a specific Ang II type 1 (AT
1
) receptor antagonist. Steady-state concentrations of
125
I–Ang II were reached within 30 to 60 minutes in the tissues and within 5 minutes in blood plasma. The in vivo half-life of intact
125
I–Ang II in heart, kidney, and adrenal was approximately 15 minutes, compared with 0.5 minute in the circulation. Thus, Ang II, but not Ang I, from the circulation is accumulated by some tissues, and this is mediated by AT
1
receptors. The time course of this process and the long half-life of the accumulated Ang II support the contention that this Ang II has been internalized after its binding to the AT
1
receptor, so that it is protected from rapid degradation by endothelial peptidases. The results of this study are in agreement with growing evidence of an important physiological role for internalized Ang II.
Xanthine Oxidase Inhibition With Oxypurinol Improves Endothelial Vasodilator Function in Hypercholesterolemic but Not in Hypertensive Patients
Authors: Cardillo Carmine , Kilcoyne Crescence M. , Cannon Richard O. , Quyyumi Arshed A. , Panza Julio A.
Published: June 2012

Abstract
Hypercholesterolemic and hypertensive patients have impaired endothelium-dependent vasorelaxation because of decreased nitric oxide activity, but the mechanism underlying this abnormality is unknown. This study sought to determine whether an increased breakdown of nitric oxide by xanthine oxidase–generated superoxide anions could participate in these forms of endothelial dysfunction. We studied vascular responses to intrabrachial infusion of acetylcholine (an endothelium-dependent vasodilator, 7.5 to 30 μg/min) and sodium nitroprusside (a direct smooth muscle dilator, 0.8 to 3.2 μg/min) by strain-gauge plethysmography before and during the combined administration of oxypurinol (300 μg/min), a xanthine oxidase inhibitor, in 20 hypercholesterolemic patients, 20 essential hypertensive patients, and 20 normal subjects. The vasodilator response to acetylcholine was blunted in hypercholesterolemic (highest flow, 8.2±8 mL·min
−1
·dL
−1
) and hypertensive (8.5±4 mL·min
−1
·dL
−1
) patients compared with control subjects (13.8±6.6 mL·min
−1
·dL
−1
) (both
P
<.001); however, no differences were observed in the response to sodium nitroprusside. Oxypurinol did not change the response to acetylcholine in control subjects (
P
=.26) and improved, but did not normalize, its vasodilator effect in hypercholesterolemic patients (
P
<.01). Oxypurinol did not affect the response to acetylcholine in hypertensive patients (
P
=.34) and did not modify the response to sodium nitroprusside in any group. These results suggest that xanthine oxidase–generated superoxide anions are partly responsible for the impaired endothelial vasodilator function of hypercholesterolemic patients. In contrast, this mechanism does not appear to play a significant role in essential hypertension.
Linkage of Essential Hypertension to the Angiotensinogen Locus in Mexican Americans
Authors: Atwood Larry D. , Kammerer Candace M. , Samollow Paul B. , Hixson James E. , Shade Robert E. , MacCluer Jean W.
Published: June 2012

Abstract
Essential hypertension has been linked to a highly polymorphic marker at the angiotensinogen locus, and association with a polymorphism in this locus has been found in some populations. We tested the hypothesis that these same polymorphic markers are linked to essential hypertension in Mexican Americans. The data comprised all the affected relative pairs in 46 extended families chosen at random from a low-income barrio in San Antonio. Specifically, we searched for linkage by testing for excessive marker alleles shared identical by descent (IBD) among hypertensive relative pairs. When women taking oral contraceptives or hormones were excluded, the affected relative pairs shared a significant excess of alleles IBD for the highly heterozygous GT repeat polymorphism (
P
=.038) and were marginally significant for the M235T variant (
P
=.079), which has a much lower heterozygosity (0.43 versus 0.85 for the GT repeat). We also assayed plasma levels of angiotensinogen and, using likelihood methods, found no significant association (
P
=.43) between plasma levels of angiotensinogen and M235T genotypes. These results support the linkage of essential hypertension to the angiotensinogen locus but do not indicate a specific role for the M235T variant.
Renal Angiotensin II Receptor Regulation in Two-Kidney, One Clip Hypertensive Rats
Authors: Amiri Farhad , Garcia Raul
Published: June 2012

