bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic and regional hemodynamic changes associated with anterior hypothalamic lesions in conscious rats.
Authors: Suarez D H , Pegram B L , Frohlich E D
Published: June 2012

Systemic and regional hemodynamics were determined with the radioactive microsphere technique either in conscious "sham-lesioned" Wistar rats or after bilateral electrolytic lesions of the nuclei of the anterior hypothalamus. Both mean arterial pressure (111 +/- 4 vs 152 +/- 3 mm Hg) and heart rate (376 +/- 15 vs 504 +/- 12 beats/min) were significantly increased 2 hours after lesioning (p less than 0.001). Although cardiac output tended to increase, it did not attain statistical significance; therefore this form of neurogenic hypertension is characterized by increased total peripheral resistance. Regional hemodynamics were measured 2 hours after placement of the lesions: skeletal muscle flow increased, renal cutaneous and splanchnic flows decreased, and brain and myocardial flows were preserved. These hemodynamic alterations were associated with significant elevations in plasma norepinephrine and epinephrine levels, and behavioral changes characterized by hypermotility, aggressitivity, and irritability, which resembled those seen during fighting and exercise.
Short-term systemic hemodynamic adaptation to beta-adrenergic inhibition with atenolol in hypertensive patients.
Authors: Simon G , Franciosa J A , Gimenez H J , Cohn J N
Published: June 2012

Early systemic hemodynamic adjustments to antihypertensive therapy with the cardioselective beta inhibitor, atenolol, were investigated in 12 hospitalized men, mean age 52 years, with uncomplicated mild-to-moderate essential hypertension. Twice daily measurements of cardiac output (CO) by CO2 rebreathing, blood pressure by cuff, and heart rate were performed in all subjects for 3 days before and 5 days after initiation of oral atenolol therapy (50 or 100 mg daily). Cardiac output by CO2 rebreathing was checked with dye dilution just before, and 4 hours and 4 days after the start of therapy. Plasma volume (radioiodinated albumin) was measured before therapy and on Day 5 of therapy. The CO results obtained with the two methods were not significantly different (r = 0.88, p less than 0.01, n = 12). A reduction in heart rate, 18 +/- 2 beats/min (mean +/- SE), occurred in all patients while taking atenolol. By 4 hours after the first dose of atenolol, CO fell from 5.49 +/- 0./30 to 4.24 +/- 0.21 liters/min (p less than 0.01), while the control mean arterial pressure (MAP) of 108 +/- 4 mm Hg was not significantly changed, 110 +/- 4 mm Hg. At 24 hours, CO returned near baseline (5.10 +/- 0.21 liters/min) but MAP was reduced (95 +/- 3 mm Hg, p less than 0.001) and remained so thereafter. CO remained at baseline at 48 hours (5.50 +/- 0.29 liters/min) but fell again (p less than 0.01) to 4.81 +/- 0.11 on Day 4 and to 4.68 +/- 0.25 liters/min on Day 5 of atenolol therapy. Plasma volume, 3110 +/- 100 ml before therapy, was reduced to 2850 +/- 100 by Day 5 of atenolol therapy (p less than 0.01). The findings indicate a delayed onset of the antihypertensive action of atenolol. The transient return to baseline of CO on Day 2 and 3 of atenolol therapy suggests a reverse autoregulatory adjustment to the initial fall in CO.
Analysis of calcium handling in erythrocyte membranes of genetically hypertensive rats.
Authors: Devynck M A , Pernollet M G , Nunez A M , Meyer P
Published: June 2012

Calcium handling by erythrocyte membranes was compared in genetically hypertensive (SHR) and normotensive (WKR) rats by direct measurement of calcium binding, passive influx, and adenosine triphosphate (ATP)-dependent extrusion. The SHR erythrocyte membranes exhibited the following abnormalities: 1) the binding capacity of the high affinity Ca2+-binding sites located on the inner side of the membrane was 0.84 +/- 0.07 nmole/mg protein compared with 1.17 +/- 0.08 nmole/mg protein in WKR, 2) ATP-dependent Ca2+ extrusion, measured as the Ca2+ influx into inside-out vesicles, was also lower than the WKR, as was the La3+ -sensitive, Ca2+ -dependent hydrolysis, indicating reduced activity of the calcium pump; 3) the passive calcium influx into ATP-depleted red blood cells was slightly accelerated. these abnormalities in Ca2+ binding and transport probably enhanced intracellular Ca2+ concentration, and were observed under both prehypertensive an hypertensive conditions, in 3-week-old and adult SHR respectively. Similar membrane defects in excitable cells may help to explain the pathogenesis of hypertension, since they may increase vascular tone and/or catecholamine release.
Vasopressin release does not contribute to pressor action of enkephalin in SHR.
Authors: Rockhold R W , Crofton J T , Share L
Published: June 2012

