bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Basal and Stimulated Release of Nitric Oxide in the Regulation of Radial Artery Caliber in Humans
Authors: Joannides Robinson , Richard Vincent , Haefeli Walter E. , Linder Lilly , Lüscher Thomas F. , Thuillez Christian
Published: June 2012

Abstract
Although it is well established that nitric oxide contributes to the regulation of resistance arterial tone in humans, its role at the level of large arteries is less clear. Therefore, we assessed in healthy volunteers the effects of local administration of the inhibitor of nitric oxide synthesis
N
G
-monomethyl-
l
-arginine (L-NMMA) on basal radial artery diameter (transcutaneous A-mode echotracking) and radial blood flow (Doppler) as well as on the radial response to acetylcholine and the nitric oxide donor sodium nitroprusside. A catheter was inserted into the brachial artery for measurement of arterial pressure and infusion of L-NMMA (2, 4, and 8 μmol/min for 5 minutes, n=11), acetylcholine (3, 30, 300, and 900 nmol/min for 3 minutes, n=8), and nitroprusside (2.5, 5, 10, and 20 nmol/min for 3 minutes, n=6). None of the treatments affected arterial blood pressure or heart rate. L-NMMA dose-dependently decreased radial blood flow (from 31±6 to 17±3 10
−3
L/min after 8 μmol/min,
P
<.01) but did not affect radial artery diameter (from 2.93±0.11 to 2.90±0.14 mm). Acetylcholine dose-dependently increased radial blood flow (154±43% after 900 nmol/min) and radial artery diameter (16±4%), and both effects were markedly reduced after L-NMMA (increase in radial blood flow and radial artery diameter: 22±20% and 3±2%, respectively; both
P
<.01 versus controls). Nitroprusside also dose-dependently increased radial artery diameter (14±4% after 20 nmol/min) but only moderately affected radial blood flow (47±21%). L-NMMA markedly increased the effects of nitroprusside on radial artery diameter (26±2%,
P
<.01 versus controls) but not on radial blood flow (66±21%,
P
=NS versus controls). These experiments demonstrate for the first time that large peripheral arteries vasodilate in response to acetylcholine in vivo through the release of endogenous nitric oxide. The increased sensitivity to nitrovasodilators after L-NMMA suggests the existence of a basal release of nitric oxide at the level of large peripheral arteries. However, the lack of a decrease in diameter after L-NMMA might be explained by the presence of compensating vasodilator mechanisms occurring at the level of large arteries after inhibition of nitric oxide synthesis.
Isolated Elevation of Diastolic Blood Pressure
Authors: Blank Seymour G. , Mann Samuel J. , James Gary D. , West James E. , Pickering Thomas G.
Published: June 2012

Abstract
Not infrequently, blood pressure measurement by the standard auscultatory technique yields a normal systolic pressure with an elevated diastolic pressure. The relatively narrow pulse pressure of such a measurement raises concern about the accuracy of the blood pressure measurement. The purpose of this study was to assess the accuracy of auscultatory blood pressure measurements in patients with an uncommonly narrow pulse pressure, particularly patients with an elevated diastolic but normal systolic pressure. Auscultatory blood pressure measurements were compared with an objective noninvasive standard, called K2 analysis, which has been shown to be more accurate than the auscultatory technique. Blood pressure was measured simultaneously by auscultatory and K2 techniques in 175 subjects. Comparisons were performed (1) in the group as a whole, (2) in four clinical subgroups (normotensive [<140/<90 mm Hg, n=69], hypertensive [≥140/≥90 mm Hg, n=53], isolated systolic hypertensive [≥140/<90 mm Hg, n=38], and isolated diastolic hypertensive [<140/≥90 mm Hg, n=15]), and (3) in two subgroups whose ratio of pulse pressure to diastolic pressure was greater than or equal to 0.45 (n=151) or less than 0.45 (n=24). Subjects in the isolated diastolic hypertensive group and in the group with a pulse pressure ratio less than 0.45 were considered to have a narrow pulse pressure. In the group as a whole, consistent with previous auscultatory-K2 comparisons, systolic pressure was slightly higher and diastolic pressure slightly lower when measured by K2 versus the auscultatory technique (auscultatory, 145/85 mm Hg; K2, 147/83 mm Hg). For diastolic pressure auscultatory measurements averaged 7 mm Hg greater than K2 in the isolated diastolic hypertensive group (94±4 versus 87±5 mm Hg) but were less than 3 mm Hg (greater) in the other three groups (
P
<.0004). For systolic pressure, differences were less than 3 mm Hg in all four clinical groups. Auscultatory-K2 differences of diastolic pressure exceeding 5 mm Hg (and 10 mm Hg) were seen in 73.3% (and 40.0%) of isolated diastolic hypertensive subjects versus only 14.5% (2.9%) of normotensive subjects, 22.6% (1.9%) of hypertensive subjects, and 7.9% (2.6%) of isolated systolic hypertensive subjects (
P
<.0001). Similarly, the auscultated diastolic pressure exceeded the K2 measurement by at least 5 mm Hg (and 10 mm Hg) in 62.5% (29.2%) of subjects with a pulse pressure ratio less than 0.45 versus 13.9% (2.0%) in subjects with a ratio greater than or equal to 0.45 (
P
<.0001). Auscultatory-K2 differences of diastolic pressure were strongly and inversely related to the pulse pressure ratio (
r
=−.68,
P
<.0001) independent of sex, race, or body weight. In conclusion, when the pulse pressure is particularly narrow, auscultation frequently overestimates the true diastolic pressure by 5 mm Hg or more. The treatment implications of this finding, particularly in patients with elevated diastolic but normal systolic pressure, merit further study.
Enhanced Immunoglobulin Formation of Immortalized B Cells From Hypertensive Patients
Authors: Rosskopf Dieter , Hartung Kathrin , Hense Jörg , Siffert Winfried
Published: June 2012

