bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Sex on Arterial Hemodynamics and Blood Pressure
Authors: London Gerard M. , Guerin Alain P. , Pannier Bruno , Marchais Sylvain J. , Stimpel Michael
Published: June 2012

Abstract
Systolic pressure is lower in premenopausal women than in age-matched men, but underlying alterations are not well characterized. Aging and body size alter arterial function, influencing pressure wave propagation and amplification in peripheral and central arteries. To assess the possibility that systolic pressure differences in women are related to smaller body size, we studied arterial function in 119 men and 104 women. Premenopausal and postmenopausal women were compared with age-matched men. The following parameters were measured: ankle-arm pressure index (Doppler), aortic and arterial distensibility (pulse wave velocity), systolic pressure and the effect and time delay of arterial wave reflections in the common carotid artery (applanation tonometry), and diameters of the abdominal aorta and aortic bifurcation and their ratio (aortic tapering, echography). Premenopausal women had lower brachial (
P
<.05) and ankle (
P
<.01) systolic pressures than age-matched men, whereas the ankle-arm pressure index was higher in men (
P
<.01). In the overall population the ankle-arm index was positively correlated with body height (
P
<.001). Carotid systolic pressure was similar in women and men, with an increased effect and earlier return of wave reflections in women (
P
<.01). The effect of wave reflections was inversely correlated with body height (
P
<.001) and positively associated with aortic tapering (
P
<.001), which was increased in women (
P
<.01). In premenopausal women the distensibility of brachial and femoral arteries was higher than in age-matched men (
P
<.01), whereas aortic distensibility was not different. Postmenopausal women had arterial distensibility similar to that of age-matched men but still had an increased effect of wave reflections. This study shows that body height is positively correlated with systolic pressure amplification from central to peripheral arteries and inversely correlated with the effect of wave reflections in central arteries. Shorter body height in women results in less peripheral systolic pressure amplification, with lower peripheral but not central systolic pressure. Greater arterial distensibility in premenopausal women partially offsets the effects of shorter body height. After menopause, arterial distensibility is similar to that of age-matched men and does not compensate for smaller body size, resulting in a persisting increased effect of wave reflections in central arteries.
Renal Circulation and Blockade of the Renin-Angiotensin System
Authors: Hollenberg Norman K. , Fisher Naomi D. L.
Published: June 2012

Abstract
The mechanism by which angiotensin-converting enzyme (ACE) inhibition influences renal perfusion and function has assumed growing importance as alternatives for blocking the system have emerged. Neither renin inhibitors nor angiotensin II (Ang II) antagonists are likely to trigger responses similar to ACE inhibitor–induced involvement of kinins, prostaglandins, or nitric oxide. Several observations suggest species variation in the contribution of these pathways to the renal response to ACE inhibition. In humans, recent investigation suggests that virtually all of the renal response is due to a fall in Ang II formation. Perhaps most persuasive is the surprising observation that the renal hemodynamic response to renin inhibitors exceeds by more than 50% the response to ACE inhibition in healthy humans. To the extent that kinins or prostaglandins contribute to the renal response to ACE inhibition, one would anticipate a smaller response to renin inhibition. Possible explanations include an unanticipated additional action of renin inhibitors, better tissue penetration of these highly lipophilic agents, or more effective blockade of Ang II formation through an action at the rate-limiting step or non–ACE-dependent Ang II generation. Substantial evidence favors the latter two possibilities. Whatever the explanation, these observations raise the intriguing possibility that the undoubted therapeutic efficacy of ACE inhibition in renal injury, documented most rigorously for type I diabetes mellitus, might be exceeded with the newer classes of agent.
Effects of Hypertension and Dyslipidemia on the Decline in Renal Function
Authors: Mänttäri Matti , Tiula Eero , Alikoski Tiina , Manninen Vesa
Published: June 2012

Abstract
Experimental evidence suggests that in addition to hypertension, serum lipids might also accelerate the decline in renal function. We tested this hypothesis in 2702 dyslipidemic middle-aged men without renal disease participating in the Helsinki Heart Study, a coronary primary prevention trial. The decline in renal function was estimated from linear regression slopes based on reciprocals of 10 serum creatinine determinations over the study period. Renal function deteriorated 3% on average during the 5-year study, and hypertension accelerated this change. Subjects with an elevated ratio of low- to high-density lipoprotein cholesterol (>4.4) had a 20% faster decline than those with a ratio less than 3.2. Both the contribution of the lipoprotein ratio and the protective effect of high-density lipoprotein cholesterol alone remained significant in multiple regression analyses. In the study of joint effects the contribution of lipids was confined to subjects with simultaneous elevation of blood pressure and lipids. The results suggest that in addition to hypertension, blood lipids also modify the decline in renal function.
Regulation of Vascular Smooth Muscle Soluble Guanylate Cyclase Activity, mRNA, and Protein Levels by cAMP-Elevating Agents
Authors: Papapetropoulos Andreas , Marczin Nandor , Mora Gloria , Milici Antonio , Murad Ferid , Catravas John D.
Published: June 2012

