bluuebunny/crossref_metadata_2025 huggingface dataset:
Fish oil amplifies the effect of propranolol in mild essential hypertension.
Authors: Singer P , Melzer S , Goschel M , Augustin S
Published: June 2012

Forty-seven male patients with mild essential hypertension were randomly allocated to three subgroups. After a run-in period of 4 weeks, the first subgroup (n = 16) received propranolol (80 mg/day) for 36 weeks followed by a placebo period of 4 weeks. The second subgroup (n = 15), after a run-in period of 4 weeks, was given a supplement of encapsulated fish oil (9 g/day) for 36 weeks with a subsequent period of 4 weeks in which fish oil placebo was given. The third subgroup (n = 16), after a run-in period of 4 weeks, was given propranolol (80 mg/day) for 12 weeks, propranolol (80 mg/day) plus fish oil capsules (9 g/day equivalent to 1.8 g/day of eicosapentaenoic acid and 1.1 g/day of docosahexaenoic acid) for 12 weeks, propranolol plus fish oil placebo (same doses for 12 weeks) with a subsequent period of 4 weeks when propranolol placebo was administered. The results indicate a blood pressure-lowering effect of fish oil, which was comparable with that of propranolol. The simultaneous intake of fish oil plus propranolol was more effective than propranolol or fish oil alone. Propranolol treatment resulted in a decrease of plasma norepinephrine, plasma renin activity, and thromboxane B2 formation. After fish oil supplementation, plasma norepinephrine and thromboxane B2 formation were likewise reduced, whereas plasma renin activity appeared increased. The decrease of serum triglycerides, total and low density lipoprotein cholesterol as well as the rise of high density lipoprotein cholesterol are concomitant beneficial effects, which justify the consideration of fish oil alone or in combination with antihypertensive drugs for the treatment of mild hypertension.
Sympathetic neural adjustments to stress in physically trained and untrained humans.
Authors: Seals D R
Published: June 2012

The purpose of this study was to determine if the state of physical training influences sympathetic neural activation during acute stress in humans. We recorded muscle sympathetic nerve activity (microneurography of the peroneal nerve), arterial blood pressure, and heart rate in 12 highly trained, endurance athletes (25 +/- 1 years, mean +/- SEM) and 12 untrained subjects (27 +/- 1 years) before (supine rest control) and during: 1) lower body negative pressure at -5, -10, -15, and -20 mm Hg (orthostatic stress); 2) isometric handgrip at 30% of maximum (exercise stress); and 3) hand immersion in ice water, that is, the cold pressor test (thermal stress). Body weight was not different in the two groups, but the athletes had a lower body fat content (8.9 +/- 1.3% versus 16.1 +/- 2.0%, p less than 0.05). During supine rest, muscle sympathetic nerve burst frequency (24 +/- 3 versus 24 +/- 2 bursts/min, athletes versus untrained subjects) and burst incidence (36 +/- 3 versus 44 +/- 4 bursts/100 heart beats) and arterial blood pressure were not different in the two groups, but heart rate was lower in the athletes (54 +/- 2 versus 67 +/- 3 beats/min, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Prevention of hypertension and vascular changes by captopril treatment.
Authors: Lee R M , Berecek K H , Tsoporis J , McKenzie R , Triggle C R
Published: June 2012

Treatment of female spontaneously hypertensive rats (SHR) and control Wistar-Kyoto (WKY) rats with captopril was carried out by the addition of the drug in the drinking water throughout pregnancy and lactation and after weaning. At 28 weeks of age, average systolic blood pressure of treated SHR was 113 +/- 3 mm Hg, which was below that of control SHR (188 +/- 3 mm Hg) and WKY rats (124 +/- 3 mm Hg). Body weight and heart rate of the SHR were not affected by the treatment. Tissue level of catecholamines was increased by captopril treatment in the superior cervical ganglia but remained unchanged in the plasma, heart, mesenteric arteries, and the adrenal glands of both SHR and WKY rats. Left ventricular weight, wall thickness, and internal diameter of the left ventricle in the SHR were reduced by the treatment. Morphometric measurements of the mesenteric arteries showed that vascular alterations present in the control SHR were prevented by the treatment. In the superior mesenteric artery and large mesenteric artery, smaller lumen size at maximal relaxation found in the control SHR was normalized to the level of the WKY rats. Hypertrophy of the medial wall in the superior mesenteric, large and small mesenteric arteries, and an increase in the number of smooth muscle cell layers in the large mesenteric artery of the SHR were prevented by the treatment. Perfusion study of the mesenteric vascular bed showed that reactivity of these vessels to norepinephrine was reduced, and sensitivity to norepinephrine (as determined by the effective dose that causes 50% of maximal response) was increased in the SHR by captopril treatment. Sensitivity of the tail artery in response to norepinephrine was not altered by the treatment. We conclude that long-term treatment with captopril of SHR before and after birth prevented the development of hypertension, structural and functional alterations of the mesenteric arteries, and cardiac hypertrophy.
Cosegregation of blood pressure with a kallikrein gene family polymorphism.
Authors: Pravenec M , Kren V , Kunes J , Scicli A G , Carretero O A , Simonet L , Kurtz T W
Published: June 2012