Abstract
Local renal and plasma renin-angiotensin systems (RAS) both play an important role in blood pressure regulation during the development of two-kidney, one clip Goldblatt hypertension (2K1C) through their vasoactive component, angiotensin II (Ang II). Our goal was to characterize glomerular and preglomerular vascular Ang II receptors during the different stages of development of hypertension in 2K1C rats (2-, 4-, 8-, and 16-weeks postoperative) using Ang II antagonists [Sar
1
,Ile
8
]-Ang II, losartan, and PD 123319 and their regulation after angiotensin-converting enzyme (ACE) inhibition by captopril. Competitive binding studies showed that the only Ang II receptor detected on both glomeruli and preglomerular vessels of all groups (2-, 4-, 8-, and 16-week 2K1C rats, control rats, and captopril-treated rats) was the Ang II type 1 receptor (AT
1
). Vascular AT
1
receptor density (B
max
) was significantly lower in only the 16-week 2K1C group, whereas glomerular B
max
was significantly lower in 2K1C rats at 2-, 4-, and 8-weeks. Vascular and glomerular receptor densities were both significantly higher in captopril-treated rats than in nontreated rats. We therefore conclude that in 2K1C rats, Ang II receptors on preglomerular vessels and glomeruli are regulated differentially during the development of hypertension and after ACE inhibition. Our results suggest that glomerular Ang II receptors are regulated by systemic plasma Ang II levels, whereas vascular Ang II receptors are not. However, when renal and systemic RASs are both blocked, these receptors are upregulated but are no longer differentially regulated.
Losartan Versus Gene Therapy
Authors: Lu Di , Raizada Mohan K. , Iyer Shridhar , Reaves Phyllis , Yang Hong , Katovich Michael J.
Published: June 2012

Abstract
Interruption of the renin-angiotensin system by pharmacological manipulations attenuates high blood pressure (BP) in the spontaneously hypertensive rat (SHR). However, these agents, such as losartan, need to be administered daily to maintain effective BP control. Therefore, we have hypothesized that a genetic intervention in the expression of angiotensin type 1 receptor (AT
1
R) should attenuate development of hypertension on a long-term basis in SHR. A retroviral-mediated AT
1
R antisense cDNA gene delivery system (LNSV–AT
1
R-AS) was used to test this hypothesis and to compare its BP-lowering effects with those of losartan. Introduction of LNSV–AT
1
R-AS into 5-day-old Wistar-Kyoto rats and SHR resulted in a robust expression of AT
1
R antisense (AS) within 3 days and persisted for at least 30 days. This expression was associated with a selective attenuation of high BP in SHR by 25 to 30 mm Hg. Although basal lowering of BP was exclusive to SHR, the angiotensin II (Ang II) pressor response was significantly reduced in all LNSV–AT
1
R-AS–treated rats. The decreased response to Ang II was associated with a similar attenuation of Ang II–induced dipsogenic responses in both strains of rats. The BP-lowering effects of LNSV–AT
1
R-AS treatment and losartan treatment were similar and primarily observed in SHR. However, the antihypertensive effect lasted less than 24 hours in losartan-treated SHR compared with 90 days in LNSV–AT
1
R-AS–treated SHR. In addition, losartan was unable to further lower BP in LNSV–AT
1
R-AS–treated SHR. Collectively, these results suggest that both losartan and LNSV–AT
1
R-AS treatment produces an antihypertensive response selectively in SHR that is mediated by interruption of AT
1
R function. However, a single, acute genetic treatment with LNSV–AT
1
R-AS can result in long-term control of high BP at a similar level of effectiveness as losartan, without altering plasma Ang II levels.
Sympathetic and Cardiorenal Actions of Leptin
Authors: Haynes William G. , Sivitz William I. , Morgan Donald A. , Walsh Susan A. , Mark Allyn L.
Published: June 2012

Abstract
Body weight is tightly regulated physiologically. The recent discovery of the peptide hormone leptin has permitted more detailed evaluation of the mechanisms responsible for control of body fat. Leptin is almost exclusively produced by adipose tissue and acts in the CNS through a specific receptor and multiple neuropeptide pathways to decrease appetite and increase energy expenditure. Leptin thus functions as the afferent component of a negative feedback mechanism to control adipose tissue mass. Increasing evidence suggests that leptin may have wider actions influencing autonomic, cardiovascular, and endocrine function. Intravenous leptin increases norepinephrine turnover and sympathetic nerve activity to thermogenic brown adipose tissue. Studies from our laboratory suggest that leptin also increases sympathetic nerve activity to kidney, hindlimb, and adrenal gland. However, systemic administration of leptin does not acutely increase arterial pressure or heart rate in anesthetized animals. Thus, longer-term exposure to hyperleptinemia may be necessary for full expression of the expected pressor effect of renal sympathoexcitation. Alternatively, leptin may have additional cardiovascular actions to oppose sympathetically mediated vasoconstriction. Leptin in high doses increases renal sodium and water excretion, apparently through a direct tubular action. In addition, leptin appears to increase systemic insulin sensitivity, even in the absence of weight loss. Although we are at an early stage of understanding, we speculate that abnormalities in the actions of leptin may have implications for the sympathetic, cardiovascular, and renal changes associated with obesity.
Left Ventricular Filling Profiles in Young White-Coat Hypertensive Patients Without Hypertrophy
Authors: Chang Nen-Chung , Lai Zhi-Yang , Chan Paul , Wang Tze-Che
Published: June 2012