Abstract
Increased immunoglobulin levels and leukocyte counts have frequently been reported in essential hypertension. The underlying mechanisms, however, have remained obscure. Enhanced Na
+
-H
+
exchanger activity is another frequently observed abnormality in essential hypertension that persists in immortalized B lymphoblasts and coincides with enhanced proliferation. We investigated the capacity of B lymphoblasts from essential hypertensive patients to synthesize and secrete immunoglobulins. Six B cell lines from essential hypertensive patients with enhanced Na
+
-H
+
exchanger phenotype and six cell lines from normotensive subjects were studied. Lymphocyte markers were visualized by immunostaining. Immunoglobulin secretion was analyzed by enzyme-linked immunosorbent assay. These cell lines did not differ with respect to B cell markers. In response to 100 nmol/L platelet-activating factor, cells from hypertensive patients proliferated distinctly more quickly and their cell number increased by 3.9±0.4-fold (mean±SD) within 4 days, whereas the number of cells from normotensive subjects increased by only 2.6±0.1-fold. Furthermore, platelet-activating factor induced average increases in IgM and IgG formation of 13.3- and 5.4-fold, respectively, in lymphoblasts from hypertensive patients, which was significantly higher than increases in cells from normotensive subjects (1.4- and 1.2-fold, respectively). Thus, lymphoblasts from hypertensive patients proliferate more quickly and secrete more immunoglobulins in response to a physiological stimulus in vitro. This may contribute to the raised immunoglobulin levels and leukocyte counts reported in vivo.
Blood Pressure in Genetically Hypertensive Rats
Authors: Davidson Anne O. , Schork Nicholas , Jaques Bryon C. , Kelman Andrew W. , Sutcliffe Roger G. , Reid John L. , Dominiczak Anna F.
Published: June 2012

Abstract
We used a cross between the stroke-prone spontaneously hypertensive rat (SHRSP) strain and the Wistar-Kyoto (WKY) normotensive strain to elucidate the genetic basis of hypertension. Previous studies have reported conflicting evidence for the contribution of the Y chromosome to hypertension in these models. To investigate further the role of the Y chromosome in hypertension, we performed two large reciprocal crosses: one with the SHRSP as a male progenitor of the cross, yielding 60 F
2
rats, and another with the WKY as a male progenitor, yielding 83 F
2
rats. The resulting F
2
hybrids were phenotyped with the use of a radiotelemetry system (Data Sciences) for measurement of systolic, diastolic, and mean arterial pressures as well as heart rate and motor activity continuously for 96 hours at baseline and after 1% NaCl was added to the rats’ drinking water for 12 days. Male F
2
hybrids with the SHRSP grandfather had significantly higher average systolic, diastolic, and mean arterial pressures at baseline compared with male F
2
hybrids with the WKY grandfather (188.7±18.1 versus 168.9±11.5, 130.3±14 versus 115.7±7.3, and 159.1±15.8 versus 141.5±9.4 mm Hg, respectively). These differences were also observed after salt loading (197.9±22.1 versus 176.8±11.7, 136.5±17.3 versus 120.7±7.6, and 166.7±19.5 versus 148±9.7 mm Hg, respectively;
P
<.0001 for each comparison). These results suggest that the SHRSP Y chromosome contains a locus or loci that contribute to hypertension in SHRSP/WKY F
2
hybrids.
Hemodynamic Alterations in Hypertensive Obese Rabbits
Authors: Carroll Joan F. , Huang Min , Hester Robert L. , Cockrell H. Kathy , Mizelle Leland
Published: June 2012

Abstract
There is little information on changes in overall and regional hemodynamics in obesity-associated hypertension. Therefore, the purpose of this study was to determine alterations in overall and regional blood flows and resistances in adipose and nonadipose tissues in a new model of obesity-associated hypertension in rabbits. Sixteen female New Zealand White rabbits were fed either a maintenance or high-fat diet; after 8 to 12 weeks cardiac output and regional blood flows were measured with the use of radioactive microspheres. Obese rabbits (5.22±0.14 versus 3.66±0.04 kg) had higher blood pressure (113±3 versus 95±1 mm Hg), cardiac output (812±59 versus 593±47 mL/min), and heart rate (269±12 versus 219±9 beats per minute) and lower overall peripheral resistance (0.14±0.01 versus 0.17±0.01 mm Hg/[mL/min]) than lean rabbits. Compared with lean controls, obese rabbits had higher weights of the ventricles, kidneys, liver, ovaries, adrenals, diaphragm, and spleen. Absolute blood flows were greater in the ventricles, kidneys, lungs, and ovaries, but differences were minimized when flows were normalized for organ weight. Adipose tissue flow per gram weight was significantly lower and resistance higher in obese rabbits. However, calculated total adipose tissue flow was higher in obese rabbits (86 versus 45 mL/min). Absolute resistances were lower in the left ventricle, kidneys, and large intestine, but when resistances were indexed for organ weight, kidney resistance tended to be higher in obese rabbits. These results indicate that even short periods of obesity-associated hypertension result in marked overall and regional hemodynamic changes.
Angiotensin-Converting Enzyme Inhibition and Radial Artery Compliance in Patients With Congestive Heart Failure
Authors: Giannattasio Cristina , Failla Monica , Stella Maria L. , Mangoni Arduino A. , Turrini Davide , Carugo Stefano , Pozzi Massimo , Grassi Guido , Mancia Giuseppe
Published: June 2012