It has recently been proposed that sequence variation in the gene coding for tissue kallikrein might be involved in the pathogenesis of hypertension. However, molecular evidence of an association between a sequence alteration in the kallikrein gene family and the transmission of increased blood pressure has never been reported. In 32 recombinant inbred (RI) strains derived from the spontaneously hypertensive rat (SHR) and the normotensive Brown Norway rat (BN), we investigated whether a restriction fragment length polymorphism (RFLP) marking the kallikrein gene family cosegregated with blood pressure. In the RI strains that inherited the kallikrein RFLP from the SHR progenitor strain, the median systolic, diastolic, and mean arterial pressures were significantly greater than in the RI strains that inherited the kallikrein RFLP from the BN progenitor strain. These findings suggest that in the rat, sequence variation in the kallikrein gene family, or in closely linked genes, may have the capacity to affect blood pressure.
Adrenergic stimulation of renal prostanoids in the Lyon hypertensive rat.
Authors: Liu K L , Aissa A H , Laréal M C , Benzoni D , Vincent M , Sassard J
Published: June 2012

Young, genetically hypertensive Lyon (LH) rats exhibited an increased renal in vivo turnover of norepinephrine and an elevated urinary excretion of thromboxane B2 when compared with normotensive (LN) and low blood pressure (LL) controls. Therefore, the effects of norepinephrine (1.2 x 10(-8) to 9.6 x 10(-7) M) and of phenylephrine (5 x 10(-8) to 1.9 x 10(-6) M) on renal function and the urinary excretion of prostanoids were assessed in isolated perfused kidneys of 8-week-old LH, LN, and LL rats. In addition, the effects of norepinephrine were assessed before and during thromboxane A2/prostaglandin H2 receptor blockade by AH23848 (4 x 10(-6) M). Before drug infusion, LH kidneys differed from those of LN and LL controls by having an elevated renal vascular resistance and a decreased natriuresis and glomerular filtration rate; the urinary output of prostaglandin E2 and F2 alpha, of 6-ketoprostaglandin F1 alpha, and of thromboxane B2 was similar in the three strains. The constrictor effects of norepinephrine and phenylephrine were significantly increased in LH rat kidneys compared with LL but not with LN controls, and their pressure-natriuresis was markedly reduced. Norepinephrine and phenylephrine induced a 10- to 20-fold dose-dependent increase in the synthesis of the four prostanoids, which was more pronounced in LH than in LN and LL rats for thromboxane B2 only. AH23848 infusion significantly reduced the vascular effects of norepinephrine and increased the natriuretic response of LH but not of LN and LL rat kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
Kinetic abnormalities of the red blood cell sodium-proton exchange in hypertensive patients.
Authors: Canessa M , Morgan K , Goldszer R , Moore T J , Spalvins A
Published: June 2012

The present study was designed to examine the kinetics of Na(+)-H+ exchange in red blood cells of normotensive and hypertensive subjects and its relation to the previously reported abnormalities in Na(+)-Li+ exchange. The Na(+)-H+ antiporter activation kinetics were studied by varying cell pH and measuring net Na+ influx (mmol/l cell x hr = units) driven by an outward H+ gradient. The Na(+)-Li+ exchange was determined at pH 7.4 as sodium-stimulated Li+ efflux. Untreated hypertensive patients (n = 30) had a higher maximal rate of Na(+)-Li+ exchange (0.43 +/- 0.05 versus 0.26 +/- 0.02 units, p less than 0.0003), a higher maximal rate of Na(+)-H+ exchange (62.3 +/- 6.2 versus 47 +/- 4 units; p less than 0.02), but a similar affinity for cell pH compared with normotensive subjects (n = 46). The cell pH activation of the Na(+)-H+ antiporter exhibited a lower Hill coefficient than that of normotensive subjects (1.61 +/- 0.12 versus 2.56 +/- 0.14; p less than 0.0001). This index of occupancy of internal H+ regulatory sites was found reduced in most of the hypertensive patients (73%) whether their hypertension was untreated or treated. Hypertensive patients with Na(+)-Li+ exchange above 0.35 units (0.68 +/- 0.057 units, n = 16) did not exhibit elevated maximal rates of Na(+)-H+ exchange (57.3 +/- 10 units, NS) in comparison with those with Na(+)-Li+ exchange below 0.35 units (66.4 +/- 7.6 units, n = 26), but both groups exhibited reduced Hill coefficients. Hypertensive patients with enhanced Na(+)-H+ exchange activity (more than 90 units) had normal maximal rates of Na(+)-Li+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of age on coronary circulation after imposition of pressure-overload in rats.
Authors: Isoyama S , Sato F , Takishima T
Published: June 2012

We examined the effects of pressure overload on coronary circulation in young adult (7 months old) and old rats (18 months old). Four weeks after the ascending aorta was banded, in vivo left ventricular pressure was measured to estimate the degree of pressure load. In the two age groups, similar increases in peak left ventricular pressure were observed (113 +/- 7 mm Hg in sham-operated rats versus 160 +/- 11 mm Hg in banded rats of the young adult group; 103 +/- 7 mm Hg in sham-operated rats versus 156 +/- 11 mm Hg in banded rats of the old group). After isolating the hearts, they were perfused with Tyrode's solution containing bovine red blood cells and albumin. Resting coronary perfusion pressure-flow relations and reactive hyperemic response after a 40-second ischemia were obtained under beating but nonworking conditions. In young adult banded rats, significant myocardial hypertrophy was observed at the organ level (124% of controls in left ventricular dry weight/body weight ratio; 119% in left ventricular dry weight/tibial length ratio) and at the cell level. Minimal coronary vascular resistance obtained by the perfusion pressure-peak flow relation during reactive hyperemia increased to 150% of controls, and coronary flow reserve decreased significantly. In contrast, myocardial hypertrophy was not observed at the organ or cell level in old banded rats. However, minimal coronary vascular resistance increased, and flow reserve decreased significantly. Thus, pressure overload with coronary arterial hypertension caused abnormalities of the coronary circulation in old subjects even in the absence of myocardial hypertrophy.
Human prorenin.
Authors: Hsueh W A , Baxter J D
Published: June 2012