Abstract
This study was to assess left ventricular diastolic function in young white-coat hypertensive subjects <50 years of age without hypertrophy. Hypertensive patients (systolic or diastolic blood pressure ≥140 or ≥90 mm Hg on all three visits) were defined as white coat if their average 24-hour blood pressure was <127/81 mm Hg and at least 18/16 mm Hg lower than their average office values. We chose three groups balanced for sex, age, and body mass index: 50 sustained hypertensives, 25 white-coat hypertensives, and 25 normotensives. Office blood pressure was similar in white-coat and sustained hypertensives. Ambulatory blood pressure was comparable in white-coat hypertensives and normotensives. Compared with normotensives, white-coat hypertensives had more impaired diastolic function: increased ratio of late to early filling velocities, raised ratio of late to early time-velocity integral, prolonged deceleration time, and lengthened isovolumic relaxation time (
P
<.001,
P
<.001,
P=
.002, and
P
<.001, respectively). No difference was noticed between white-coat and sustained hypertensives. Compared with normotensives, white-coat hypertensives had higher values of plasma and urine norepinephrine (
P
<.001 and
P
<.001, respectively), plasma and urine aldosterone (
P
<.001 and
P=
.002, respectively), plasma renin activity (
P
=.04), total cholesterol (
P
=.001), and LDL cholesterol (
P
<.001). No difference was observed between white-coat and sustained hypertensives. Within white-coat hypertensives, 24-hour urinary aldosterone closely correlated with the ratio of late to early filling velocities (
P
=.008), and plasma and 24-hour urinary norepinephrine correlated well with total cholesterol (
P
=.037 and
P=
.006, respectively). No correlation was detected within the sustained hypertensives and normotensives. Heightened neurohumoral activity clearly supported the progression of diastolic dysfunction and metabolic abnormality in white-coat hypertensives.
Broadband Spectral Analysis of Blood Pressure and Heart Rate Variability in Very Elderly Subjects
Authors: Parati Gianfranco , Frattola Alessandra , Di Rienzo Marco , Castiglioni Paolo , Mancia Giuseppe
Published: June 2012

Abstract
Systolic blood pressure (SBP) variability is increased and R-R interval variability is reduced in the elderly. Little is known, however, about how SBP and R-R interval variabilities change in the very elderly. More important, however, it is not known which frequency components of SBP and R-R interval variability are affected significantly. We addressed this issue in subjects older than 70 years by broadband spectral analysis, which allows all variability components from the lowest to the highest frequency to be considered. In 20 very elderly normotensive subjects (mean±SD age, 78.1±6.8 years) and 28 normotensive adult subjects (36.1±7.1 years), noninvasive finger blood pressure and R-R intervals were recorded continuously for 30 minutes in the supine position and 15 minutes in the upright position. SBP and R-R interval power spectral densities were computed over the entire frequency region between 0.005 Hz (0.007 Hz in the upright position) and 0.5 Hz. Overall SBP variability (SD) was greater and overall R-R interval variability was less in very old subjects than in adult subjects. All spectral R-R interval powers were reduced significantly in very elderly individuals. The spectral SBP powers were greater in the very elderly group than in the adult group only in the very-low-frequency range (<0.04 Hz). This was true in the supine and the standing positions. With subjects in the standing position, the shape of the broadband spectra differed in the very old and adult subjects because in the former group the increase in SBP and R-R interval power around 0.1 Hz that was seen in the latter was blunted. Therefore, in very elderly subjects a reduction in overall R-R interval variability is accounted for by a reduction in all of its frequency components. The accompanying increase in overall BP variability, however, results from a nonhomogeneous behavior of its frequency components, which consists of an increase in the very low frequency and a concomitant reduction in the higher frequency powers. The mechanisms responsible for these changes may be complex, but at least they may in part reflect the baroreflex impairment and autonomic dysfunction that characterize aging.
Diastolic Pressure Underestimates Age-Related Hemodynamic Impairment
Authors: Galarza Carlos R. , Alfie José , Waisman Gabriel D. , Mayorga Luis M. , Cámera Luis A. , del Río Miguel , Vasvari Federico , Limansky Rodolfo , Farías Jorge , Tessler José , Cámera Mario I.
Published: June 2012