Abstract
Although the biochemical properties of soluble guanylate cyclase (sGC) have been extensively studied, little is known about the regulation of gene expression of sGC subunits by second messengers. cAMP analogues and elevating agents have been previously shown to alter gene expression in vascular cells. The aim of the present study was to investigate the effects of cAMP-elevating agents on sodium nitroprusside–stimulated sGC activity and to correlate activity changes with mRNA and protein levels in cultured rat aortic smooth muscle cells. Pretreatment of cells with 50 to 1000 μmol/L isobutylmethylxanthine or 0.01 to 10 μmol/L forskolin led to a time- and concentration-dependent decrease in sodium nitroprusside–induced cGMP accumulation, first evident after 3 hours of pretreatment with forskolin and 6 hours of pretreatment with isobutylmethylxanthine. Incubation of cells with a protein kinase A–selective inhibitor (H89 or KT 5720) partially or fully prevented the downregulation in sodium nitroprusside–induced cGMP accumulation caused by cAMP-elevating agents. Quantification of reverse transcriptase–polymerase chain reaction products by high-performance liquid chromatography revealed that mRNA for both α
1
- and β
1
-subunits of sGC were decreased in cells pretreated with isobutylmethylxanthine and forskolin but not with dideoxyforskolin (inactive analogue). Moreover, protein levels for the sGC α
1
-subunit of cells pretreated with isobutylmethylxanthine and forskolin but not with dideoxyforskolin were decreased as indicated by Western blot analysis. These data indicate that cAMP-elevating agents decrease sGC activity, possibly by decreasing mRNA or protein levels or both.
Renin and Angiotensin II Receptor Gene Expression in Kidneys of Renal Hypertensive Rats
Authors: Haefliger Jacques-Antoine , Bergonzelli Gabriela , Waeber Gérard , Aubert Jean-François , Nussberger Jürg , Gavras Haralambos , Nicod Pascal , Waeber Bernard
Published: June 2012

Abstract
The aim of this investigation was to examine the interrelation between renal mRNA levels of renin and angiotensin II receptor type 1 (AT
1
) in a renin-dependent form of experimental hypertension. Rats were studied 4 weeks after unilateral renal artery clipping. Mean blood pressure and plasma renin activity were significantly higher in the hypertensive rats (n=10 206±8 mm Hg and 72.4±20.9 ng · mL
−1
· h
−1
, respectively) than in sham-operated controls (n=10, 136±3 mm Hg and 3.3±0.5 ng · mL
−1
· h
−1
, respectively). Northern blot analysis of polyA
+
RNA obtained from the kidneys of renal hypertensive rats showed increased levels of renin mRNA in the clipped kidney, whereas a decrease was observed in the unclipped kidney. Plasma renin activity was directly correlated with renin mRNA expression of the poststenotic kidney (
r
=.94,
P
<.01). AT
1
mRNA expression was lower in both kidneys of the hypertensive rats. This downregulation was specific for the AT
1A
subtype since the renal expression of the AT
1B
subtype remained normal in hypertensive rats. The downregulation of the renal AT
1A
receptor may be due to high circulating angiotensin II levels. This is supported by the significant inverse correlation (
r
=−.71,
P
<.01) between plasma renin activity and AT
1A
mRNA expression measured in the clipped kidney of the hypertensive rats.
L-NAME Hypertension Alters Endothelial and Smooth Muscle Function in Rat Aorta
Authors: Küng Christoph F. , Moreau Pierre , Takase Hiroyuki , Lüscher Thomas F.
Published: June 2012

Abstract
Nitric oxide is an important regulator of vascular function and blood pressure. Chronic administration of nitric oxide inhibitors provides a new model of hypertension with pronounced target organ damage. We investigated the effects of oral treatment with
N
ω
-nitro-
l
-arginine methyl ester (L-NAME) for 6 weeks on vascular reactivity of the aorta in Wistar-Kyoto rats. Certain rats received verapamil or trandolapril in addition to L-NAME. Systolic blood pressure increased in the L-NAME group (by ≈80 mm Hg systolic) but not in controls or rats treated with verapamil or trandolapril. Isometric tension changes of aortic rings were recorded. Endothelium-dependent relaxations to acetylcholine were reduced in the L-NAME group (58±6% versus 104±1% in placebo,
P
<.05) but were normalized by treatment with verapamil or trandolapril. In contrast, endothelium-independent relaxations to sodium nitroprusside were not significantly reduced in L-NAME hypertension but were slightly enhanced by trandolapril therapy (
P
<.05). Acute in vitro incubation of vessels with the thromboxane receptor antagonist SQ 30741 enhanced the relaxation to acetylcholine (
P
<.05) in the L-NAME group only. In quiescent rings, acetylcholine caused endothelium-dependent contractions in particular after in vitro incubation with L-NAME. These contractions tended to be enhanced in L-NAME hypertension (23±4% versus 14±3% in the placebo group;
P
=NS) and were significantly reduced after treatment with verapamil or trandolapril (
P
<.05). Contractions to norepinephrine and angiotensin I and II were unaffected by L-NAME hypertension, whereas those to endothelin-1 were reduced (
P
<.05). Thus, in the aorta, L-NAME–induced hypertension is associated with impaired endothelium-dependent relaxations, unmasking the effects of endothelium-derived vasoconstrictor prostanoids, and with a specific reduction of the contraction induced by endothelin-1. Chronic antihypertensive therapy with verapamil or trandolapril prevented this imbalance of endothelium-dependent relaxations and contractions and, in turn, normalized vascular function.
Oleic Acid Inhibits Endothelial Nitric Oxide Synthase by a Protein Kinase C–Independent Mechanism
Authors: Davda Rajesh K. , Stepniakowski Konrad T. , Lu Gang , Ullian Michael E. , Goodfriend Theodore L. , Egan Brent M.
Published: June 2012