Human prorenin is the enzymatically inactive biosynthetic precursor of renin. Recent interest has focused on the posttranslational sorting and processing of prorenin to renin since markedly increased levels of circulating prorenin have been associated with both physiological and pathological changes. These observations raise the question of whether prorenin processing may be a regulatory event in renin production in the kidney. In the juxtaglomerular cells of the kidney, prorenin can be sorted to either of two pathways: 1) the regulated pathway, which is mediated by secretory granules, where a thiol protease resembling cathepsin B processes prorenin to renin by cleavage of the amino terminal 43-amino acid prosegment, which allows exposure of the active site of renin, or 2) the constitutive pathway, which is not regulated and does not involve conversion of prorenin to renin. Studies in which segments of prorenin are modified by site-directed mutagenesis suggest that the prosegment and glycosylation are not required for sorting, although they may influence or participate in sorting, or both. Certain areas in the prosegment are important determinants of enzyme activity and ability to cleave the prosegment. Further structural analysis of prorenin will be useful to assess details of its sorting and processing. In addition, a number of extrarenal tissues such as uterine lining, ovarian theca, corpus luteum, pituitary, and adrenal, express the renin gene. These tissues have different capabilities to sort and process prorenin compared with kidney, and some tissues secrete only prorenin. Whether prorenin-to-renin conversion is necessary to activate these local renin-angiotensin systems is a key issue.(ABSTRACT TRUNCATED AT 250 WORDS)
Once-daily fosinopril in the treatment of hypertension.
Authors: Anderson R J , Duchin K L , Gore R D , Herman T S , Michaels R S , Nichola P S , Nolen T M , Wolfson P , Wombolt D G , Zusman R
Published: June 2012

This multicenter, dose-ranging study evaluated the antihypertensive effectiveness of once-daily administration of fosinopril sodium in 220 patients with supine diastolic blood pressure of 95-115 mm Hg. After a 4-week placebo period, patients were randomly assigned to double-blind therapy with either placebo or 10, 40, or 80 mg fosinopril once daily for 4 weeks. If treatment goals were not met, chlorthalidone 25 mg/day was added for weeks 5 to 8. Thereafter, patients could enter the long-term, open-label phase and receive 10-80 mg/day fosinopril plus chlorthalidone, if needed. After 4 weeks of monotherapy, the average decreases in supine diastolic blood pressure were 9% (10 mg), 11.5% (40 mg), and 12.5% (80 mg) compared with 6% in the placebo group. After 8 weeks, the average decreases, with or without diuretic therapy, were 12.5-18.2%, compared with 10.8% with placebo. Blood pressure continued to be well controlled, and the patients showed no evidence of tachyphylaxis or tolerance through 12-15 months of treatment. Fosinopril was well tolerated. During the short-term phase, no patient withdrew because of adverse events possibly related to fosinopril; during the long-term phase, nine of 148 patients (6.1%) withdrew for that reason. In patients with mild-to-moderate hypertension, once-daily fosinopril (40 and 80 mg) provided significant antihypertensive effects with or without diuretic therapy. The 10 mg dose was effective in some patients and may be considered a starting dose.
Central hemodynamic observations in untreated preeclamptic patients.
Authors: Visser W , Wallenburg H C
Published: June 2012

Reported central hemodynamics obtained with a Swan-Ganz pulmonary artery thermodilution catheter in preeclamptic patients show marked disparity, which has been interpreted to indicate a variable hemodynamic expression of the disease. However, the variability also may be due, at least in part, to the pharmacological treatment that most of the women studied received during Swan-Ganz measurements. To evaluate the effects of treatment on hemodynamics, we compared the results of Swan-Ganz measurements in 87 preeclamptic women who had received no treatment at all with those obtained in 47 preeclamptic women who had received various drugs and intravenous fluids. Control values were obtained in 10 normotensive pregnant volunteers. Measurements were performed between 25 and 34 weeks of gestation. The median (range) cardiac index in the untreated patients of 3.3 (2.0-5.3) l.min-1.m-2 was significantly lower than that in the treated patients of 4.3 (2.4-7.6) l.min-1.m-2 and in the normotensive pregnant women of 4.2 (3.5-4.6) l.min-1.m-2. The systemic vascular resistance index in the untreated group of 3,003 (1,771-5,225) dyne.sec.cm-5.m2 was significantly higher than that of 2,212 (1,057-3,688) in the treated and of 1,560 (1,430-2,019) dyne.sec.cm-5.m2 in the normotensive control group. The median (range) pulmonary capillary wedge pressure in the untreated group was 7 (-1-20) mm Hg and did not differ from that of 7 (0-25) mm Hg in the treated group. Variability of all hemodynamic variables was much lower in untreated than in treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Contribution of regional vascular responses to whole body autoregulation in conscious areflexic rats.
Authors: Hinojosa-Laborde C , Frohlich B H , Cowley A W
Published: June 2012