Abstract
It has been hypothesized that as large arteries become more rigid with age, the pattern of hypertension changes from diastolic to systolic. Thus, diastolic blood pressure (DBP) may lose its ability to reflect the increase in vascular resistance with age. To assess this, we studied the age-related changes in blood pressure pattern and its steady-state and pulsatile determinants. We performed an epidemiological analysis based on a national survey of 10 462 subjects from Argentina. A hemodynamic analysis (impedance cardiography) was then carried out in 636 consecutive hypertensive patients (age, 25 to 74 years). Whereas the rate of increment in the prevalence of mild to moderate hypertension (MMH) reached a plateau after the sixth decade, isolated and borderline systolic forms of hypertension began a steep and sustained rise. Among patients with MMH, DBP remained stable from the third to the seventh decade, whereas SBP maintained a sustained increase. Despite similar DBP, the systemic vascular resistance index increased 47% (
P
<.01) and the cardiac index decreased 27% (
P
<.01), whereas the ratio of stroke volume to pulse pressure, an index of arterial compliance, decreased 45% (
P
<.01). However, there were no significant differences between older patients with MMH and those with isolated systolic hypertension in the level of SBP, vascular resistance, stroke volume, and cardiac index. Compared with age-matched normotensive control subjects, the ratio of stroke volume to pulse pressure was much more reduced in isolated systolic hypertension (48%) than in MMH (30%). In summary, the present study, carried out in a large sample of hypertensive subjects with a wide age range, showed a simultaneous impairment in vascular resistance and arterial compliance associated with aging in different patterns of hypertension. The magnitude of these changes, with opposite effects on DBP but additive effects on SBP, suggests that a hemodynamic mechanism could determine the transition in the prevalence of diastolic hypertension toward a systolic pattern of hypertension with aging. Also, the results suggest that SBP, but not DBP, is a reliable indicator of the underlying hemodynamic abnormalities (high resistance and low arterial compliance) in the elderly.
Anatomic Heterogeneity of Vascular Aging
Authors: Barton Matthias , Cosentino Francesco , Brandes Ralf P. , Moreau Pierre , Shaw Sidney , Lüscher Thomas F.
Published: June 2012

Abstract
We investigated the effects of aging, a cardiovascular risk factor, on vascular function with regard to endothelial nitric oxide synthase (eNOS), superoxide dismutase (SOD), and endothelin (ET-1) in aorta and femoral artery of the rat. Concentration-response curves to acetylcholine, calcium ionophore A23187, norepinephrine, ET-1, big endothelin, sodium nitroprusside, and exogenous SOD were obtained. Expression of eNOS mRNA was analyzed by reverse-transcription polymerase chain reaction, SOD activity was assessed using a chemiluminescence-based cytochrome
c
assay, and ET-1 plasma concentrations were measured by radioimmunoassay. In aorta of old rats, relaxations to acetylcholine and calcium-ionophore A23187, basal NO release, and expression of eNOS mRNA in aortic endothelial cells were reduced (
P
<.05). In femoral arteries, relaxations to acetylcholine were preserved, whereas basal release of NO was attenuated (
P
<.05). Aging selectively increased contractions to norepinephrine and functional endothelin converting enzyme activity and attenuated contractions to ET-1 in aortas but not femoral arteries. Vascular SOD activity was higher in the femoral artery (
P
<.05) and unaffected by aging. Plasma ET-1 levels increased and plasma SOD activity decreased with age (
P
<.05). Aging was associated with an anatomic heterogeneity of endothelial dysfunction, functional endothelin converting enzyme activity, and vascular SOD activity. Vascular function was impaired in the aorta but not the femoral artery, which may be related to lower eNOS mRNA expression and SOD activity. These data suggest differential regulation of the vascular aging process that may contribute to the anatomic heterogeneity of atherosclerosis.
Dynamic Autoregulation and Renal Injury in Dahl Rats
Authors: Karlsen Finn M. , Andersen Claus B. , Leyssac Paul P. , Holstein-Rathlou Niels-Henrik
Published: June 2012