Abstract
Many obese hypertensive individuals have a cluster of cardiovascular risk factors. This cluster includes plasma nonesterified fatty acid concentrations and turnover rates that are higher and more resistant to suppression by insulin than in lean and obese normotensive individuals. The higher fatty acids may contribute to cardiovascular risk in these patients by inhibiting endothelial cell nitric oxide synthase activity. To test this hypothesis, we quantified the effects of oleic (18:1[
cis
]) and other 18-carbon fatty acids on nitric oxide synthase activity in cultured bovine pulmonary artery endothelial cells by measuring the conversion of [
3
H]
l
-arginine to [
3
H]
l
-citrulline. Oleic acid (from 10 to 100 μmol/L) caused a concentration-dependent decrease in nitric oxide synthase activity at baseline and during ATP and ionomycin (Ca
2+
ionophore) stimulation. At 100 μmol/L, linoleic (18:2[
cis
]) and oleic acids caused similar reductions of nitric oxide synthase activity, whereas elaidic (18:1[
trans
]) and stearic (18:0) acids had no effect. Oleic acid also inhibited the endothelium-dependent vasodilator response to acetylcholine in rabbit femoral artery rings preconstricted with phenylephrine (
P
<.05) but had no effect on the response to nitroprusside. The pattern of 18-carbon fatty acid effects on nitric oxide synthase activity in endothelial cells is consistent with activation of protein kinase C. Although oleic acid increased protein kinase C activity in endothelial cells, neither depletion of protein kinase C by 24-hour pretreatment with phorbol 12-myristate 13-acetate nor its inhibition with staurosporine eliminated the inhibitory effect of oleic acid on nitric oxide synthase. The vascular ring studies further indicate that oleic acid reduces the response to acetylcholine by inhibiting nitric oxide synthase activity rather than reducing the activation of guanylate cyclase or the effects of cGMP. Thus, elevated oleic acid values in obese hypertensive individuals may contribute to impaired endothelium-dependent vasodilation by a protein kinase C–independent mechanism.
Attenuation of Genetic Hypertension After Short-term Vasopressin V1A Receptor Antagonism
Authors: Burrell Louise M. , Phillips Paddy A. , Risvanis John , Aldred Kathryn L. , Hutchins Ann-Marie , Johnston Colin I.
Published: June 2012

Abstract
Abnormalities of the vasopressin system are found in genetic hypertension. This study compares the delayed effects of a brief period of vasopressin V1A receptor blockade and angiotensin-converting enzyme inhibition in young female and male spontaneously hypertensive rats (SHR) on the development of hypertension in adult life. In a separate study, the role of vasopressin in the maintenance of blood pressure in adult SHR was assessed. Young SHR received either the nonpeptide vasopressin V1A receptor antagonist OPC-21268, the angiotensin-converting enzyme inhibitor ramipril, or vehicle from 6 to 10 weeks of age. During the treatment period, OPC-21268 and ramipril reduced systolic blood pressure compared with control SHR (
P
<.001). Blood pressure in male SHR 7 weeks after treatment withdrawal was 178±1 mm Hg in ramipril-treated, 184±1 mm Hg in OPC-21268–treated, and 200±2 mm Hg in control SHR (
P
<.001). Similar results were seen in female SHR, although both OPC-21268 and ramipril were less effective antihypertensive agents in female compared with male SHR. The sustained attenuation in blood pressure was not associated with significant cardiovascular structural changes (left ventricular–to–body weight ratio, renal weight–to–body weight ratio, mesenteric resistance artery media-to-lumen ratio). Results of vasopressin V1A receptor binding kinetics and plasma renin or aldosterone concentrations did not suggest a lasting effect of OPC-21268 on the vasopressin system or of ramipril on the renin-angiotensin system following treatment withdrawal. One week of OPC-21268 treatment in adult SHR had no effect on systolic blood pressure, indicating that vasopressin is not involved in the maintenance of blood pressure. In contrast, this study demonstrates the novel finding that brief vasopressin V1A blockade in young SHR attenuates the development of hypertension in adult SHR despite withdrawal of drug treatment. These results support a role for vasopressin in the development of hypertension.
Role of Nitric Oxide in Modulating the Vasoconstrictor Actions of Angiotensin II in Preglomerular and Postglomerular Vessels in Dogs
Authors: Schnackenberg Christine G. , Wilkins F. Clayton , Granger Joey P.
Published: June 2012

Abstract
The purpose of this study was to determine the role of nitric oxide in modulating the vasoconstrictor effect of angiotensin II (Ang II) on renal segmental resistances in the dog. To achieve this objective we examined the effect of intrarenal infusions of Ang II on preglomerular and postglomerular resistances in the presence and absence of intrarenal nitric oxide synthesis inhibition established by an intrarenal infusion of
N
G
-nitro-
l
-arginine-methyl ester at 5 μg/kg per minute in dogs. The whole-kidney stop-flow technique was used. Renal artery pressure was servo-controlled at 78±2 mm Hg throughout the study. Intrarenal infusion of Ang II alone at 0.5 and 2.0 ng/kg per minute increased renal vascular resistance (Δ0.064±0.011 and Δ0.171±0.030 mm Hg/mL per minute, respectively) and decreased renal blood flow (Δ21±4 and Δ45±9 mL/min). Associated with these changes, glomerular hydrostatic pressure and preglomerular resistance increased slightly (Δ1.1±0.9 and Δ1.6±1.8 mm Hg; Δ0.008±0.005 and Δ0.030±0.010 mm Hg/mL per minute, respectively), and postglomerular resistance increased markedly (Δ0.046±0.011 and Δ0.116±0.026 mm Hg/mL per minute). When dogs were pretreated with an intrarenal infusion of the nitric oxide synthesis blocker, Ang II at 0.5 and 2.0 ng/kg per minute increased renal vascular resistance (Δ0.271±0.058 and Δ1.088±0.242 mm Hg/mL per minute) and decreased renal blood flow (Δ28±5 and Δ62±9 mL/min). However, in sharp contrast to vehicle pretreatment, Ang II decreased glomerular hydrostatic pressure (Δ3.4±1.5 and Δ9.9±2.0 mm Hg), increased postglomerular resistance (Δ0.122±0.029 and Δ0.439±0.133 mm Hg/mL per minute), and increased preglomerular resistance (Δ0.109±0.031 and Δ0.487±0.099 mm Hg/mL per minute) in dogs pretreated with the nitric oxide synthesis inhibitor. In summary, these data indicate that during vehicle treatment Ang II infusion in the stop-flow kidney had a predominant effect on postglomerular resistance. However, when nitric oxide synthesis was blocked, Ang II had a profound effect on preglomerular resistance. These findings suggest that nitric oxide may play an important role in protecting mainly preglomerular vessels and to a lesser extent postglomerular vessels from Ang II–induced renal vasoconstriction in dogs.
Role of Periaqueductal Gray Matter in Hypertension in Spontaneously Hypertensive Rats
Authors: Schenberg Luiz Carlos , Lucas Brandão Carlos Augusto , Vasquez Elisardo Corral
Published: June 2012