We designed studies to evaluate the autoregulation response during volume expansion in three major circulation regions (intestine, kidney, and hind limb) during simultaneous determination of whole body autoregulation in conscious areflexic rats. Cardiac output was measured with chronically implanted electromagnetic flow probes on the ascending aorta. Regional blood flow velocity was measured with pulsed Doppler flow probes on the superior mesenteric (n = 7), left renal (n = 7), and right iliac (n = 7) arteries. Doppler flow probes were calibrated in situ in each rat to determine regional blood flow values. Neurohumoral reflex control of pressure was removed pharmacologically, and blood pressure and cardiac output were returned to resting control values with intravenous norepinephrine infusion, which was maintained at that constant level throughout the study. Hemodynamic changes were measured in response to blood volume expansion with infusion of 0.9 ml blood over 6 minutes. This small change in blood volume resulted in significant increases in vascular resistance of 15% in the whole body, 8% in the intestine, 18% in the kidney, and 15% in the hind limb. The pressure-flow slope, used as an index of autoregulation (slope = 0, perfect autoregulation; slope = 1, rigid vasculature), averaged 0.34 in the whole body, 0.52 in the intestine, 0.19 in the kidney, and 0.39 in the hind limb. When compared with the whole body, blood flow autoregulation was less in the intestine, greater in the kidney, and the same in the hind limb.
Identification and regulation of angiotensin II receptor subtypes on NG108-15 cells.
Authors: Tallant E A , Diz D I , Khosla M C , Ferrario C M
Published: June 2012

NG108-15 cells, a neurally derived clonal cell line, express various components of the renin-angiotensin system and thus serve as a model of the cellular action of angiotensin (Ang) II. NG108-15 cells contain a high-affinity binding site for Ang II, with a Kd of 1.1 nM and a Bmax of 6.5 fmol/mg protein. Ang peptides competed for 125I-Ang II binding with an order of potency of Ang II greater than Ang-(2-8) much greater than Ang-(1-7). The subtype 1 (or B)-selective Ang II receptor antagonist DuP 753 as well as [Sar1,Ile8]Ang II and [Sar1,Thr8]Ang II competed for Ang II binding with high affinity, whereas the subtype 2 (or A)-selective Ang receptor antagonist CGP 42112A was partially effective only at a 300-fold higher concentration. When NG108-15 cells were induced to differentiate by treatment with dibutyryl cyclic adenosine 3',5'-monophosphate, the density of Ang II receptors increased dramatically, with little change in affinity (1.1 versus 4.2 nM) or competition by Ang peptides. In marked contrast to undifferentiated cells, CGP 42112A became a potent competitor (IC50, 1 nM) for the majority (90-95%) of Ang II binding, whereas DuP 753 competed for only 5-10% of the binding sites. Ang II caused a dose-dependent mobilization of cytosolic Ca2+ in undifferentiated NG108-15 cells through activation of phospholipase C and the production of inositol 1,4,5-trisphosphate. In these cells, Ca2+ mobilization was blocked by either DuP 753 or the sarcosine Ang II analogues, whereas CGP 42112A was ineffective. Ang II also mobilized intracellular Ca2+ in differentiated NG108-15 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Expression of brain natriuretic peptide gene in human heart. Production in the ventricle.
Authors: Hosoda K , Nakao K , Mukoyama M , Saito Y , Jougasaki M , Shirakami G , Suga S , Ogawa Y , Yasue H , Imura H
Published: June 2012

To elucidate the expression of the brain natriuretic peptide gene in the human heart, we have measured brain natriuretic peptide mRNA levels in hearts using the Northern blot hybridization method. Brain natriuretic peptide mRNA was present with a size of approximately 0.9 kb in the ventricle as well as in the atrium. The brain natriuretic peptide mRNA level in the ventricle was 52% of that in the atrium, whereas the atrial natriuretic peptide mRNA level in the ventricle was approximately two orders of magnitude lower than that in the atrium. Taking atrial and ventricular weights into account, the total amount of brain natriuretic peptide mRNA in the ventricle represented 77% of that in the whole heart. These results demonstrate that most of brain natriuretic peptide mRNA occurs in the ventricle, in contrast with atrial natriuretic peptide mRNA, which is present mainly in the atrium, indicating that the ventricle is a major production site of brain natriuretic peptide.
Nucleus prepositus hypoglossi. A medullary pressor region.
Authors: Talman W T , Robertson S C
Published: June 2012

Electrical stimulation of fibers of passage through the fastigial nucleus increases arterial pressure. To identify nuclei that may project through the pressor region of the fastigial nucleus, we injected the retrograde tracer fast blue unilaterally at confirmed pressor sites in the nucleus. In seven rats, we found dense fluorescent labeling bilaterally in the external cuneate, lateral reticular, medial vestibular, and caudal prepositus hypoglossi nuclei, and contralaterally in the inferior olivary nucleus. There had been no reports of a cardiovascular role for the nucleus prepositus hypoglossi; thus, we sought to determine if electrical or chemical stimulation of that nucleus or the adjacent medial vestibular nucleus altered arterial pressure or heart rate in 24 anesthetized rats. Both types of stimuli to the caudal, but not the rostral, pole of the nucleus prepositus hypoglossi or to the medial vestibular nucleus elicited an increase in arterial pressure; bradycardia accompanied the former and tachycardia the latter. Both the nucleus prepositus hypoglossi and medial vestibular nucleus may participate in central cardiovascular regulation.
Vascular smooth muscle contractile elements. Cellular regulation.
Authors: Stull J T , Gallagher P J , Herring B P , Kamm K E
Published: June 2012