Abstract
The Dahl salt-sensitive (Dahl S) rat develops hypertension and renal injuries when challenged with a high salt diet and has been considered to be a model of chronic renal failure. Renal injuries appear very early in life compared with the spontaneously hypertensive rat (SHR). During the course of hypertension, a gradual impairment of autoregulatory control of renal blood flow might expose the glomerular circulation to periods of elevated pressure, resulting in renal injuries in Dahl S rats. Dynamic autoregulatory capacity was assessed in Dahl S and Dahl salt-resistant (Dahl R) rats, SHR, and Sprague-Dawley rats by inducing broad-band fluctuations in the arterial blood pressure and simultaneously measuring renal blood flow. Dynamic autoregulation was estimated by the transfer function using blood pressure as the input and renal blood flow as the output. Renal morphological injuries were evaluated in Dahl S rats and SHR and were scored semiquantitatively. Dynamic autoregulation was efficient and comparable in the low-frequency range (<0.015 Hz) in Dahl R rats, SHR, and Sprague-Dawley rats. The response in Dahl S rats depended strongly on the initiation time of the high salt diet. Autoregulation was preserved during a low salt diet and in rats exposed to a late-onset hypertension of short duration, only partly preserved if the late-onset hypertension was of a longer duration, and abolished in early-onset hypertension. All Dahl S rats on a high salt diet showed severe morphological changes in the kidney. In conclusion, autoregulatory capacity in the kidney of Dahl S rats is gradually impaired when rats are rendered hypertensive with a high salt diet. Renal morphological injuries develop before loss of dynamic autoregulation. Impaired autoregulation appears to be the result, not the cause, of the process that ultimately leads to renal failure in the Dahl S rat.
Antecedent Hypertension Confers Increased Risk for Adverse Outcomes After Initial Myocardial Infarction
Authors: Haider Agha W. , Chen Leway , Larson Martin G. , Evans Jane C. , Chen Ming Hui , Levy Daniel
Published: June 2012

Abstract
Several studies have examined the association of blood pressure (BP) after myocardial infarction (MI) with a risk for adverse outcome; however, few studies have investigated prognosis after MI as a function of BP before MI. Our goal was to examine the relation of antecedent hypertension to risk of adverse outcomes after initial MI. From 1967 to 1990, 404 subjects followed at the Framingham Heart Study developed an initial MI. These subjects were classified on the basis of preinfarction BP into normotensive (BP<140/90 mm Hg and not receiving antihypertensive treatment; n=118), stage I–untreated hypertension (BP 140 to 159/90 to 99 mm Hg; n=89), and stage II to IV or treated hypertension (BP ≥160/100 mm Hg or treated hypertension; n=197). Cox models were used to adjust for age, sex, smoking, glucose intolerance, total cholesterol, and prior cardiovascular disease. Antecedent hypertension was related to risk of adverse outcome after MI. Compared with normotensive individuals, stage II to IV hypertensives were at increased risk for reinfarction (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.20 to 4.04). A similar but nonsignificant association was seen in stage I hypertensives (HR, 1.91; 95% CI, 0.97 to 3.77). Stage II to IV hypertensives were at increased risk for all-cause mortality compared with normotensive persons (HR, 1.45; 95% CI, 1.07 to 1.98). Thus, even after MI, a history of antecedent hypertension remains predictive of adverse outcome. These findings are consistent with beneficial effects of BP control in primary and secondary prevention settings. Effective BP control may both reduce the risk for an initial MI and improve outcome in the event that an MI occurs.
Angiotensin Blockade Improves Cardiac and Renal Complications of Type II Diabetic Rats
Authors: Kim Shokei , Wanibuchi Hideki , Hamaguchi Akinori , Miura Katsuyuki , Yamanaka Shinya , Iwao Hiroshi
Published: June 2012

Abstract
Using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a new model of human non–insulin-dependent diabetes mellitus (NIDDM), we examined the role of local angiotensin II in cardiovascular and renal complications of NIDDM. OLETF rats were orally given cilazapril (an angiotensin-converting enzyme inhibitor, 1 or 10 mg/kg), E4177 (an angiotensin AT
1
receptor antagonist, 10 mg/kg), or vehicle for 26 or 40 weeks (from the age of 20 to 46 or 60 weeks). Cardiac mRNAs were measured by Northern blot analysis, and the thickening of the coronary arterial wall and the degree of perivascular fibrosis were determined by an image analyzer. Cilazapril or E4177 did not significantly affect body weight or plasma glucose and insulin levels of OLETF rats, indicating the minor effects on diabetes itself. However, both drugs significantly and similarly prevented coronary microvascular remodeling (the increase in wall thickening and perivascular fibrosis in coronary arterioles and small coronary arteries) in OLETF rats, and they were associated with the suppression of cardiac transforming growth factor-β1 expression. Both drugs suppressed not only the increase in left ventricular weight but also the downregulation of cardiac α-myosin heavy chain expression in OLETF rats. Glomerulosclerosis and glomerular hypertrophy in OLETF rats were improved by cilazapril and E4177 to a comparable extent. These results, taken together with the fact that OLETF rats show normal plasma renin levels, support that the AT
1
receptor is involved in the pathogenesis of cardiac and renal complications in NIDDM.
Malignant Vagotonia Due to Selective Baroreflex Failure
Authors: Jordan Jens , Shannon John R. , Black Bonnie K. , Costa Fernando , Ertl Andrew C. , Furlan Raffaello , Biaggioni Italo , Robertson David
Published: June 2012