The effects of injection of a peptidase-resistant analog of methionine-enkephalin, [D-ala2]-methionine-enkephalin, on blood pressure (BP), heart rate, and vasopressin release were studied in spontaneously hypertensive rats (SHR). Intravenous injection of [D-Ala2]-methionine-enkephalin (DAME) increased BP in both SHR and normotensive Wistar-Kyoto (WKY) controls, with a significantly greater increase in hypertensive rats. Intracerebroventricular injection of DAME produced a biphasic increase in BP and an increase in heart rate in both groups. The initial pressor effect was significantly greater in the SHR, Plasma vasopressin levels in SHR were depressed relative to both untreated hypertensive rats and animals given vehicle control injections. Intravenous pretreatment with a vasopressin vasopressor antagonist, [l-(beta-mercapto-beta-beta-cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine] arginine-vasopressin, did not block either component of the central enkephalin response in hypertensive rats. These date indicate that central enkephalin injection does not release vasopressin and that SHR are hyperresponsive to enkephalin. It is concluded that pressor systems other than that of vasopressin mediate the enkephalin-induced cardiovascular effects.
Exaggerated sympathetic responses to bradykinin in spontaneously hypertensive rats.
Authors: Buñag R D , Takahashi H
Published: June 2012

Possible defects in blood pressure (BP) regulation were studied by recording responses to centrally-administered bradykinin. Pressor effects accompanied by increased sympathetic nerve activity were elicited by intracerebroventricular injections in intact rats, but significant differences between Kyoto-Wistar normotensive (KNR) and spontaneously hypertensive rats (SHR) were not detected. By contrast, intracarotid injections into cross-perfused head preparations consistently produced more prominent systemic effects in SHR than in KNR, and these differences became even more pronounced following carotid denervation. After destruction of central noradrenergic neurons in KNR by intracerebroventricular injection of 6-hydroxydopamine (6-OHDA), responses to bradykinin became the same as those in SHR. These results are in accord with the interpretation that alpha-adrenergic mechanisms for blood pressure regulation in supramedullary brain areas no longer function normally in SHR and that a similar dysfunction can be induced in KNR by pretreatment with 6-OHDA.
Analogs of phosphatidylcholine: alpha-adrenergic antagonists from the renal medulla.
Authors: Smith K A , Prewitt R L , Byers L W , Muirhead E E
Published: June 2012

Antihypertensive polar renomedullary lipid (APRL), a conglomerate of 1-0-alkyl-2-acetoyl-glycero-3-phosphocholine analogs, ws tested in 4- to 6-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats using microcirculatory techniques. APRL (0.5 ug/ml), when added to the solution bathing the cremaster muscle, caused significant changes in the diameter, red blood cell velocity, and blood flow in both groups of rats, for arterioles and venules. Arteriolar changes in diameter were significantly greater (p less than 0.05) in SHR than in WKY. Micropipette application of APRL indicated a dose-dependent response for arterioles and venules in both groups. Moreover, the potent nature of this compound was demonstrated. Relative potency of APRL given intravenously was tested in 10- to 12-week-old SHR and WKY. The response curve was shifted significantly to the left for SHR (p less than 0.01). APRL interaction with known controllers of blood flow was tested in SHR. Blockade of cholinergic, beta-adrenergic, or histaminergic receptors did not inhibit APRL action. blockade of prostaglandin or bradykinin synthesis did not prevent depression of blood pressure by APRL. APRL (40 ug/kg) inhibited (p less than 0.001) the pressor response to norepinephrine (1-10 ug/kg) but not to angiotensin II (4 ug/kg). The present study provides direct evidence that APRL is a vasodilator with increased potency in SHR hypertension. The acute vascular response may be mediated by alpha-adrenergic antagonism.
Pre- and postcapillary vascular responses to sympathetic nerve stimulation in DOCA-hypertensive dogs.
Authors: Brock T A , Fleming B P , Diana J N
Published: June 2012