For many years the simple view was held that contractile force in smooth muscle was proportional to cytosolic Ca2+ concentrations ([Ca2+]i). With the discovery that phosphorylation of myosin light chain by Ca2+/calmodulin-dependent myosin light chain kinase initiated contraction, regulation of the contractile elements developed more complex properties. Molecular and biochemical investigations have identified important domains of myosin light chain kinase: light chain binding sites, catalytic core, pseudosubstrate prototope, and calmodulin-binding domain. New protein phosphatase inhibitors such as okadaic acid and calyculin A should help in the identification of the physiologically important phosphatase and potential modes of regulation. The proposal of an attached, dephosphorylated myosin cross bridge (latch bridge) that can maintain force has evoked considerable controversy about the detailed functions of the myosin phosphorylation system. The latch bridge has been defined by a model based on physiological properties but has not been identified biochemically. Thin-filament proteins have been proposed as secondary sites of regulation of contractile elements, but additional studies are needed to establish physiological roles. Changes in the Ca2+ sensitivity of smooth muscle contractile elements with different modes of cellular stimulation may be related to inactivation of myosin light chain kinase or activation of protein phosphatase activities. Thus, contractile elements in smooth muscle cells are not dependent solely on [Ca2+]i but use additional regulatory mechanisms. The immediate challenge is to define their relative importance and to describe molecular-biochemical properties that provide insights into proposed physiological functions.
Regulation of cerebral blood vessels by humoral and endothelium-dependent mechanisms. Update on humoral regulation of vascular tone.
Authors: Faraci F M , Heistad D D
Published: June 2012

Recent studies suggest that humoral and endothelium-dependent mechanisms may play an important role in the cerebral circulation. Angiotensin may acutely and chronically increase resistance of large cerebral arteries and reduce cerebral microvascular pressure without changing cerebral blood flow. We hypothesize that the brain may sense reductions in microvascular pressure and initiate compensatory neurohumoral responses to raise arterial pressure. Vasopressin appears to play an important role in regulation of production of cerebrospinal fluid and brain fluid volume. Vasopressin also may be protective when intracranial pressure is elevated. Endothelium-dependent mechanisms also may have important influences on tone of cerebral vessels. Synthesis of the endothelium-derived relaxing factor nitric oxide, or a nitric oxide-containing compound, appears to influence both basal tone and responses of large cerebral arteries to acetylcholine in vivo. Large cerebral arteries dilate in response to increased blood flow in vivo, and this response may be mediated in part by release of a humoral factor by endothelium. Endothelium-dependent responses of cerebral arterioles to receptor- and nonreceptor-mediated agonists are impaired during chronic hypertension. The mechanism of impairment of endothelium-dependent responses of cerebral arterioles appears to involve production of an endothelium-derived contracting factor.
Effects of an endogenous ouabainlike compound on heart and aorta.
Authors: Bova S , Blaustein M P , Ludens J H , Harris D W , DuCharme D W , Hamlyn J M
Published: June 2012

An endogenous ouabainlike compound (OLC) has been purified from human plasma, and mass spectrometry has shown it to be indistinguishable from plant-derived ouabain. This human OLC was tested for its effects on evoked tension in guinea pig left atria and aortic rings. The tissues were incubated at 37 degrees C in bicarbonate-buffered physiological salt solution gassed with 95% O2-5% CO2. In atria stimulated electrically at 1 Hz, 85 and 170 nM human OLC increased peak active force to 177 +/- 15% and 313 +/- 32% of control, respectively (n = 3), with little effect on the duration of contraction. On washout of the OLC, peak systolic force returned to the control level with a half-time of 4.3 +/- 0.5 minutes. Similar results were obtained with 160 nM plant-derived ouabain: peak systolic force increased to 310 +/- 31% of control (n = 4) and returned to the control level with a half-time of 3.8 +/- 0.2 minutes during washout. In aortic rings, neither 170 nM human OLC nor 160 nM plant ouabain (30-minute treatments) affected resting (unstimulated) tension, but they increased the contractions evoked by histamine (0.2-1.0 microM) to 156 +/- 13% (n = 4) and 143 +/- 6% (n = 4) of control responses, respectively. The mean half-time for washout of the OLC and plant ouabain-induced augmentation of histamine-evoked tension exceeded 35 minutes. These data show that human OLC has cardiotonic and vasotonic actions qualitatively and quantitatively similar to those observed with plant ouabain.(ABSTRACT TRUNCATED AT 250 WORDS)
Platelet-free calcium and vascular calcium uptake in ethanol-induced hypertensive rats.
Authors: Vasdev S , Sampson C A , Prabhakaran V M
Published: June 2012

This study examined the effect of moderate ethanol intake on systolic blood pressure, platelet cytosolic free calcium, aortic calcium, and rubidium-86 uptake in Wistar-Kyoto rats. Twelve Wistar-Kyoto rats, aged 6 weeks, were given 5% ethanol in drinking water the first week followed by 10% ethanol in drinking water for the next 6 weeks. Twelve control animals were given regular tap water. Systolic blood pressure in the ethanol-treated rats was significantly higher (p less than 0.05) than that in controls after 1 week and remained higher throughout the study. At 13 weeks of age, platelet cytosolic free calcium and calcium uptake by aortas were significantly higher (p less than 0.001) in ethanol-treated animals as compared with those in controls. Ethanol intake did not affect aortic ouabain-sensitive 86Rb uptake. The in vitro effect of ethanol on calcium-45 and 86Rb uptake was also investigated in aortas of untreated Wistar-Kyoto rats at 13 weeks of age. In vitro ethanol (2.5-20 mmols/l) did not significantly affect 45Ca and 86Rb uptake in rat aortas. The increases in systolic blood pressure, platelet cytosolic free calcium, and vascular calcium uptake suggest that increases in cytosolic free calcium and calcium uptake mechanisms are associated with ethanol-induced hypertension.
Genetic heterogeneity of the spontaneously hypertensive rat.
Authors: Nabika T , Nara Y , Ikeda K , Endo J , Yamori Y
Published: June 2012