Abstract
Congestive heart failure is characterized by a clear-cut impairment of arterial compliance of medium-sized arteries, but whether this alteration is irreversible or can be favorably affected by cardiovascular drugs currently used in congestive heart failure treatment is unknown. We studied 9 congestive heart failure patients (New York Heart Association class II; age, [mean±SEM] 60.7±3.3 years) receiving diuretic and digitalis treatment in whom arterial compliance was assessed at the level of the radial artery by an echotracking device capable of measuring the arterial diameter along the entire cardiac cycle. Beat-to-beat arterial blood pressure was concomitantly measured by a Finapres device that allowed diameter-pressure curves and compliance-pressure curves (Langewouters’ formula) to be calculated for the entire systolic-diastolic blood pressure range. Arterial compliance was expressed as the area under the compliance-pressure curve normalized for pulse pressure (compliance index). Data were collected before and after 4 and 8 weeks of oral administration of benazepril (10 mg/day). Ten healthy subjects were studied before and after an observational period of 4 weeks (5 subjects) or 8 weeks (5 subjects), and 9 age-matched mildly essential hypertensive subjects studied before and after 4 to 12 weeks of benazepril administration served as control subjects. In congestive heart failure patients, baseline compliance index was significantly less than in normotensive and hypertensive subjects. However, the compliance index showed a marked increase after 4 weeks of benazepril administration (+95.7±24.9%,
P
<.05); the increase was also marked after 8 weeks of angiotensin-converting enzyme inhibitor treatment (+77.7±4.2%,
P
<.05). At this time the compliance values of the congestive heart failure patients were not different from those of the healthy and hypertensive groups, in which the observational period and angiotensin-converting enzyme inhibitor administration, respectively, had brought no change in compliance. Similar results were observed when compliance index was calculated for the blood pressure range shared by the three groups (isobaric compliance). These data provide the first evidence that the impairment of arterial compliance occurring in congestive heart failure can be favorably affected by the addition of an angiotensin-converting enzyme inhibitor to the treatment regimen. This has favorable implications for the cardiovascular functions adversely affected by a reduced arterial compliance (eg, cardiac work and oxygen consumption, coronary perfusion, and arterial baroreflex).
Underestimation of Vasodilator Effects of Nitroglycerin by Upper Limb Blood Pressure
Authors: Takazawa Kenji , Tanaka Nobuhiro , Takeda Kazuhiro , Kurosu Fujio , Ibukiyama Chiharu
Published: June 2012

Abstract
To determine why upper limb blood pressure measurement underestimates the vasodilator effects of nitroglycerin on lowering ascending aortic systolic pressure, we studied 24 patients (58±11 years, mean±SD). Ascending aortic pressure and radial artery pulse calibrated by cuff blood pressure measurement at the brachial artery were recorded simultaneously before and 5 minutes after sublingual administration of 0.3 mg nitroglycerin. Waves were analyzed by a signal processor, and the fourth derivative wave was used to find the early (S1) and late (S2) systolic shoulders (S1 corresponds to the second zero crossing and S2 to the third zero crossing). Before nitroglycerin administration, maximal systolic pressure in the ascending aorta (141±21 mm Hg) coincided with the late systolic peak in all patients, and in most patients (21 of 24) maximal systolic pressure in the radial artery (140±19 mm Hg) coincided with the early systolic peak. Maximal systolic pressure decreased more in the ascending aorta than in the radial artery (22±13 and 11±11 mm Hg, respectively;
P
<.001). However, the reduction in the shoulder of late systolic pressure in the radial artery (24±13 mm Hg) clearly indicated the reduction in maximal systolic pressure (late systolic peak) in the ascending aorta. The augmentation index of the ratio of the height of late systolic pressure to early systolic pressure fell proportionally (
r
=.74,
P
<.001) in the radial artery (from 0.88±0.13 to 0.60±0.11) and in the ascending aorta (from 1.57±0.25 to 1.26±0.24), which indicated the reduction in late systolic pressures. These data suggest that ordinary peripheral artery blood pressure measurement underestimates the vasodilation effects of nitroglycerin on the ascending aorta because without arterial pulse measurement it cannot show changes in late systolic pressure.
Short- and Long-term Effects of Antihypertensive Drugs on Arterial Reflections, Compliance, and Impedance
Authors: Ting Chih-Tai , Chen Chen-Huan , Chang Mau-Song , Yin Frank C.P.
Published: June 2012

Abstract
This article reviews our work on the effects of different classes of antihypertensive agents on the hemodynamic alterations in essential human hypertension. Short-term studies were done during cardiac catheterization in young normotensive subjects (mean age, 33 years; range, 19 to 40) and several different age-matched (range, 25 to 53 years) groups of patients with essential hypertension. Aortic impedance, resistance, wave reflections, and compliance were calculated from high-fidelity recordings of ascending aortic pressure and flow signals during baseline and after nitroprusside, propranolol followed by phentolamine, phentolamine, captopril, and nifedipine, respectively, at doses sufficient to normalize blood pressure in each hypertensive group. Propranolol exacerbated all the hemodynamic parameters; these effects were only partially overcome by phentolamine. Among the other agents only phentolamine did not completely normalize compliance, and only captopril did not completely normalize wave reflections. The long-term study was a randomized, double-blind comparison of fosinopril and atenolol in 79 normotensive subjects and 79 essential hypertensive patients. Baseline 24-hour ambulatory blood pressures and carotid artery tonometry to index wave reflections were performed in all subjects and in hypertensive patients after 8 weeks of therapy. Both fosinopril and atenolol normalized blood pressure and lowered the elevated augmentation index, but fosinopril had a significantly larger effect than atenolol. Both short- and long-term β-blockade did not have as beneficial an effect as the other agents. Thus, the differing hemodynamic effects of the various classes of antihypertensive agents might be a consideration in the choice of therapy.
Sodium-Proton Exchange and Primary Hypertension
Authors: Siffert Winfried , Düsing Rainer
Published: June 2012