Abstract
We performed experiments to study the effects of electrolytic lesions of periaqueductal gray matter on mean blood pressure, heart rate, and cardiac baroreflex in adult male spontaneously hypertensive rats. Cardiac baroreflex was assessed by the administration of randomly assigned doses of phenylephrine (0.3 to 5.0 μg/kg IV) or sodium nitroprusside (1.5 to 50 μg/kg IV) to unanesthetized rats. Bilateral lesions of the periaqueductal gray matter (0.5 mA/5 s) were then performed with rats under sodium pentobarbital anesthesia (35 mg/kg IP). Twenty hours after lesion, cardiac baroreflex was retested. Baroreflex data were analyzed by sigmoidal curve fitting. Lesion rats (n=12) showed a significant decrease in both the gain (Δ=−0.89±0.38 beats per minute [bpm]/mm Hg,
P
<.05) and curve midpoint (Δ=−15±6 mm Hg,
P
<.05) of the cardiac baroreflex. Moreover, despite a moderate increase in heart rate (Δ=34±10 bpm,
P
<.01), resting mean blood pressure was significantly decreased 24 hours after the lesions (Δ=−19±5 mm Hg,
P
<.01). No significant changes in cardiac baroreflex were observed in sham-lesion rats (n=12). Histological examination showed circumscribed bilateral damage of dorsolateral periaqueductal gray matter. Dorsolateral periaqueductal gray matter is an area of the brain putatively related to fear and anxiety. It also projects onto premotor sympathetic neurons in the medulla. Although electrolytic lesions damage neurons as well as fibers of passage, these data suggest that dorsolateral periaqueductal gray matter has a far greater influence on resting cardiovascular control in spontaneously hypertensive rats than was previously suspected.
Relationship Between Systemic Hemodynamics and Ambulatory Blood Pressure Level Are Sex Dependent
Authors: Alfie José , Waisman Gabriel D. , Galarza Carlos R. , Magi Marissa I. , Vasvari Federico , Mayorga L. Marcelo , Cámera Mario I.
Published: June 2012

Abstract
Sex-related differences in systemic hemodynamics were analyzed by means of cardiac index and systemic vascular resistance according to the level of daytime ambulatory blood pressure. In addition, we assessed the relations between ambulatory blood pressure measurements and systemic hemodynamics in male and female patients. We prospectively included 52 women and 53 men referred to our unit for evaluation of arterial hypertension. Women and men were grouped according to the level of daytime mean arterial pressure: <110 or ≥110 mm Hg. Patients underwent noninvasive evaluation of resting hemodynamics (impedance cardiography) and 24-hour ambulatory blood pressure monitoring. Compared with women men with lower daytime blood pressure had a 12% higher systemic vascular resistance index (
P
=NS) and a 14% lower cardiac index (
P
<.02), whereas men with higher daytime blood pressure had a 25% higher vascular resistance (
P
<.003) and a 21% lower cardiac index (
P
<.0004). Furthermore, in men systemic vascular resistance correlated positively with both daytime and nighttime systolic and diastolic blood pressures, whereas cardiac index correlated negatively only with daytime diastolic blood pressure. In contrast, women did not exhibit any significant correlation between hemodynamic parameters and ambulatory blood pressure measurements. In conclusion, sex-related differences in systemic hemodynamics were more pronounced in the group with higher daytime hypertension. The relations between systemic hemodynamics and ambulatory blood pressure level depended on the sex of the patient. In men a progressive circulatory impairment underlies the increasing level of ambulatory blood pressure, but this was not observed in women.
Human Atrial Natriuretic Peptide Gene Delivery Reduces Blood Pressure in Hypertensive Rats
Authors: Lin Kuei-Fu , Chao Julie , Chao Lee
Published: June 2012

Abstract
Chronic infusion of atrial natriuretic peptide (ANP) has been shown to cause natriuresis, diuresis, and hypotension in rats and humans. We explored the effect of a continuous supply of ANP by somatic ANP delivery on genetically hypertensive rats. A DNA construct containing the human ANP gene fused to the Rous sarcoma virus 3′-long terminal repeat (RSV-LTR) was injected intravenously into spontaneously hypertensive rats (SHR) through the tail vein. Expression of human ANP in SHR was identified in the heart, lung, and kidney by radioimmunoassay and reverse transcription–polymerase chain reaction followed by Southern blot analysis. A single injection of naked ANP plasmid DNA (12.3 kb) caused a significant reduction of systemic blood pressure in young SHR (4 weeks old), and the effect continued for 7 weeks. The differences were significant at 1 to 2 weeks (n=6,
P
<.05) and 3 to 6 weeks after injection (n=6,
P
<.01) A maximal blood pressure reduction of 21 mm Hg in young SHR was observed 5 weeks after injection with ANP DNA (159.4±3.02 mm Hg, mean±SEM, n=6) compared with SHR injected with vector DNA alone (180.2±3.02 mm Hg, mean±SEM; n=6;
P
<.01). Somatic gene delivery of human ANP DNA had no effect on the blood pressure of adult SHR (12 weeks old). After ANP gene delivery, there were significant increases in urinary volume and urinary potassium output (n=6,
P
<.05) but not in body weight, heart rate, water intake, urinary sodium output, urinary creatinine, and urinary protein. Antibodies to human ANP or plasmid ANP DNA were not detected in rat sera. These results indicate that somatic delivery of the human ANP gene induces a sustained reduction of systemic blood pressure in young hypertensive rats and raise the feasibility of using ANP gene therapy for the treatment of human hypertension.
Role of Superoxide in the Depressed Nitric Oxide Production by the Endothelium of Genetically Hypertensive Rats
Authors: Grunfeld Saul , Hamilton Carlene A. , Mesaros Stephan , McClain Steven W. , Dominiczak Anna F. , Bohr David F. , Malinski Tadeusz
Published: June 2012