Measurements of precapillary resistance (Ra),postcapillary resistance (Rv), and mean capillary hydrostatic pressure (Pci) were made during sympathetic nerve stimulation (SNS) under constant-flow perfusion in isolated hindlimbs from deoxycorticosterone acetate (DOCA)-hypertensive dogs. We found that both pre- and postcapillary vascular responses to SNS were greater in the DOCA-hypertensive group when compared to the control group. Intraarterial injections of norepinephrine produced a dose-response curve for precapillary vessels in the hypertensive group that was asymmetrically shifted to the left (increased slope) and exhibited a significant decrease in vasoconstrictor threshold. these results, coupled with our earlier observations, suggest that the hyperresponsiveness of the precapillary segment in DOCA-hypertensive dogs could be attributed to both structural and intrinsic alterations of the resistance vessels. We present evidence that suggests, however, that the increased postcapillary resistance with SNS may be explained by a structural alteration causing a decrease in the diameter of existing postcapillary vessels, or may be due to a decrease in the actual number of postcapillary vessels, or both. It is concluded that in this model of hypertension, postcapillary vascular changes also contribute to the overall increase in total peripheral resistance.
Ultrastructural characteristics of endothelial permeability in chronic hypertension.
Authors: Majack R A , Bhalla R C
Published: June 2012

This study examined characteristics of paracellular and pinocytotic permeability pathways across the middle cerebral artery endothelium of 12- to 16- month-old spontaneously hypertensive rats (SHR). Interendothelial junctions in SHR, like those of age-matched Wistar-Kyoto controls, were impermeable to lanthanum and horseradish peroxidase (HRP) tracers. Freeze-fracture preparations revealed that interendothelial junctions of chronically hypertensive rats are characterized by a twofold increase over controls in the number of tight junctional strands and the mean apical-basal depth. It is believed that this tight junctional hypertrophy may function to increase adhesive forces between neighboring endothelial cells, and may play a role inthe prevention of hypertension-induced paracellular permeability increases. Morphological and tracer studies of pinocytotic pathways indicated that, it the middle cerebral artery, endothelial vesicular transport activity is not increased during chronic hypertension. No evidence was found to indicate the presence of transendothelial permeability channels across control or hypertensive arterial endothelium. Thus, increased transendothelial permeability, commonly observed in acute hypertension, does not appear to occur during chronic hypertension, at least in the middle cerebral artery. Our findings suggest that the arterial endothelium may undergo structural (tight junctional) adaptation in response to prolonged hypertension.
Kinetics of active sodium transport in aortas from control and deoxycorticosterone hypertensive rats.
Authors: Jones A W
Published: June 2012

The efflux of sodium (24Na) was measured in the aortas from control and deoxycorticosterone (DOCA) hypertensive rats. Measurements were also made of aortic water content, extracellular space, and electrolyte contents. The objective was to determine the kinetics for potassium (K)-stimulated (active) transport of sodium and to determine which, if any, kinetic parameters are altered during DOCA hypertension. The K-stimulated efflux of 24Na (about 50% of the total) exhibited a sigmoidal dependence on extracellular K ([K]0), and agreed well with a model based on the cooperative interaction between Na and K at transport sites. Half saturation was achieved at [K]0 = 1.7 to 2.8 mM for the various groups. The maximum efflux was increased 40% to 50% by DOCA (p less than 0.01). Aortas from control and DOCA-treated rats had similar [Na]cell (11 mM/liter cell H2O, for physiological solution) under conditions of partial or complete Na loading. Active transport of Na showed a sigmoidal dependence on [Na]cell. Half saturation was achieved at [Na]cell = 20 to 24 mM/liter cell H2O in control and DOCA aortas. The maximum efflux was elevated 46% by DOCA treatment (p less than 0.01). It is concluded that DOCA hypertension is associated with an increased leak of ward of shift of the transport curves as a result of increased maximal transport. The net effect is to maintain [Na]cell relatively constant in DOCA hypertensives under physiological conditions.
Effect of chronic treatment of spontaneously hypertensive rats with D 600.
Authors: Pang C C , Sutter M C
Published: June 2012

The effects of chronic treatment of spontaneously hypertensive rats (SHR) with methoxyverapamil (D 600) on blood pressure (BP) and on the in vitro contractile response of aortic and portal vein strips of rats were examined. D 600, prepared as the free base and dissolved in sesame oil, was injected subcutaneously daily into SHR to maintain the systolic blood pressure (SBP) at less than 130 mm Hg for 24 hours after injections. The dose required increased progressively from 4 to 8.5 mg/day/rat. As controls, normotensive rats (WKY) and untreated SHR received daily injections of the vehicle. After 2 weeks, aortic and portal vein strips were prepared from each rat for studies of cumulative dose-response curves to norepinephrine (NE) in Krebs' solution containing normal (2.5 mM) and low (0.2 and 0.4 mM) calcium (Ca). Chronic treatment with D 600 restored to control values the ordinarily depressed contractile response to NE and increased the ED50 values for NE (i.e., the NE dose that produces 50% of the maximum response) of aortic strips from SHR in nord-mal and low Ca. Portal veins from SHR showed increased spontaneous activity, supernormal responses to NE, and decreased ED50 values for NE that were all exaggerated by chronic D 600 treatment. These results imply that SHR developed a tolerance to D 600 associated with enhanced contractility of vascular smooth muscles.
Noradrenergic mechanisms in the brain and peripheral organs of normotensive and spontaneously hypertensive rats at various ages.
Authors: Patel K P , Kline R L , Mercer P F
Published: June 2012