Abstract
Baroreflex failure is characterized by dramatic fluctuations of sympathetic activity and paroxysms of hypertension and tachycardia. In contrast, unopposed parasympathetic activity has not been described in patients with baroreflex failure because of concurrent parasympathetic denervation of the heart. We describe the unusual case of a patient with baroreflex failure in a setting of preserved parasympathetic control of HR manifesting episodes of severe bradycardia and asystole. Thus, parasympathetic control of the HR may be intact in occasional patients with baroreflex failure. Patients with this selective baroreflex failure require a unique therapeutic strategy for the control of disease manifestations.
Insulin Resistance, Hyperinsulinemia, and Blood Pressure
Authors: Ferrannini Ele , Natali Andrea , Capaldo Brunella , Lehtovirta Mikko , Jacob Stefan , Yki-Järvinen for the European Group for the Study of Insuli Hannele
Published: June 2012

Abstract
In population surveys, blood pressure and plasma insulin concentration are related variables, but the association is confounded by age and obesity. Whether insulin resistance is independently associated with higher blood pressure in normal subjects is debated. We analyzed the database of the European Group for the Study of Insulin Resistance, made up of nondiabetic men and women from 20 centers, in whom insulin sensitivity was measured by the euglycemic insulin clamp. After excluding subjects aged ≥70 years, those with severe obesity (body mass index [BMI] >40 kg · m
−2
), and those with abnormal blood pressure values (≥140/90 mm Hg), 333 cases (ages 18 to 70 years; BMI, 18.4 to 39.8 kg · m
−2
) were available for analysis. In univariate analysis, both systolic and diastolic blood pressures were inversely related to insulin sensitivity, with
r
values of 0.18 (
P
<.005) and 0.34 (
P
<.0001), respectively. In a multivariate model simultaneously accounting for sex, age, BMI, and fasting insulin, systolic and diastolic blood pressures were still inversely related to insulin sensitivity (partial
r
, 0.15 and 0.19;
P
<.01 for both). In this model, age was positively related to blood pressure levels independently of insulin sensitivity, whereas BMI was not. The predicted impact on blood pressure of a decrease in insulin sensitivity of 10 μmol · min
−1
· kg
−1
was +1.4 mm Hg, similar to that associated with a 10-year difference in age. Although insulin levels and insulin action were reciprocally interrelated, diastolic blood pressure varied as a simultaneous function of both. In normotensive, nondiabetic Europeans, insulin sensitivity and age are significant, mutually independent correlates of blood pressure, whereas body mass is not. The relation of blood pressure to both insulin action and circulating insulin levels is compatible with distinct influences on blood pressure by insulin resistance and compensatory hyperinsulinemia.
Angiotensin II Has Depressor Effects in Pregnant and Nonpregnant Women
Authors: Broughton Pipkin Fiona , Baker Philip N.
Published: June 2012

Abstract
Studies in anesthetized animals suggest that angiotensin II evokes a depressor as well as a pressor effect, which becomes evident on cessation of infusion. We have studied 18 nonpregnant and 8, 23, and 22 women in the first, second, and third trimesters of pregnancy to determine whether such an effect is present in conscious women, whether it is dose dependent, and whether it is influenced by pregnancy. Angiotensin II was infused intravenously in doubling concentrations at 10-minute intervals until a pressor effect of ≈20 mm Hg was observed. The infusion was stopped, and blood pressure was monitored at 2-minute intervals for 30 minutes. There was a significant diastolic depressor effect after stopping angiotensin II in the nonpregnant women and those in the second and third trimesters of pregnancy. Individual women required differing doses of angiotensin II to evoke the standardized pressor response. It was thus possible to examine the depressor response in each group in relation to infused doses of angiotensin II. In nonpregnant women and in those in the second and third trimesters of pregnancy, the depressor response was dose dependent (
P
<.001). At any given dose, the depressor response deepened as pregnancy progressed (
P
<.001). Basal plasma prostacyclin concentrations rise in pregnancy, and angiotensin II can stimulate prostacyclin synthesis. This might mediate the depressor effect. In conclusion, the diminished pressor response to angiotensin II in normal pregnancy may be partly due to an increasing depressor effect of the hormone.
Relationship of Tachycardia With High Blood Pressure and Metabolic Abnormalities
Authors: Palatini Paolo , Casiglia Edoardo , Pauletto Paolo , Staessen Jan , Kaciroti Niko , Julius Stevo
Published: June 2012