Abstract
We undertook these studies to determine whether a deficient nitric oxide production in genetically hypertensive rats could result from its being scavenged by an excess production of superoxide. In one study we used a porphyrinic microsensor to measure nitric oxide concentrations released by cultured endothelial cells from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). SHRSP cells released only about one third the concentration of nitric oxide as did WKY cells. Treatment of cells with superoxide dismutase increased nitric oxide release, demonstrating that normally nitric oxide is scavenged by endogenous superoxide. The increase in nitric oxide release in response to superoxide dismutase treatment was more than twice as great from SHRSP as from WKY cells, demonstrating the greater amount of superoxide in the hypertensive rats. A direct measure of superoxide with the use of lucigenin demonstrated the presence of 68.1±7.1 and 27.4±3.5 nmol/L of this anion in SHRSP and WKY endothelial cells, respectively. The presence of superoxide in the rat aorta was also estimated by quantification of its effect on carbachol relaxation. This relaxation was diminished when endogenous superoxide dismutase was blocked by diethyldithiocarbamic acid. This blockade reduced the relaxation by 51.2±5.2% in SHRSP aortas and by only 22.0±8.2% (
P
=.015) in WKY aortas. Data from these diverse systems are in agreement that superoxide production is excessive in SHRSP tissues. This excess superoxide, by scavenging endothelial nitric oxide, could contribute to the increased vascular smooth muscle contraction and hence to the elevated total peripheral resistance of these rats.
A Consensus View on the Technique of Ambulatory Blood Pressure Monitoring
Authors: Staessen Jan A. , Fagard Robert , Thijs Lutgarde , Amery Antoon
Published: June 2012

Abstract
This review, based on the Fourth International Consensus Conference on Ambulatory Blood Pressure Monitoring (Leuven, Belgium, 1994), deals with the technical aspects of ambulatory blood pressure monitoring. Ambulatory blood pressure monitoring by noninvasive intermittent techniques is widely used despite artifacts due to cuff size, movement, body position, short-term blood pressure variability, and interference with sleep. The performance of the currently available monitors under truly ambulatory conditions and during exercise remains a matter of debate, as are the procedures required to validate portable monitors under these circumstances. There is general agreement that whenever a monitor is to be used in special populations, such as older subjects or pregnant women, or in special conditions, such as exercise, a specific demonstration of its accuracy in these defined subgroups or conditions is warranted. Whether the auscultatory or oscillometric method is preferred remains controversial because each technique has specific advantages and disadvantages and because both can provide accurate results. Most experts in the field strongly believe that manufacturers should disclose the algorithms of their devices and that they should specify all changes made to the hardware and software of a previously validated monitor. Finally, the development of the volume-clamp method, which makes continuous noninvasive registration of blood pressure at the finger possible in both stationary and ambulatory conditions, opens new perspectives in research, in particular in relation to short-term blood pressure variability.
Combinations of Potassium, Calcium, and Magnesium Supplements in Hypertension
Authors: Sacks Frank M. , Brown Lisa E. , Appel Lawrence , Borhani Nemat O. , Evans Denis , Whelton Paul
Published: June 2012

Abstract
Dietary intakes of potassium, calcium, and magnesium have each been reported to lower blood pressure, but the extent of blood pressure reduction in epidemiological studies and clinical trials has tended to be small and inconsistent. We hypothesized that combinations of these mineral supplements would lower blood pressure and that the reductions would be greater than that usually reported in studies of each cation alone. One hundred twenty-five patients (82 men and 43 women) with untreated mild or borderline hypertension were randomly assigned to daily treatment with one of the following four regimens: 60 mmol potassium and 25 mmol (1000 mg) calcium, 60 mmol potassium and 15 mmol (360 mg) magnesium, calcium and magnesium, or placebo. Standardized clinic blood pressure measurements were obtained on 3 days at baseline and after 3 and 6 months of treatment. At baseline, systolic and diastolic blood pressures (mean±SD) were 139±12 and 90±4 mm Hg, respectively, and dietary intakes of potassium, calcium, and magnesium were 77±32, 19±13, and 12±52 mmol/d, respectively. The mean differences (with 95% confidence intervals) of the changes in systolic and diastolic blood pressures between the treatment and placebo groups were not significant: −0.7 (−4.3 to +2.9) and −0.4 (−2.9 to +2.1) for potassium and calcium, −1.3 (−4.4 to +1.8) and 0.4 (−2.5 to +3.3) for potassium and magnesium, and +2.1 (−1.8 to +6.0) and +2.2 (−1.0 to +5.4) for calcium and magnesium. In conclusion, this trial provides little evidence of an important role of combinations of cation supplements in the treatment of mild or borderline hypertension.
Decrease in Intra-Abdominal Visceral Fat May Reduce Blood Pressure in Obese Hypertensive Women
Authors: Kanai Hideyuki , Tokunaga Katsuto , Fujioka Shigenori , Yamashita Shizuya , Kameda-Takemura Kaoru , Matsuzawa Yuji
Published: June 2012