Previous studies of noradrenergic mechanisms in spontaneously hypertensive rats (SHR) have yielded conflicting results, as many have used: 1) rats of only one age; 2) a single organ such as heart or brain; or 3) either Wistar-Kyoto (WKY) or an outbred normotensive control rat. We have studied the turnover of norepinephrine (NE) in three brain areas (cortex, hypothalamus, brain stem) and three peripheral organs (duodenum, skeletal muscle, kidney) of SHR, WKY, and Wistar rats at 5, 9, and 18 weeks of age. The rate of decline of norepinephrine [NE] in tissue was determined with a fluorescence assay at 0, 2, 4, and 8 hours after inhibition of tyrosine hydroxylase with alpha-methyltyrosine. Differences in NE turnover were inferred by comparing slopes of regression lines calculated for the plot of log [NE] (expressed as a percent of the initial concentration) vs time. Systolic arterial pressure of SHR was similar to that of WKY and Wistar rats at 5 weeks of age, but increased to 150 mm Hg by 9 weeks and reached an average of 190 mm Hg by 18 weeks. The turnover of NE in 5-week-old SHR compared to two normotensive strains was significantly lower in the cortex and significantly higher in the kidney and skeletal muscle. By 9 weeks, in SHR, NE turnover had increased significantly in the hypothalamus and brain stem, while decreasing significantly in the kidney and duodenum. No such changes were seen in these organs of WKY or Wistar rats when comparing turnover of NE at 5 and 9 weeks. At 18 weeks, there were no further differences in the organs of SHR when compared to values obtained at 9 weeks. These data support the hypothesis that the turnover of NE may be altered in central and peripheral organs of young SHR, and may initiate or contribute to the development of hypertension. Changes in turnover of NE in the brain and peripheral organs between 5 and 9 weeks in SHR suggest compensatory responses to increasing arterial pressure; however, similar changes in turnover were not seen between 9 and 18 weeks, although arterial pressure continued to increase.
Altered in vitro uptake of norepinephrine by cardiovascular tissues of spontaneously hypertensive rats. Part 1. Mesenteric artery.
Authors: Rho J H , Newman B , Alexander N
Published: June 2012

The incorporation of tritiated norepinephrine (NE) by mesenteric arteries from spontaneously hypertensive rats (SHR) of the Okamoto strain and from age-matched Wistar Kyoto (WKY) controls was studied. The arteries were incubated with tritiated NE, and fractions were isolated by differential and sucrose density gradient centrifugations. The amount of radioactivity present in certain subfractions (P3 pellet) of the SHR arteries was significantly higher than that of WKY arteries. When the P3 subfraction was lysed and subjected to sucrose density gradient centrifugation, the tritiated NE was found to ba associated with the 0.4-0.5 M interface. Electron micrographs of the P3 subfractions revealed a variety of vesicular structures which might represent storage sites for the tritiated NE. Although a number of factors could account for the finding of enhanced incorporation into mesenteric artery subfractions of hypertensive rats, the finding is compatible with the work of others who found increased ATPase activity in mesenteric arteries of SHRs, since ATPase is known to activate vesicular NE uptake.
Myofilament-polyribosome association in muscle cells of rat left atrium after short-term hypertension.
Authors: Aguas A P , Abecasis P , Mariano V , Nogueira da Costa J
Published: June 2012

Hypertension was induced in uninephrectomized Wistar rats by administration of deoxycorticosterone acetate (DOCA) and by addition of NaCl to their drinking water. The ultrastructure of atrial and ventricular cells of left hearts was compared after short-term (2 and 6 weeks) increased blood pressure. No morphological features could distinguish cells of treated animals from cells of normotensive rats after 2 weeks of treatment. The sarcoplasm of the atrial cells of 6-week-treated hypertensive rats presented an abnormally high number of helical arrangement of ribosomes often associated with abundant unorganized thick filaments, irregular nuclear profiles showing foldings and convolutions, and enlarged mitochondria. The only fine structural changes observed in the ventricular cells of the same animals was a moderate mitochondrial enlargement. The described alterations of atrial cells probably correspond to enhanced synthesis of contractile elements associated with increased nuclear-cytoplasmic exchanges; their absence in ventricular cells suggests that short-term and moderate pressure overload induces adaptative changes in left atrial cells at a stage when ventricular cells have morphological characteristics close to normal cells.
Reversal of Microvascular Rarefaction and Reduced Renal Mass Hypertension
Authors: Rieder Mark J. , Roman Richard J. , Greene Andrew S.
Published: June 2012