We examined DNA fingerprints of the spontaneously hypertensive rat from Shimane Institute of Health Science, Izumo, Japan, including seven substrains that were separated in the early stages of the establishment of the stroke-prone spontaneously hypertensive rat, and compared their fingerprints with those of rats from other sources. Obtained DNA fingerprints revealed that, in both the stroke-resistant spontaneously hypertensive rat and the Wistar-Kyoto rat, there is a substantial genetic difference between the rats from the National Institutes of health and from Shimane Institute of Health Science. By contrast, only a small genetic difference was observed either between the rats from the National Institutes of Health and Charles River Laboratories or among the substrains of the spontaneously hypertensive rat in the Shimane Institute of Health Science. Further, in the strains from the Shimane Institute of Health Science, there were fingerprinting bands that could distinguish either the Wistar-Kyoto rat from all the substrains of the spontaneously hypertensive rat or the stroke-prone from the stroke-resistant spontaneously hypertensive rat in spite of their close genetic backgrounds. From the observations above, we concluded 1) that there is substantial genetic variance of the spontaneously hypertensive rat between the two major sources in the world, the National Institutes of Health and the Shimane Institute of Health Science and 2) that by DNA fingerprinting analysis, it is possible to identify the restriction fragment length polymorphisms that are specific for the spontaneously hypertensive rat or the stroke-prone spontaneously hypertensive rat. These polymorphisms can be applied in the segregation study of the F2 generation.
Human astrocytes contain two distinct angiotensin receptor subtypes.
Authors: Tallant E A , Jaiswal N , Diz D I , Ferrario C M
Published: June 2012

The ability of angiotensin peptides to stimulate prostaglandin release and raise intracellular calcium levels by activating a phosphoinositide-specific phospholipase C was assessed in three human astrocytoma cell lines (CRTG3, STTG1, and WITG2). The addition of angiotensin II to CRTG3 cells resulted in a dose-dependent release of prostaglandin E2 and prostacyclin, the production of inositol 1,4,5-trisphosphate, and the mobilization of intracellular calcium. Angiotensin-(1-7), previously considered to be an inactive metabolite of angiotensin II, was as potent as angiotensin II for prostaglandin release but did not activate phospholipase C or mobilize intracellular calcium. In contrast, angiotensin-(2-8) caused only a slight increase in prostaglandin release, even though it was as effective as angiotensin II in augmenting inositol 1,4,5-trisphosphate production and calcium mobilization. Moreover, neither the release of prostaglandins in response to angiotensin II or angiotensin-(1-7) nor the mobilization of intracellular calcium in response to angiotensin II required extracellular calcium. Angiotensin II and angiotensin-(1-7) caused the release of prostaglandins from all three human astrocytoma cell lines, but changes in the level of intracellular calcium in response to angiotensin II only occurred in CRTG3 cells. Although previous studies have provided evidence for angiotensin receptor subtypes on the basis of selectivity of antagonists or signal transduction mechanisms, these data suggest that human astrocytes contain multiple angiotensin receptor subtypes on the basis of their response to different angiotensin heptapeptides--angiotensin-(1-7) and angiotensin-(2-8).(ABSTRACT TRUNCATED AT 250 WORDS)
Attenuated vascular reactivity in dogs with anteroventral third ventricle lesions.
Authors: Brum J M , Tramposch A F , Block C H , Estafanous F G , Ferrario C M
Published: June 2012

Lesion of the anteroventral portion of the third cerebral ventricle causes hypernatremia, adipsia, and attenuation of the pressor response to intravenous administration of angiotensin II and norepinephrine. In addition, these lesions prevent the development of several experimental models of hypertension. In this study, a lesion of the third cerebral ventricle region was made in 14 dogs. In seven dogs in which hypernatremia developed the lesions included the organum vasculosum of the lamina terminalis; seven animals in which the circumventricular organ was spared by the lesion remained normonatremic. Vascular responsiveness of isolated right carotid artery rings to angiotensin II and phenylephrine was assessed 3 days after lesioning the anteroventral portion of the third cerebral ventricle. In endothelium-denuded ring vessels, vasoconstrictor responses to phenylephrine were significantly decreased in animals both with and without inclusion of the organum vasculosum of the lamina terminalis. A similar effect was observed in intact vessels of dogs in which the circumventricular organ was spared but not in those with lesions that included this area. In contrast, angiotensin II-induced vasoconstriction was significantly decreased in the arteries with intact endothelium of both groups of lesioned animals. These data show that lesion of the anteroventral third ventricle area alters alpha 1-adrenergic and angiotensin II vascular responsiveness in isolated carotid artery rings with the possible participation of the endothelium.
Prevalence of Type A behavior in untreated hypertensive individuals.
Authors: Irvine J , Garner D M , Craig H M , Logan A G
Published: June 2012

Type A behavior has been associated with coronary heart disease as well as high cholesterol and smoking, major risk factors for coronary heart disease, but the data indicating a similar association with hypertension are inconsistent. Since past studies have usually based hypertension on a single blood pressure assessment or have often included treated hypertensive patients, this inconsistency is not surprising. The current study compared the prevalence of Type A behavior (assessed by Rosenman's structured interview) between 109 untreated hypertensive subjects and 109 age-, sex-, ethnic-, and occupation-matched normotensive subjects. Hypertension status was based on five repeated assessments over a 5-month period. Results indicated that Type A behavior is more prevalent in untreated, mildly hypertensive employed individuals than occupationally matched normotensive subjects. Type A component analysis confirmed the importance of hostility and certain vigorous voice stylistics in predicting cardiovascular conditions. These findings, taken together with the evidence linking Type A behavior with high cholesterol and cigarette smoking, further support the view that this behavior pattern is associated with increased risk of coronary heart disease.
Renal changes associated with cyclosporine in recent type I diabetes mellitus.
Authors: Rodier M , Ribstein J , Parer-Richard C , Mimran A
Published: June 2012