Abstract
We investigated the relationship between changes in blood pressure and fat distribution after a 12-week low-calorie diet in 26 obese hypertensive women whose average age was 50±13 years, mean body mass index was 33.7±3.1 kg/m
2
, and mean blood pressure was 112±9 mm Hg. As an index of intra-abdominal fat accumulation, we used the ratio of the intra-abdominal visceral fat area to subcutaneous fat area, determined by a computed tomographic section at the level of the umbilicus. Subjects lost a mean of 9.4±4.1 kg on a 1200-kcal (5040-kJ) diet for 12 weeks. Their mean blood pressure fell from 112±9 to 101±12 mm Hg (
P
<.001). The ratio of the visceral to subcutaneous fat area was significantly reduced after weight reduction from 0.56±0.33 to 0.45±0.27 (
P
<.02). Fasting plasma glucose and plasma glucose area after a 75-g oral glucose tolerance test also were significantly reduced by weight reduction. The change in mean blood pressure after weight reduction was not correlated with the change in body weight or body mass index but was correlated with the reduction in visceral fat area or ratio of visceral fat to subcutaneous fat area. Changes in mean blood pressure also were correlated with changes in fasting plasma glucose levels and the plasma glucose area determined by 75-g oral glucose tolerance test. Results indicate that a decrease in intra-abdominal visceral fat, rather than simply of body weight, may reduce blood pressure in obese hypertensive subjects. The mechanism may involve an improvement in glucose tolerance caused by weight reduction.
Nocturnal Fall of Blood Pressure and Silent Cerebrovascular Damage in Elderly Hypertensive Patients
Authors: Kario Kazuomi , Matsuo Takefumi , Kobayashi Hiroko , Imiya Masahiro , Matsuo Miyako , Shimada Kazuyuki
Published: June 2012

Abstract
To study the relation between diurnal blood pressure variations and silent cerebrovascular damage, we performed both 24-hour ambulatory blood pressure monitoring and brain magnetic resonance imaging in 131 elderly asymptomatic hypertensive patients. Silent cerebrovascular damage was identified by the magnetic resonance imaging findings of lacunae (low intensity in T
1
-weighted images and high intensity in T
2
-weighted images) and advanced periventricular hyperintense lesions (on T
2
-weighted images). The frequency of silent cerebrovascular damage in the 100 patients with sustained hypertension was greater than that in the 31 patients with white coat hypertension. We further classified the former group into nondippers (nocturnal reduction of systolic pressure by <10% of awake systolic pressure; n=46), dippers (reduction by ≥10% to <20%; n=38), and extreme dippers (reduction by ≥20%; n=16). The extent of silent cerebrovascular damage was least severe in the dipper group (
P
<.05). This J-shaped relation was not found either with the cardiac hypertrophy detected by electrocardiography or with the renal damage assessed by urinary albumin excretion. More than half of the extreme dippers were patients with isolated systolic hypertension, and this prevalence was significantly greater than that in dippers or in nondippers (21% and 30%, respectively). Extreme dippers also had greater variability of pressure (standard deviation of awake systolic pressure) than dippers. Our results indicate that in addition to nondipping, extreme dipping (marked nocturnal fall of blood pressure) should be considered a type of abnormal diurnal blood pressure variation in elderly patients with hypertension who are likely to have advanced silent cerebrovascular damage.
Direct In Situ Measurement of Nitric Oxide in Mesenteric Resistance Arteries
Authors: Tschudi Marcel R. , Mesaros Stefan , Lüscher Thomas F. , Malinski Tadeusz
Published: June 2012

Abstract
The endothelium plays a critical role in maintaining vascular tone by releasing vasoconstrictor and vasodilator substances. Endothelium-derived nitric oxide is a vasodilator that can be rapidly inactivated by superoxide (reaction rate constant, K=3.6×10
9
L/mol per second). The measurement of nitric oxide concentration in biological systems is a challenging analytic problem because nitric oxide is also rapidly inactivated by Fe(II), Fe(III), and O
2
, all of which are found in great abundance in biological systems. To date, no currently used instrumental technique has been suitable for direct in situ measurement of NO in isolated resistance arteries. We designed the present study to perform for the first time direct in situ measurements of NO in rat mesenteric resistance arteries and to delineate the effects of hypertension on the release of NO and/or its interaction with superoxide. We describe here an adaptation of the recently published design of a porphyrinic sensor for direct in vitro measurement of NO in a single cell. The most significant advantage of this modified porphyrinic microsensor is that its small size makes it ideal for NO measurement in resistance arteries with an internal diameter of 200 μm or less. Small segments of the third-order branch of the mesenteric artery were isolated from normotensive Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats and placed in an organ chamber filled with Hanks’ balanced salt solution buffer (2 mL, 37°C). The tip of the porphyrinic microsensor was inserted into the lumen of an isolated vascular ring, and NO release was monitored in situ after maximal stimulation of NO synthase with the receptor-independent agonist calcium ionophore A23187 (10 μmol/L). Maximal surface concentration of NO measured after A23187 administration was significantly smaller in 15-week-old hypertensive rats (0.28±0.03 μmol/L, n=10) than in age-matched normotensive rats (0.38±0.03 μmol/L, n=10,
P
<.03). However, in the presence of the superoxide scavenger superoxide dismutase (100 U/mL), the peak NO level from the hypertensive rats was 0.37±0.04 μmol/L (n=10), which was comparable to that observed for the normotensive rats in the absence and presence of superoxide dismutase. In summary, our results demonstrate that in rat mesenteric resistance arteries hypertension is associated with increased NO decomposition by superoxide, whereas NO release remains unaffected. This may be important in the pathogenesis of hypertension and its cardiovascular complications.
Cardiovascular Effects of Nitric Oxide in the Brain Stem Nuclei of Rats
Authors: Tseng Ching-Jiunn , Liu Hui-Ya , Lin Hui-Ching , Ger Luo-Ping , Tung Che-Se , Yen Mao-Hsiung
Published: June 2012