Abstract
Faster resting heart rate has been shown to be associated with a higher risk of developing hypertension and a greater incidence of cardiovascular morbidity and mortality. The aim of this study was to investigate the distribution of heart rate and its relationship with blood pressure and other cardiovascular risk factors in three populations. One European general population (Belgian study), one North American general population (Tecumseh study), and one European hypertensive population (HARVEST trial) were studied. Within each population, mixture analysis was used to investigate whether a mixture of two normal distributions explained the variance in heart rate better than a single distribution. In the men of all populations, mixture analysis identified a larger subpopulation of subjects with normal heart rate and a smaller one with fast heart rate. The subgroups with tachycardia had higher blood pressure and lipid levels than those with normal heart rate. In the populations in which they were measured, fasting insulin and postload glucose were also higher in the men with faster heart rate. A subgroup with tachycardia could also be singled out among the women from Tecumseh, but no relation between heart rate and blood pressure could be found. These findings show that in Western societies, high heart rate pertains to a distinct subgroup of subjects, who are more frequently men and exhibit the characteristic features of the insulin resistance syndrome. Sympathetic overactivity is likely to be the mechanism underlying this clinical condition.
Captopril Modifies Gene Expression in Hypertrophied and Failing Hearts of Aged Spontaneously Hypertensive Rats
Authors: Brooks Wesley W. , Bing Oscar H. L. , Conrad Chester H. , O’Neill Lydia , Crow Michael T. , Lakatta Edward G. , Dostal David E. , Baker Kenneth M. , Boluyt Marvin O.
Published: June 2012

Abstract
The spontaneously hypertensive rat (SHR) exhibits a transition from stable compensated left ventricular (LV) hypertrophy to heart failure (HF) at a mean age of 21 months that is characterized by a decrease in α-myosin heavy chain (α-MHC) gene expression and increases in the expression of the atrial natriuretic factor (ANF), pro-α
1
(III) collagen, and transforming growth factor β
1
(TGF-β
1
) genes. We tested the hypotheses that angiotensin-converting enzyme inhibition (ACEI) in SHR would prevent and reverse HF-associated changes in gene expression when administered prior to and after the onset of HF, respectively. We also investigated the effect of ACEI on circulating and cardiac components of the renin-angiotensin system. ACEI (captopril 2 g/L in the drinking water) was initiated at 12, 18, and 21 months of age in SHR without HF and in SHR with HF. Results were compared with those of age-matched normortensive Wistar-Kyoto (WKY) rats, and to untreated SHR with and without evidence of HF. ACEI initiated prior to failure prevented the changes in α-MHC, ANF, pro-α
1
(III) collagen, and TGF-β
1
gene expression that are associated with the transition to HF. ACEI initiated after the onset of HF lowered levels of TGF-β
1
mRNA by 50% (
P
<.05) and elevated levels of α-MHC mRNA two- to threefold (
P
<.05). Circulating levels of renin and angiotensin I were elevated four- to sixfold by ACEI, but surprisingly, plasma levels of angiotensin II were not reduced. ACEI increased LV renin mRNA levels in WKY and SHR by two- to threefold but did not influence LV levels of angiotensinogen mRNA. The results suggest that the anti-HF benefits of ACEI in SHR may be mediated, at least in part, by effects on the expression of specific genes, including those encoding α-MHC, ANF, TGF-β
1
, pro-α
1
(III) collagen, and renin-angiotensin system components.
Perivascular Sensory Nerve Ca
2+
Receptor and Ca
2+
-Induced Relaxation of Isolated Arteries
Authors: Bukoski Richard D. , Bian Ka , Wang Yanlin , Mupanomunda Maria
Published: June 2012