Abstract
An enhancement of sodium-proton exchange in blood cells of patients with primary hypertension has been described by various investigators. The present review summarizes some of the most recent findings regarding the enhanced sodium-proton exchanger activity in primary hypertension and discusses the potential mechanisms that may contribute to or explain these findings. Novel evidence has been accumulated on the in vivo regulation of the sodium-proton exchanger in humans, and recent findings suggest that metabolic acidosis, high NaCl intake, and circulating hormones (eg, insulin) can enhance sodium-proton exchanger activity in blood cells. However, the relative roles of such exogenous factors in the stimulation of sodium-proton exchanger activity in primary hypertension remain questionable because enhanced sodium-proton exchanger activity persists in immortalized lymphoblasts from patients with primary hypertension after prolonged cell culture. Therefore, at least in a certain group of hypertensive subjects this abnormality cannot be due to metabolic or hormonal alterations of the “hypertensive” in vivo milieu but appears to be under genetic control. Available evidence strongly argues against intrinsic changes of the sodium-proton exchanger protein itself in primary hypertension, for example, a mutation in the encoding gene. Interestingly, immortalized cells from hypertensive subjects with enhanced sodium-proton exchanger activity display a distinctly enhanced proliferation pattern that appears to be independent of this ion transport. At present we speculate that enhanced sodium-proton exchanger activity and proliferation may represent indicators of a genetically fixed enhanced intracellular signal transduction in primary hypertension that may be caused by an increased activation of pertussis toxin–sensitive G proteins.
Suppressing Sympathetic Activation in Congestive Heart Failure
Authors: Manolis Athanasios J. , Olympios Christoforos , Sifaki Maria , Handanis Stelios , Bresnahan Margaret , Gavras Irene , Gavras Haralambos
Published: June 2012

Abstract
Neurohormonal activation with increased plasma renin activity and norepinephrine and vasopressin levels is characteristic of congestive heart failure and contributes to further decompensation and poor prognosis. We treated 20 such patients with the centrally acting sympathoinhibitory drug clonidine 0.15 mg BID and obtained hemodynamic measurements by cardiac catheterization and plasma neurohormone levels before and 2 to 3 hours after the first dose; in 7 patients, these measurements were taken again after 1 week of therapy. The initial dose produced significant decreases of 8% in mean arterial pressure, 23% in right atrial pressure, 21% in pulmonary capillary wedge pressure, 19% in mean pulmonary artery pressure, and 12% in heart rate; a 17% increase in stroke volume; and no significant changes in cardiac output and systemic vascular resistance. All changes remained virtually constant after 1 week. Plasma norepinephrine decreased by 28% after the initial dose and 62% after 1 week (
P
<.01), whereas plasma renin activity remained essentially unchanged. Plasma vasopressin tended to increase, its levels being inversely correlated with those of posttreatment norepinephrine (
r
=−.48,
P
<.03). Patients with baseline norepinephrine levels >0.400 ng/mL had significantly poorer baseline hemodynamic parameters and tended to show more improvement with clonidine, although their data remained significantly worse than patients whose baseline norepinephrine was within the normal range. Sympathetic suppression with clonidine in congestive heart failure reduces preload, heart rate, and arterial pressure, all indexes of myocardial energy demand; the lack of significant reduction in systemic vascular resistance and increase in cardiac output might be attributable in part to enhanced release of vasopressin. The data suggest that suppression of activated pressor neurohormones is a rational approach to treatment of congestive heart failure.
Chronic Angiotensin-Converting Enzyme Inhibition and Endothelial Function of Rat Aorta
Authors: Berkenboom Guy , Brékine Dmitri , Unger Philippe , Grosfils Katrina , Staroukine Michel , Fontaine Jeanine
Published: June 2012

Abstract
To determine whether chronic angiotensin-converting enzyme (ACE) inhibition produces functional changes in the aorta of normotensive rats, four groups of rats were studied in parallel for 6 weeks. Group 1 orally received ramipril 10 mg/kg per day for 6 weeks; group 2, ramipril 10 mg/kg per day for 4 weeks and then a cotreatment with ramipril and β
2
-kinin antagonist HOE140 500 μg/kg per day SC by injection for the remaining 2 weeks; group 3, hydralazine 100 mg/kg per day PO for 6 weeks; group 4 (control), subcutaneous injections of saline solution during the last 2 of 6 weeks. In aorta isolated from group 1 the relaxations induced by bradykinin, acetylcholine, and histamine were significantly potentiated compared with those of group 4. In group 3, despite a decrease in systolic blood pressure similar to that induced by ramipril treatment, the responses to these three endothelium-dependent vasodilators were not different from those of group 4. In group 2, bradykinin-induced relaxations were completely abolished whereas acetylcholine-induced and histamine-induced relaxations were similar to those of group 4. The inhibitory effect of the endothelium on serotonin-induced contractions was significantly increased in preparations of group 1 compared with those of groups 2 through 4. Indirect measurements of nitric oxide formation such as contractions evoked by
N
G
-monomethyl-
l
-arginine (L-NMMA) and aortic cGMP content were also significantly enhanced in preparations from group 1 compared with those of groups 2 and 4. Moreover, because the relaxations to nitroglycerin and nitroprusside were similar in groups 1, 2, and 4 an alteration of the guanylate cyclase activity by ramipril treatment is quite unlikely. Thus long-term treatment with ramipril potentiates the endothelium-dependent responses in the rat aorta by enhancing nitric oxide availability. This effect seems to involve an inhibition of bradykinin breakdown facilitating nitric oxide release via endothelial β
2
-receptors.
Enhanced Vascular Neuropeptide Y– Immunoreactive Innervation in Two Hypertensive Rat Strains
Authors: Fan Xin-Min , Hendley Edith D. , Forehand Cynthia J.
Published: June 2012