Abstract
Nitric oxide, synthesized from the semiessential amino acid
l
-arginine by nitric oxide synthase, is a remarkable regulatory molecule and plays an important role in physiological functions. However, the physiological role of nitric oxide in cardiovascular regulation by the central nervous system is not well understood. In this study we investigated the cardiovascular effects of nitric oxide in the lateral ventricle, nucleus tractus solitarii, area postrema, and rostral ventrolateral medulla in urethane-anesthetized male Sprague-Dawley rats. Microinjection of
N
G
-monomethyl-
l
-arginine, a nitric oxide synthase inhibitor, into the cerebral ventricle of rats elicited a dose-dependent increase in blood pressure and heart rate. This suggests that nitric oxide may be involved in central cardiovascular regulation. Unilateral microinjection (60 nL) of
l
-arginine (1 to 100 nmol) into the nucleus tractus solitarii and rostral ventrolateral medulla produced prominent dose-related depressor and bradycardic effects and reduced renal sympathetic nerve activity. However,
l
-arginine had no significant cardiovascular effects in the area postrema. In addition, 4 to 6 hours after intravenous injection of bacterial endotoxin-lipopolysaccharide (10 mg/kg), there was a time-related potentiation of the
l
-arginine–induced depressor and bradycardic effects in the nucleus tractus solitarii. These results indicate that nitric oxide is involved in central cardiovascular regulation. The depressor effect of nitric oxide in the nucleus tractus solitarii and rostral ventrolateral medulla may be through inhibition of renal sympathetic nerve activity.
Vascular Structure and Expression of Endothelin-1 Gene in L-NAME–Treated Spontaneously Hypertensive Rats
Authors: Sventek Pavol , Li Jin-S. , Grove Kevin , Deschepper Christian F. , Schiffrin Ernesto L.
Published: June 2012

Abstract
Inhibition of nitric oxide synthase by
l
-arginine analogues is associated with elevation of blood pressure in rats. Deoxycorticosterone acetate (DOCA)-salt hypertensive rats and DOCA-salt–treated spontaneously hypertensive rats (SHR) overexpress the endothelin-1 gene in blood vessels, and this is associated with severe vascular hypertrophy, whereas SHR do not overexpress endothelin-1 and exhibit limited vascular hypertrophy. In this study malignant hypertension was induced in SHR by chronic administration of the
l
-arginine analogue
N
G
-nitro-
l
-arginine methyl ester (L-NAME), a potent inhibitor of nitric oxide synthase, to determine whether malignant hypertension would result in endothelin-1 gene overexpression in blood vessels and in greater severity of vascular hypertrophy, as found in malignant DOCA-salt–treated SHR. L-NAME treatment induced malignant hypertension in SHR, with a systolic blood pressure of 246±2 mm Hg, compared with 211±2 mm Hg (
P
<.01) in untreated SHR. Plasma renin activity was very high in L-NAME–treated SHR, and their plasma immunoreactive endothelin concentration was slightly but significantly elevated (
P
<.01). After 3 weeks of treatment, aortic and to a lesser degree mesenteric artery weights were significantly increased in L-NAME–treated SHR compared with untreated SHR. However, cardiac weight and the media cross-sectional area or media width–to–lumen diameter ratio of small arteries from the coronary, renal, mesenteric, or femoral vasculature were not increased in L-NAME–treated SHR in comparison with untreated SHR. The abundance of endothelin-1 mRNA measured by Northern blot analysis was significantly increased in L-NAME–treated SHR in aorta and with less magnitude in the mesenteric arterial tree. The absence of accentuation of cardiac and small artery hypertrophy in malignant hypertension in L-NAME–treated SHR, despite enhanced expression of the endothelin-1 gene in blood vessels, may suggest a direct or indirect inhibitory effect of L-NAME on cardiovascular growth, probably independent of its effects on nitric oxide synthase, counterbalanced in aorta and large mesenteric arteries by the hypertrophic effect of enhanced vascular endothelin-1 gene expression. These results also suggest a role for blood pressure and potentially for nitric oxide in the regulation of endothelin-1 gene expression in blood vessels.
Time-Voltage Area of the QRS for the Identification of Left Ventricular Hypertrophy
Authors: Okin Peter M. , Roman Mary J. , Devereux Richard B. , Kligfield Paul
Published: June 2012