Abstract
The present study tested two hypotheses: (1) that a receptor for extracellular Ca
2+
(Ca
2+
receptor [CaR]) is located in the perivascular sensory nerve system and (2) that activation of this receptor by physiological concentrations of extracellular Ca
2+
results in the release of vasodilator substance that mediates Ca
2+
-induced relaxation. Reverse transcription-polymerase chain reaction using primers derived from rat kidney CaR cDNA sequence showed that mRNA encoding a CaR is present in dorsal root ganglia but not the mesenteric resistance artery. Western blot analysis using monoclonal anti-CaR showed that a 140-kD protein that comigrates with the parathyroid CaR is present in both the dorsal root ganglia and intact mesenteric resistance artery. Immunocytochemical analysis of whole mount preparations of mesenteric resistance arteries showed that the anti-CaR–stained perivascular nerves restricted to the adventitial layer. Biophysical analysis of mesenteric resistance arteries showed that cumulatively raising Ca
2+
from 1 to 1.25 mol/L and above relaxes precontracted arteries with an ED
50
value of 2.47±0.17 mmol/L (n=12). The relaxation is endothelium independent and is unaffected by blockade of nitric oxide synthase but is completely antagonized by acute and subacute phenolic destruction of perivascular nerves. A bioassay showed further that superfusion of Ca
2+
across the adventitial surface of resistance arteries releases a diffusible vasodilator substance. Pharmacological analysis indicates that the relaxing substance is not a common sensory nerve peptide transmitter but is a phospholipase A
2
/cytochrome P450–derived hyperpolarizing factor that we have classified as nerve-derived hyperpolarizing factor. These data demonstrate that a CaR is expressed in the perivascular nerve network, show that raising Ca
2+
from 1 to 1.25 mol/L and above causes nerve-dependent relaxation of resistance arteries, and suggest that activation of the CaR induces the release of a diffusible hyperpolarizing vasodilator. We propose that this system could serve as a molecular link between whole-animal Ca
2+
balance and arterial tone.
Cellular Aspects of Vascular Remodeling in Hypertension Revealed by Confocal Microscopy
Authors: Arribas Silvia M. , Hillier Christopher , González Carmen , McGrory Simon , Dominiczak Anna F. , McGrath John C.
Published: June 2012

Abstract
Cellular aspects of remodeling in intact arteries have not been fully investigated, mainly due to the lack of an appropriate methodology that allows for simple measurements. The aim of this study was to develop a method based on laser scanning confocal microscopy (LSCM), compare it with previous methodology, and apply it to the study of remodeling in hypertension. The morphology of mesenteric resistance arteries from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) was determined with wire myography on one segment with a standardized diameter setting (0.9
d100
) and with perfusion myography on a second segment from the same artery at the calculated equivalent pressure. The second segments were stained with the nuclear dye Hoechst 33342 (live tissue) or propidium iodide (fixed tissue) and measured with LSCM and MetaMorph software. Compared with wire myography, perfusion myography showed similar differences from those previously reported. Compared with LSCM, perfusion myography showed a similar lumen but significantly smaller wall thickness in both live and fixed tissue, probably due to measurement underestimation. In the study with LSCM, arteries from SHRSP compared with those from WKY showed (1) reduced lumen, (2) altered cell density that was significantly increased in the adventitia, decreased in the media, and unchanged in the intima, (3) significantly increased medial volume, (4) significantly smaller endothelial cell nuclei, and (5) adventitial-like cells in the media. We conclude that (1) LSCM is a reliable and straightforward method to study morphology in intact vessels, (2) it provides new information on the cellular changes in remodeling, (3) adventitia might play an active role in the process of remodeling in hypertension, and (4) endothelium “remodels” in hypertension.
Lead-Induced Hypertension
Authors: Gonick Harvey C. , Ding Yaoxian , Bondy Steven C. , Ni Zhenmin , Vaziri Nosratola D.
Published: June 2012

Abstract
An elevation of mean blood pressure was found in rats treated with low lead (0.01% lead acetate) for 3 months, as contrasted to paired Sprague-Dawley control rats. In these rats, measurement of plasma and urine endothelins-1 and -3 revealed that plasma concentration and urinary excretion of endothelin-3 increased significantly after 3 months (plasma: lead group, 31.8±2.2, versus controls, 23.0+1.7 pg/mL,
P
<.001; urinary excretion: lead group, 46.6+11.7, versus controls, 35.6+6.7 pg/24 h,
P
<.05), whereas endothelin-1 was unaffected. Plasma and urinary nitric oxide (NO) and cyclic GMP concentrations were not significantly changed. However, assay of plasma and kidney cortex malondialdehyde by high-pressure liquid chromatography, as a measure of reactive oxygen species, was elevated in lead-treated rats compared with that in control rats (plasma: lead group, 4.74+1.27, versus controls, 2.14+.49 μmol/L,
P
<.001; kidney cortex: lead group, 28.75+3.46, versus controls, 16.38+2.37 nmol/g wet weight,
P
<.001). There was increased NO synthase activity in lead-treated rat brain cortex and cerebellum. In lead-treated rat kidney cortex, the endothelial constitutive NO synthase protein mass was unaffected, whereas the inducible NO synthase protein mass was increased. These data suggest a balance between increased NO synthesis and degradation (by reactive oxygen species) in lead-treated rats, which results in normal levels of NO. Thus, the hypertension may be related to an increase in the pressure substances, endothelin-3 and reactive oxygen species, rather than to an absolute decrease in nitric NO.