The effects of cyclosporine A treatment on arterial pressure and renal function were assessed in 11 young patients with type I diabetes of short duration. Cyclosporine was started at 7.5 mg/kg/day, progressively decreased to 6.3 mg/kg/day at 6 months, and then continued at a lower dose (4.1 mg/kg/day) for an additional 3 months in patients in whom remission of insulin dependency was obtained (n = 6). After 3 months of cyclosporine, a slight but significant increase in arterial pressure (+5.2 +/- 1.5 mm Hg), a rise in renal vascular resistance (approximately 20%), a decrease in glomerular filtration rate (approximately 25%), and a fall in filtration fraction were observed. Such changes were sustained after 6 and eventually 9 months of therapy. The decrease in glomerular filtration rate observed during cyclosporine treatment contrasted with the lack of change in simultaneously estimated creatinine clearance; in fact, the creatinine clearance/glomerular filtration ratio increased from 1.07 +/- 0.05% to 1.33 +/- 0.09% within 3 months of cyclosporine therapy, thus suggesting an enhanced tubular secretion of creatinine. Plasma renin activity and urinary excretion of kallikrein decreased significantly (approximately 50%), whereas plasma aldosterone concentration remained unaltered and plasma concentration of potassium increased during cyclosporine therapy. These changes were observed in the presence of a constant urinary excretion of sodium and potassium and a constant body weight. All parameters returned to pretreatment values within 3 months after cessation of cyclosporine. These results indicate that cyclosporine given for 6-9 months at a moderate dose causes a deleterious but reversible effect on arterial pressure and renal function in young diabetic patients.
Uptake of norepinephrine in an isolated artery from normotensive humans.
Authors: Wyse D G
Published: June 2012

Previous studies have suggested that catecholamine uptake may play a role in vascular responsiveness in hypertension. The current study was undertaken to characterize amine uptake and effects of its inhibition in an isolated human artery from normotensive subjects and to provide a basis for future study in hypertensive individuals. Accumulation of tritiated norepinephrine into the artery of normotensive subjects was time-dependent and 16.9-fold more than the incubation media concentration (1 microM) of amine after 60 minutes. There was a lesser accumulation of tritiated normetanephrine (3.1-fold), and it was not increased over time. Increasing the concentration of norepinephrine to 30 microM did not significantly change the proportional accumulation. Inhibition of neuronal uptake with cocaine (10 microM) reduced the average accumulation of both concentrations of tritiated norepinephrine to 3.9-fold (p less than 0.001). Inhibition of extraneuronal uptake with corticosterone alone (10 microM) had no significant effect on average accumulation of norepinephrine, and where combined with cocaine, there was no further effect of corticosterone. Neither cocaine nor corticosterone had any effects on accumulation of normetanephrine. In spite of elimination of approximately 75% of the uptake of norepinephrine, cocaine had very little potentiating effect on mechanical responses to exogenous norepinephrine and neurally released transmitter. Thus, norepinephrine uptake in human cystic artery is characteristic of neuronal uptake, but cocaine treatment has only a very modest potentiating effect on responsiveness to endogenous norepinephrine and no significant effect on responsiveness to exogenous amine.
Pathogenesis of hypertension in the sinoaortic-denervated spontaneously hypertensive rat.
Authors: Osborn J W
Published: June 2012

The present study was performed to examine the relation between the gain of the baroreceptor reflex and the pathogenesis of hypertension in the spontaneously hypertensive rat. Spontaneously hypertensive or Wistar-Kyoto rats underwent either sinoaortic baroreceptor denervation or sham denervation at 28-35 days of age. Four months later these rats were chronically instrumented for measurements of arterial pressure and heart rate. Sixty-minute computerized measurements of arterial pressure showed no difference between spontaneously hypertensive sham (163 +/- 5 mm Hg) and spontaneously hypertensive baroreceptor-denervated (166 +/- 5 mm Hg) rats, or Wistar-Kyoto sham (114 +/- 3 mm Hg) and Wistar-Kyoto baroreceptor-denervated (121 +/- 4 mm Hg) rats. The gain of baroreceptor reflex control of heart rate was assessed by measuring maximal heart rate responses to changes in arterial pressure elicited by bolus injection of phenylephrine and nitroprusside (gain = slope of linear regression equation of change in heart rate versus change in arterial pressure). Baroreceptor reflex gain was significantly higher in Wistar-Kyoto sham rats (-2.10 beats/min/mm Hg) than spontaneously hypertensive sham rats (-0.94 beats/min/mm Hg). Baroreceptor denervation significantly decreased baroreceptor reflex gain in both Wistar-Kyoto (-0.26 mm Hg) and spontaneously hypertensive (-0.22 beats/min/mm Hg) groups. Since baroreceptor denervation did not exacerbate the development of hypertension in adult spontaneously hypertensive rats or lead to hypertension in Wistar-Kyoto rats, we conclude that a primary dysfunction in the baroreceptor reflex alone is not responsible for the development of hypertension in this model.
Salt-induced plasticity in cardiopulmonary baroreceptor reflexes in salt-resistant hypertensive patients.
Authors: Trimarco B , Lembo G , Ricciardelli B , De Luca N , Rendina V , Condorelli G , Volpe M
Published: June 2012