Abstract
Considerable evidence indicates an enhanced sympathetic innervation of resistance arterial smooth muscle in the spontaneously hypertensive rat (SHR) compared with its normotensive Wistar-Kyoto (WKY) control. In addition to sympathetic hyperinnervation, an increased vascular innervation by neuropeptide Y–containing fibers, which are known to exert a vasoconstrictive and trophic action in vascular smooth muscle, has also been described. In addition to genetic hypertension, the SHR expresses hyperactive behavior and hyperreactivity to stress. To determine whether the enhanced neuropeptide Y–immunoreactive vascular innervation is specifically associated with hypertension and/or these behavioral abnormalities, four genetically related, inbred rat strains were used: SHR, which are hypertensive and hyperactive; WKY rats, which are neither hypertensive nor hyperactive; WKHA, which are hyperactive but normotensive; and WKHT, which are hypertensive but not hyperactive. The present study demonstrated that whereas the hypertensive strains (SHR and WKHT) exhibited smooth muscle hypertrophy in both superior mesenteric and caudal arteries in adulthood (10 months) but not at a prehypertensive age (1 month), both arteries exhibited significantly increased neuropeptide Y–immunoreactive innervation at both ages. It was further observed that the mesenteric artery in WKHA, a normotensive strain, had significant smooth muscle hypertrophy at 10 months; however, neuropeptide Y innervation in this artery was no different from that of WKY controls. The findings indicate that there is a cosegregation of neuropeptide Y hyperinnervation of the vasculature with the hypertensive phenotype, evident as early as 1 month of life in the hypertensive strains, and this should be considered further as a contributory factor in genetic hypertension. Vascular smooth muscle hypertrophy, while evident in adult hypertensive rats, was also observed in the mesenteric artery (but not the caudal artery) of adult WKHA rats, suggesting that other factors besides genetic hypertension, possibly hyperreactivity to stress, are responsible for this specific hypertrophic change in WKHA rats.
Thromboxane A
2
and Vascular Smooth Muscle Cell Proliferation
Authors: Sachinidis Agapios , Flesch Markus , Ko Yon , Schrör Karsten , Böhm Michael , Düsing Rainer , Vetter Hans
Published: June 2012

Abstract
In the present study we describe the intracellular pathways for the transmission of growth signals by the potent vasoconstricting eicosanoids prostaglandin H
2
and thromboxane A
2
in smooth muscle cells from rat aorta. Carbocyclic thromboxane A
2
and U46619 are stable thromboxane A
2
mimetics acting at the common thromboxane A
2
/prostaglandin H
2
receptor. Carbocyclic thromboxane A
2
(10
−6
mol/L) induced an approximately 2.5-fold increase in [Ca
2+
]
i
above the basal value at 25 seconds. Maximal stimulation of the 42-kD mitogen-activated protein kinase isoform by both thromboxane A
2
mimetics occurred at 5 minutes. Both thromboxane A
2
mimetics at a concentration of 10
−6
mol/L induced the expression of c-
fos
and early growth response gene-1 (
egr-1
) mRNA, with a maximum at 30 minutes. Carbocyclic thromboxane A
2
(10
−6
mol/L) induced a 3.3-fold increase in [
3
H]thymidine incorporation into cell DNA above the basal value and produced a 3.5-fold elevation of platelet-derived growth factor-BB–dependent [
3
H]thymidine incorporation into cell DNA. Similar effects of U46619 (10
−6
to 10
−5
mol/L) alone and in combination with platelet-derived growth factor-BB on cell DNA synthesis were obtained. The thromboxane A
2
/prostaglandin H
2
receptor antagonist SQ29548 (10
−6
mol/L) completely suppressed the mitogenic effect of both thromboxane A
2
mimetics (10
−6
mol/L). Pertussis toxin (10 to 100 ng/mL) did not influence the mitogenic effects of the thromboxane A
2
mimetics. Carbocyclic thromboxane A
2
(10
−6
mol/L) and platelet-derived growth factor-BB (20 ng/mL) per se caused a 44% and 100% increase in cell number, respectively. In the presence of carbocyclic thromboxane A
2
(10
−6
mol/L), platelet-derived growth factor-BB induced a 152% increase in cell number. Similar results were obtained with U46619 alone or in combination with platelet-derived growth factor-BB.
Gene Expression of Angiotensin II Receptor in Blood Cells of Cushing’s Syndrome
Authors: Shibata Hirotaka , Suzuki Hiromichi , Maruyama Tatsuya , Saruta Takao
Published: June 2012

Abstract
The relation between serum cortisol, plasma renin activity, angiotensin II (Ang II), or aldosterone levels and peripheral blood cell (mononuclear leukocytes and platelets) angiotensin II type 1A (AT
1A
) and 1B (AT
1B
) receptor mRNA levels was examined in both patients with Cushing’s syndrome (seven patients with Cushing’s syndrome due to unilateral adrenal cortical adenoma) and control subjects (seven normotensive patients with renal cell carcinoma). Blood was collected from each participant for estimation of plasma renin activity and plasma angiotensin II, aldosterone, and cortisol concentrations and for isolation of mononuclear leukocytes and platelets, which were then used to measure AT
1A
and AT
1B
receptor mRNA levels before and after adrenalectomy with the use of reverse transcription–polymerase chain reaction. In patients with Cushing’s syndrome, both mononuclear leukocyte and platelet AT
1A
mRNA levels, which were elevated, were reduced after removal of the adrenal tumors, whereas AT
1B
receptor mRNA levels of both types of blood cells did not significantly change after adrenalectomy. In contrast, in control subjects, both AT
1A
and AT
1B
receptor mRNA levels did not significantly change after unilateral adrenalectomy and nephrectomy. In the adrenal tumors of patients with Cushing’s syndrome, gene expression of AT
1A
receptor was decreased compared with that from adrenals of control subjects. AT
1A
receptors of the platelets were shown to be upregulated in a manner similar to those of mononuclear leukocytes in patients with Cushing’s syndrome. These results suggest that cortisol excess is an important factor upregulating AT
1A
receptor mRNA levels in human blood cells.
Role of the Rostral Ventrolateral Medulla in Maintenance of Blood Pressure in Rats With Goldblatt Hypertension
Authors: Bergamaschi Cassia , Campos Ruy R. , Schor Nestor , Lopes Oswaldo U.
Published: June 2012