Abstract
Standard electrocardiographic criteria have exhibited poor sensitivity for left ventricular hypertrophy at acceptable levels of specificity and perform less well in women than men, even when sex-specific criteria are used. The time-voltage integral of the horizontal plane vector QRS complex can improve identification of hypertrophy in men, but performance of this approach in women and the effect of sex-specific criteria on accuracy have not been examined. To evaluate the accuracy of the time-voltage integral of the QRS complex for the identification of left ventricular hypertrophy in women and to examine the effect of sex- and non–sex-specific criteria on test performance, we obtained standard 12-lead and orthogonal-lead signal-averaged electrocardiograms and echocardiograms in 175 control subjects without hypertrophy (43 women and 132 men) and 75 patients with hypertrophy (26 women and 49 men) defined by echocardiographic criteria (indexed left ventricular mass >110 g/m
2
in women and >125 g/m
2
in men). Voltage of the QRS complex was integrated over the total QRS duration in leads X and Z for calculation of the time-voltage integral of the horizontal plane vector complex. With the use of a partition of 99.2 μV·s with a specificity of 98% in the entire normal group, sensitivity of the horizontal plane vector integral was significantly lower in women than men (31% versus 71%,
P
<.001). In contrast, use of sex-specific partitions of 75.4 μV·s in women and 99.2 μV·s in men with matched 98% specificity significantly improved sensitivity in women to 81% (
P
<.001), with no change in sensitivity in men (71%). Comparison of receiver operating characteristic curves with the use of sex-specific criteria demonstrated no significant difference in overall performance of the horizontal plane vector integral between men and women. The 81% and 71% sensitivities of the sex-specific horizontal plane vector integral were significantly greater than the 27% to 58% sensitivities of sex-specific 12-lead electrocardiographic criteria in this population. Thus, sex-specific criteria significantly improve performance of the time-voltage integral of the QRS for the identification of left ventricular hypertrophy in women, with no loss of accuracy in men. Use of the time-voltage integral can improve the accuracy of the electrocardiogram for the identification of left ventricular hypertrophy in both women and men.
Endothelin-1 and Its Receptor in Hypertrophic Cardiomyopathy
Authors: Hasegawa Koji , Fujiwara Hisayoshi , Koshiji Masatoshi , Inada Tsukasa , Ohtani Seiji , Doyama Kiyoshi , Tanaka Masaru , Matsumori Akira , Fujiwara Takako , Shirakami Gotaro , Hosoda Kiminori , Nakao Kazuwa , Sasayama Sigetake
Published: June 2012

Abstract
Endothelin-1, a potent vasoconstrictor produced by vascular endothelial cells, activates the hypertrophic program in cultured heart muscle cells. However, the role of endothelin-1 in cardiac hypertrophy in humans is unknown. Therefore, we studied hypertrophic cardiomyopathy patients with normal pulmonary arterial pressure, in whom cardiac hypertrophy is a specific feature of the disease. Radioimmunoassay with a monoclonal antibody to human endothelin-1 showed that the plasma level of immunoreactive endothelin was more than twofold higher in hypertrophic cardiomyopathy patients than in control subjects (
P
<.005). In situ hybridization analysis of endomyocardial biopsy specimens showed positive signals of endothelin-1 type A receptor mRNA in ventricular myocytes of all specimens. The receptor expression in ventricular myocytes was similar between hypertrophic cardiomyopathy patients and control subjects. We propose that endothelin-1 might represent an important factor involved in hypertrophic cardiomyopathy. Whether endothelin-1 plays a causal role in cardiac hypertrophy or is a marker of its occurrence needs to be clarified.
Activation of Angiotensin-Generating Systems in the Developing Rat Kidney
Authors: Yosipiv Igor V. , El-Dahr Samir S.
Published: June 2012

Abstract
The present study was designed to determine the developmental changes in intrarenal angiotensin (Ang) peptides in the rat. Kidney Ang I and II levels were threefold and sixfold higher in newborn than adult kidneys, respectively (Ang I, 678±180 versus 243±38 fmol/g,
P
<.01; Ang II, 667±75 versus 103±6 fmol/g,
P
<.001). Intrarenal Ang II levels correlated positively with the temporal changes in renin gene expression (
r
=.93,
P
<.001). However, no correlation was found between renal Ang II content and angiotensin-converting enzyme (ACE) expression during development, which prompted us to evaluate whether renal enzymes, other than renin and ACE, contribute to Ang II formation in the developing kidney. Angiotensin peptide levels were measured in newborn and adult kidney homogenates incubated with human angiotensinogen (a poor rat renin substrate) for 30 minutes at 37°C. Inhibitors of aspartyl proteases and metalloproteases were ineffective in preventing the formation of Ang II in either newborn or adult kidneys. However, addition of the serine protease inhibitors soybean trypsin inhibitor and phenylmethylsulfonyl fluoride inhibited Ang II generation in the newborn kidneys only. In contrast, Ang I generation was not affected by inhibition of serine proteases in either newborn or adult kidneys. We conclude that Ang I and II synthesis is activated in the developing rat kidney. In addition to renin and ACE, the newborn rat kidney expresses serine protease activity that is capable of generating Ang II directly from angiotensinogen. This putative enzyme is induced in the newborn kidney and may cooperate with renin in the activation of Ang II synthesis during early development.
Localization of α2A- and α2B-Adrenergic Receptor Subtypes in Brain
Authors: Tavares Agostinho , Handy Diane E. , Bogdanova Natalia N. , Rosene Douglas L. , Gavras Haralambos
Published: June 2012

Abstract
Recent studies have shown that all three subtypes of α
2
-adrenergic receptor (α
2
-AR) are found in brain. The purpose of this study was to map the subtype localization of the α
2A
- and α
2B
-ARs in brain structures. RNase protection shows that both the α
2A
- and α
2B
-ARs are detectable in cortex, cerebellum, pons-medulla, and hypothalamus. We tested probes derived from the α
2A
- and α
2B
-AR cDNAs on cell lines that express each of the α
2
-AR subtypes to establish the subtype specificity of these probes for in situ hybridization. Then we used the α
2A
- and α
2B
-AR probes for in situ hybridization on sagittal and coronal sections of rat brain. Both α
2A
and α
2B
mRNA were detected throughout the brain. Overall, there appears to be a greater expression of message for α
2A
- than α
2B
-AR in most brain areas, with the exception of the thalamus. Developing these probes for in situ hybridization is an important step for further studies on the exact role of the α
2
-AR subtypes in neurons that modulate cardiovascular function.