To investigate the effects of salt loading on cardiopulmonary and arterial baroreceptor reflexes, 34 hypertensive patients underwent two 4-day periods with different dietary sodium intakes (70 and 370 meq/day). The patients were classified as salt-sensitive or salt-resistant depending on whether the mean arterial pressure value obtained on day 4 of high salt intake did or did not increase by 8% or more. In 22 patients cardiopulmonary and carotid baroreceptor reflexes were assessed during each dietary period by measuring the reflex responses to the application of -10 mm Hg lower body negative pressure and of +60 mm Hg increase in neck tissue pressure. Salt-resistant patients (n = 16) retained less sodium than salt-sensitive patients (n = 6) and showed a reduction in plasma norepinephrine and forearm vascular resistance during high sodium intake, whereas the salt-sensitive patients did not. During low sodium diet, no significant differences could be detected in the reflex responses to cardiopulmonary and carotid baroreceptor unloading between the two groups. High salt diet, however, potentiated the gain of cardiopulmonary baroreceptor reflex, which was expressed as the increase in plasma norepinephrine or forearm vascular resistance per millimeter of mercury decrease in pulmonary capillary wedge pressure, only in the salt-resistant hypertensive patients. In addition, the atrial natriuretic factor response to changes in pulmonary capillary wedge pressure was significantly enhanced by high salt intake only in the salt-resistant hypertensive patients. The reflex responses to carotid baroreceptor unloading were unaffected by salt loading in either group. In the remaining 12 patients, the hemodynamic effects of graded lower body negative pressure (-5, -10, -15 mm Hg) and neck tissue positive pressure (+30, +45, +60 mm Hg) were tested for both diets. Again, high salt intake significantly potentiated the cardiopulmonary baroreceptor reflex gain, expressed as the slope of the linear correlation between the changes in forearm vascular resistance (mm Hg/ml/min/100 g) and pulmonary capillary wedge pressure (mm Hg), in salt-resistant (from 3.8 +/- 0.9 to 7.2 +/- 1.0, p less than 0.05) but not in salt-sensitive patients (from 4.2 +/- 0.9 to 3.2 +/- 0.6, NS). In conclusion, the present study demonstrates that high salt diet potentiates cardiopulmonary baroreceptor reflexes and enhances atrial natriuretic factor response in salt-resistant but not in salt-sensitive hypertensive patients. The salt-induced plasticity of cardiopulmonary baroreceptor reflexes may exert a protective effect against the development of salt-induced hypertension by augmenting the reflex vasodilatory response to volume expansion.(ABSTRACT TRUNCATED AT 400 WORDS)
Expression of adrenal cytochromes P-450 in testosterone-induced hypertension.
Authors: Gallant S , Alfano J , Charpin M , Brownie A C
Published: June 2012

Chronic treatment of rats with the naturally occurring androgen, testosterone, leads to hypertension and cardiovascular disease. This effect is believed to be mediated through the adrenal gland and in particular by action on the steroid 11 beta-hydroxylase enzyme system. To study the possible mechanism of this effect, the enzyme system was examined at several time periods up to the time that hypertension develops. Rats were treated with testosterone (10 mg/day) for 3, 7, 21, and 42 days. Levels of cytochrome P-450(11) beta enzyme and messenger RNA (mRNA) were determined as well as 11 beta-hydroxylase enzyme activity. A significant decrease in enzyme activity was observed after 3 days of treatment. This correlates with a profound decrease in the level of cytochrome P-450(11) beta enzyme as determined by Western blot analysis. A large decrease in cytochrome P-450(11) beta mRNA was also observed after 3 days of treatment. All three parameters remained low throughout the treatment period. The decrease in 11 beta-hydroxylase enzyme activity appears to result from a lower enzyme level brought about by decreased concentrations of mRNA transcripts.
Ramiprilat enhances endothelial autacoid formation by inhibiting breakdown of endothelium-derived bradykinin.
Authors: Wiemer G , Schölkens B A , Becker R H , Busse R
Published: June 2012

We studied whether inhibition of angiotensin converting enzyme stimulates the formation of nitric oxide and prostacyclin in cultured human and bovine endothelial cells by an enhanced accumulation of endothelium-derived bradykinin. Nitric oxide formation was assessed in terms of intracellular cyclic GMP accumulation, prostacyclin release by a specific radioimmunoassay. Inhibition of angiotensin converting enzyme by ramiprilat dose- and time-dependently increased the formation of nitric oxide and prostacyclin. These increases, peaking within 10 minutes, were maintained for at least 60 minutes. The ramiprilat-induced cyclic GMP increase was completely abolished by the stereospecific inhibitor of nitric oxide synthase, NG-nitro-L-arginine. The B2-kinin receptor antagonist, Hoe 140 (0.1 microM), markedly attenuated the cyclic GMP accumulation and abolished the increase in prostacyclin release. The supernatant of endothelial cells, incubated with ramiprilat (0.3 microM) for 15 minutes, elicited a significant nitric oxide release (as assessed by a guanylyl cyclase assay) in untreated endothelial cells used as detector tissue. Preincubation of the detector cells with Hoe 140 completely abolished this nitric oxide release. These data indicate that cultured endothelial cells from different species are capable of producing and releasing bradykinin into the extracellular space in amounts that lead to a sustained stimulation of nitric oxide and prostacyclin formation, provided that bradykinin degradation is prevented by angiotensin converting enzyme inhibition. Thus, the protective effect of angiotensin converting enzyme inhibitors observed on endothelial vasomotor function in hypertension may be explained by the local accumulation of endothelium-derived bradykinin that acts in an autocrine and paracrine manner as potent stimulus for endothelial autacoid formation.