Abstract
The aim of the present study was to examine the participation of the rostral ventrolateral medulla (RVLM) in the maintenance of hypertension in rats submitted to the renovascular Goldblatt (two-kidney, one clip) procedure. We inhibited or stimulated this area with the use of drugs such as glycine,
l
-glutamate, or kynurenic acid. (1) Bilateral microinjection of glycine (100 nmol, 200 nL, n=13) into the RVLM of hypertensive rats produced a decrease in mean arterial blood pressure (MAP) from 177.2±29.3 to 102.3±20.9 mm Hg (
P
<.05), which was similar to the decrease produced by intravenous administration of hexamethonium. The inhibition of RVLM with glycine in normotensive rats produced a decrease in MAP from 106±17.1 to 59.7±7.3 mm Hg (
P
<.05, n=9). (2) An impressive increase in MAP from 153.3±16.3 to 228±34.9 mm Hg (
P
<.05) occurred in hypertensive rats after microinjection of
l
-glutamate (50 nmol, 200 nL, n=6) into the RVLM. The same procedure caused a significant but less intense increase in MAP from 105±13.8 to 148.3±24.9 mm Hg in normotensive rats (
P
<.05, n=6). (3) A decrease in MAP from 151.6±25.3 to 96.8±22.5 mm Hg occurred in hypertensive rats after microinjection of the broad-spectrum glutamate antagonist kynurenic acid (4 nmol, 200 nL, n=6) into the RVLM, whereas the same procedure did not change MAP in normotensive animals (n=6). Heart rate was not significantly affected in any group. Together these results show that the activity of RVLM neurons is important in the maintenance of arterial blood pressure in Goldblatt hypertensive rats and probably indicate a change in the sensitivity and/or number of glutamatergic receptors in this area after the development of hypertension.
Pressor and Reflex Sensitivity Is Altered in Spontaneously Hypertensive Rats Treated With Angiotensin-(1-7)
Authors: Benter Ibrahim F. , Diz Debra I. , Ferrario Carlos M.
Published: June 2012

Abstract
We have suggested that angiotensin-(1-7) [Ang-(1-7)] may oppose the pressor activity of angiotensin II (Ang II). This hypothesis was supported by the fact that long-term intravenous infusion of Ang-(1-7) transiently lowers blood pressure in spontaneously hypertensive rats (SHR). We now investigated whether the pressor sensitivity to bolus injections of either phenylephrine (PE) or Ang II was altered on day 12 of an Ang-(1-7) infusion when blood pressure in the SHR had returned to hypertensive levels. SHR (n=10) and WKY rats (n=8) were given Ang-(1-7) intravenously via osmotic minipumps at a dose of 24 μg/kg per hour for 2 weeks. On day 12 of the infusion, mean arterial pressure and heart rate in halothane-anesthetized rats were similar in Ang-(1-7)–treated SHR (142±6 mm Hg; 388±9 beats per minute) and those infused with vehicle (146±5 mm Hg; 392±13 beats per minute). Pressor responsiveness to PE in Ang-(1-7)–treated SHR was 22% less at a dose of 10 μg, while pressor responses to Ang II decreased by 20% and 25% at doses of 0.05 and 0.1 μg, respectively, compared with the vehicle-treated SHR (
P
<.05). There were no effects of the Ang-(1-7) infusion on pressor responses to Ang II or PE in WKY rats. In the SHR infused with Ang-(1-7), there was a 35% improvement in sensitivity of the reflex control of heart rate to levels not different from those in the untreated WKY rats (slope of the change in pulse interval versus the change in pressure increased from 0.34±0.03 to 0.46±0.01 ms/mm Hg). These data suggest that Ang-(1-7) may selectively activate antihypertensive mechanisms at the level of the vascular wall or the baroreflex.
Inhibition of Atrial Natriuretic Peptide Excretory Action by Bradykinin
Authors: Boric Mauricio P. , Croxatto Héctor R.
Published: June 2012

Abstract
We examined whether the excretory effect of atrial natriuretic peptide could be antagonized by intravenously administered bradykinin or by elevated endogenous kinin levels attained during converting enzyme inhibition. Urinary volume and sodium and potassium excretion were determined every 20 minutes in female, anesthetized Sprague-Dawley rats (weight, 0.19 to 0.22 kg) infused with 10 μL/min isotonic glucose. In some experiments, urinary cGMP content was measured by radioimmunoassay. Two intravenous boluses of 209 pmol (0.5 μg) atrial natriuretic peptide were given before and after the injection of test substances, and the response ratio was used to quantify inhibition. Single injections of 94.3 or 142 pmol (100 or 150 ng) bradykinin, 3 minutes prior to atrial natriuretic peptide, inhibited the excretion of water, sodium, and potassium by 70%, 75%, and 50%, respectively. Larger (236 to 472 pmol) or smaller (23.6 to 47.2 pmol) bradykinin doses were ineffective. None of the bradykinin doses tested affected basal urinary output, systemic pressure, or the modest depressor effect of atrial natriuretic peptide. The anti–atrial natriuretic peptide effect of bradykinin was completely prevented by the kinin receptor antagonist Hoe 140. Converting enzyme inhibition with ramipril (96 nmol IV) also blunted atrial natriuretic peptide diuresis and natriuresis by 70% and reduced urinary cGMP excretion by 50%. These effects of ramipril were mediated by endogenous kinin accumulation, since they were abolished by pretreatment with Hoe 140. It is concluded that intrarenal kinins modulate the renal actions of atrial natriuretic peptide, and at a precise concentration bradykinin strongly antagonizes atrial natriuretic peptide by preventing its transduction mechanism.
Regulation of Neuronal Calcitonin Gene–Related Peptide Expression
Authors: Supowit Scott C. , Zhao Huawei , Wang Donna H. , DiPette Donald J.
Published: June 2012

Abstract
Calcitonin gene–related peptide (CGRP) is a potent vasodilator neuropeptide. We have previously demonstrated that CGRP mRNA levels are increased in dorsal root ganglia, and immunoreactive CGRP content is elevated in the spinal cord in mineralocorticoid-salt hypertension. Dorsal root ganglia neuronal cell bodies synthesize CGRP and send axons peripherally to blood vessels and centrally to spinal cord sites involved in blood pressure regulation. This increased synthesis of a potent vasodilator is a compensatory response to attenuate the increase in blood pressure; however, it is not known if neuronal CGRP is regulated simply by the elevated blood pressure or by changes in other parameters. To determine if elevation of blood pressure in normal rats induced by the administration of a potent vasoconstrictor can increase neuronal CGRP mRNA, 7-week-old male Sprague-Dawley rats were treated for 2 weeks with either angiotensin II (n=6) or vehicle (n=6) by using implanted osmotic minipumps. After the treatment period, the angiotensin II–treated rats displayed a marked increase in systolic blood pressure (angiotensin II, 217±18 versus control, 131±3 mm Hg,
P
<.001), and decrease in plasma renin activity (angiotensin II, 3.7±3.5 versus control, 35.9±14.2 ng · mL
−1
· h
−1
,
P
<.05). However, dorsal root ganglia CGRP mRNA content did not significantly differ between the two groups of rats. These results demonstrate that a marked increase in blood pressure, by itself, does not increase neuronal CGRP mRNA accumulation. We propose that in mineralocorticoid-salt hypertension there are specific changes in as yet unidentified factor(s) that modulate neuronal synthesis and release of CGRP independent of blood pressure elevation.
Effects of an Endothelin Receptor Antagonist in Rats With Cyclosporine-Induced Hypertension
Authors: Takeda Yoshiyu , Miyamori Isamu , Wu Piengsheng , Yoneda Takashi , Furukawa Kenji , Takeda Ryoyu
Published: June 2012

Abstract
Cyclosporine, a potent immunosuppressant, is associated with the development of hypertension and nephrotoxicity. We have previously shown that endothelin release from the arteries is increased in rats with cyclosporine-induced hypertension. We conducted the present study to determine whether the specific endothelin type A (ET
A
) receptor antagonist FR 139317 prevents cyclosporine-induced hypertension and whether cyclosporine increases ET
A
receptor mRNA in blood vessels. Cyclosporine (25 mg/kg per day) given for 4 weeks increased blood pressure from 98±12 to 156±14 mm Hg; this increase was blunted by coadministration of 10 mg/kg per day FR 139317 (ie, blood pressure was 138±14 mm Hg) in Wistar-Kyoto rats. Cyclosporine induced greater vasoconstrictor responses to norepinephrine and angiotensin II in isolated mesenteric arteries. FR 139317 normalized the vasoconstrictor responses to angiotensin II and norepinephrine. Cyclosporine (25 mg/kg per day) given for 4 weeks increased ET
A
receptor mRNA expression in the rat aorta and mesenteric artery (170% and 176%, respectively). Little change was observed in ET
B
receptor mRNA. These results indicate that cyclosporine may increase blood pressure by increasing not only endothelin production but also ET
A
receptor in the vasculature. The specific ET
A
receptor antagonist FR 139317 may prevent the hypertension induced by cyclosporine.
Radial Artery Compliance in Young, Obese, Normotensive Subjects
Authors: Mangoni Arduino A. , Giannattasio Cristina , Brunani Amelia , Failla Monica , Colombo Manuela , Bolla Giovanbattista , Cavagnini Francesco , Grassi Guido , Mancia Giuseppe
Published: June 2012

Abstract
Obesity is characterized by a number of cardiovascular alterations, and whether these alterations involve arterial compliance is unknown. In 12 young, obese, normotensive subjects (age, 23.9±1.3 years; mean±SEM) and 12 age- and sex-matched lean control subjects we measured blood pressure, radial artery diameter, and radial artery compliance continuously over the systodiastolic pressure range with a Finapres device and recently developed echo-tracking device. Measurements were obtained at baseline and after prolonged ischemia, that is, when diameter and compliance are increased. Blood pressure values were normal in both groups (obese subjects: 109.2±4.9/68.2±2.7 mm Hg; lean control subjects: 108.2±4.1/60.7±3.8 mm Hg), but in addition to a marked increase in body mass index (38.5±0.8 versus 23.1±0.9 kg/m
2
,
P
<.01), obese subjects showed a slight and nonsignificant increase in heart rate (71.1±3.2 versus 66.7±3.3 beats per minute,
P
=NS), increases in left ventricular wall thickness and left ventricular mass index (121.5±4.8 versus 103.4±3.3 kg/m
2
,
P
<.01), no changes in plasma renin activity and plasma norepinephrine (compared with normal values), and a marked reduction in total body glucose uptake (glucose clamp technique). Obese subjects showed radial artery diameter and compliance values that were greater than those seen in control subjects throughout the systodiastolic pressure range. The differences were 13% (
P
<.05) and 96% (
P
<.01), respectively, and both diameter and compliance remained higher in obese than lean subjects after forearm ischemia. In obese and lean subjects baseline radial artery diameter values correlated highly with body weight, body surface area, and body mass index. Thus, radial artery compliance is increased in young, obese, normotensive subjects. Whether these changes are related to functional factors or intravascular or extravascular structural changes remains to be determined. The increase, however, is similar to what has been described in mild essential hypertension, emphasizing the similarity of the cardiovascular alterations in these two conditions.
A Survey of Blood Pressure Distribution in Pygmy and Bantu Populations in Cameroon
Authors: Kesteloot Hugo , Ndam Ndjitoyap , Sasaki Satoshi , Kowo Mathurin , Seghers Victor
Published: June 2012

Abstract
A blood pressure survey was performed in isolated Pygmy communities and Bantu population samples living either in close relationship with the Pygmies or in separate areas within the same region. The Pygmies are still living as hunter-gatherers, whereas the Bantus rely on agriculture for food provision. Mean blood pressures in Pygmies were 130/85 mm Hg in males and 126/80 mm Hg in females and in Bantus were 137/87 mm Hg in males and 136/84 mm Hg in females. In spot urine the mean urinary sodium concentration was higher in Bantus than Pygmies (86 versus 37 mmol/L in males; 95 versus 56 mmol/L in females). In the total population urinary potassium concentration was very high (150 mmol/L), calcium concentration very low (0.4 mmol/L), and urea concentration low (6.9 g/L). After adjustment for age, height, weight, and sex, no racial differences in blood pressure were present. Blood pressure increased with age but body mass index did not. Diastolic pressure correlated significantly but negatively with urinary sodium in multiple regression analysis. Our study demonstrates that blood pressure increases with age in hunter-gatherer populations on a low to moderately high sodium diet in the presence of a low urinary excretion of calcium coupled with a low protein intake.
Effects of Cilazapril on Vascular Structure and Function in Essential Hypertension
Authors: Kiowski Wolfgang , Linder Lilly , Nuesch Reto , Martina Benedikt
Published: June 2012

Abstract
Hypertension is associated with an altered design of resistance vessels and decreased endothelium-dependent vasodilator response to acetylcholine. A role of angiotensin II in both defects is suggested by animal experiments in which angiotensin-converting enzyme inhibition reverted structural and functional changes. We investigated the effects of 20 weeks of therapy with the angiotensin-converting enzyme inhibitor cilazapril (5 mg twice daily) on the endothelium-dependent response to brachial artery infusions of acetylcholine and the endothelium-independent vascular relaxation after sodium nitroprusside in 22 subjects with mild to moderate essential hypertension. In addition, we measured minimal forearm vascular resistance (ratio of mean arterial pressure and forearm blood flow after heating, ischemia, and ischemic exercise) as an indirect estimate of vascular structure. Cilazapril decreased blood pressure (151±14/99±7 mm Hg during placebo to 138±17/89±8 mm Hg after cilazapril treatment,
P
<.01) and baseline (42.2±12.6 to 37.1±10.6 U,
P
<.05) and minimal (3.0±1.1 to 2.4±0.7 U, 15.9±20.2%;
P
<.05) forearm vascular resistances. The change in minimal forearm vascular resistance was unrelated to age, duration of hypertension, or changes in blood pressure. Sodium nitroprusside increased forearm blood flow from 2.6±1.0 to 11.4±5.9 mL/min per 100 mL and acetylcholine to 21.5±17.8. Both responses did not change after cilazapril. The data provide indirect evidence that cilazapril therapy may improve vascular structure in human hypertension. The lack of relationship between vascular and blood pressure changes would be compatible with experimental evidence supporting a role for angiotensin II in the development and regression of vascular changes, but this needs further study. Therapy with cilazapril for 20 weeks, like other antihypertensive therapy, does not seem to influence endothelial vasodilator function in humans to a significant degree.
11α- and 11β-Hydroxyprogesterone, Potent Inhibitors of 11β-Hydroxysteroid Dehydrogenase, Possess Hypertensinogenic Activity in the Rat
Authors: Souness Graham W. , Morris David J.
Published: June 2012

Abstract
The progesterone derivatives 11α- and 11β-hydroxyprogesterone are potent inhibitors of 11β-hydroxysteroid dehydrogenase (isoforms 1 and 2) in vitro and can confer mineralocorticoid activity on corticosterone in the rat in vivo. 11β-Hydroxysteroid dehydrogenase metabolizes active glucocorticoids to their inactive 11-dehydro products and protects renal mineralocorticoid receptors from the high circulating levels of endogenous glucocorticoids. 11β-Hydroxysteroid dehydrogenase has been suggested to be important not only in the control of renal sodium retention but also of blood pressure. To assess the possible blood pressure–modulating effects of 11α- and 11β-hydroxyprogesterone, we infused these substances into both intact and adrenalectomized Sprague-Dawley rats continuously for 14 days. Both 11α- and 11β-hydroxyprogesterone caused a significant elevation in blood pressure within 3 days, an effect that persisted throughout the 14-day infusion. The hypertensive effects of 11α-hydroxyprogesterone were abolished by adrenalectomy and significantly attenuated when 11α-hydroxyprogesterone was infused together with the specific mineralocorticoid receptor antagonist RU28318. In an additional series of experiments, 11α-hydroxyprogesterone significantly amplified the hypertensive effects of corticosterone in adrenalectomized spontaneously hypertensive rats but had no effects by itself in this experimental animal. These results demonstrate that both 11α- and 11β-hydroxyprogesterone are potently hypertensinogenic in the rat and that this activity depends on an intact adrenal and at least in part on the activation of mineralocorticoid receptors. 11β-Hydroxyprogesterone, and similar endogenous progesterone metabolites that inhibit 11β-hydroxysteroid dehydrogenase, may be involved in the pathology of certain hypertensive states.