Abstract
This study examined the microcirculatory and renin-angiotensin system changes following the reversal of hypertension in reduced renal mass rats. Nine-week-old Sprague-Dawley reduced renal mass rats were placed on a low or high sodium diet for 4 or 8 weeks or a combination of 4 weeks of high sodium followed by 4 weeks of low sodium. Blood pressure was directly measured during the development of hypertension and its reversal. Plasma renin activity, angiotensin-converting enzyme activity, and angiotensin II concentrations were measured throughout the experiment. The cremaster and hindlimb muscles were removed, and microvascular density was determined by quantitative stereology. Four weeks of high sodium increased blood pressure (152±7 mm Hg) and reduced microvessel density (13.7%). Reduced renal mass hypertension was rapidly reversed after the rats were returned to a low sodium diet (124±7 mm Hg after 3 days), and microvascular density returned to control levels. After 4 weeks of high sodium, circulating plasma renin activity and angiotensin II fell by 94% and 82%, respectively. Plasma angiotensin-converting enzyme activity was increased after 2 weeks of high sodium but returned to control levels after 4 weeks of high sodium. This study demonstrates that microvascular density is reduced in reduced renal mass hypertensive rats following exposure to high sodium diet and this is associated with a fall in circulating plasma renin activity and angiotensin II levels. Microvascular density can return to normal levels after a reactivation of the circulating renin-angiotensin system. This study provides further evidence for the hypothesis that modulation of the renin-angiotensin system is important in the regulation of microvascular structure.
Endogenous Endothelin Modulates Blood Pressure, Plasma Volume, and Albumin Escape After Systemic Nitric Oxide Blockade
Authors: Filep János G.
Published: June 2012

Abstract
To assess whether acute nitric oxide (NO) blockade could unmask the vascular actions of endogenous endothelin, we tested the effects of the endothelin type A/type B (ET
A
/ET
B
) receptor antagonist bosentan and the selective ET
A
antagonist FR 139317 on blood pressure, plasma volume, and albumin escape after inhibition of NO synthesis with
N
G
-nitro-
l
-arginine methyl ester (L-NAME). Conscious, chronically catheterized rats received L-NAME in the absence and presence of 17.4 μmol/kg (10 mg/kg) bosentan or 3.8 μmol/kg (2.5 mg/kg IV, 10 minutes before L-NAME) FR 139317. Red blood cell volume and plasma volume were determined with chromium-51–tagged erythrocytes and iodine-125–labeled albumin, respectively. L-NAME (0.46 to 7.42 μmol/kg [0.125 to 2 mg/kg]) induced a dose-dependent increase in blood pressure, which was attenuated by 60% and 48% with bosentan and FR 139317, respectively (
P
<.01). L-NAME (7.42 μmol/kg) also increased hematocrit. This effect was associated with an increase in total-body albumin escape, which is reflected by a 14% reduction in plasma volume. Red blood cell volume remained unchanged. L-NAME promoted albumin escape primarily in the lung, heart, liver, kidney, and gastrointestinal tract. Both bosentan and FR 139317 markedly reduced these effects of L-NAME. Furthermore, L-NAME increased plasma levels of immunoreactive endothelin-1 from 8.6±0.4 (n=10) to 14.7±1.4 pg/mL (n=9,
P
<.01). These results demonstrate that the pressor response, losses in plasma volume, and increase in albumin escape observed after inhibition of NO synthesis are in part the consequence of unmasking the actions of endogenous endothelin, which are mediated predominantly via ET
A
receptors. These findings suggest a role for endogenous endothelin in the regulation of vascular functions in conditions when NO formation by endothelial cells is impaired.
Angiotensin II and Myocyte Growth
Authors: Sil Subha Sen Parames
Published: June 2012

Abstract
Angiotensin II (Ang II) has been implicated in stimulating myocyte growth in vitro, but the mechanism for such stimulation is still an open question. To understand the role of Ang II, we studied its effect on protein synthesis in rat neonatal and adult myocytes. Ang II (10
−8
mol/L) stimulated protein synthesis in neonatal myocytes by 43±3.5% over control. To prevent the proliferation of fibroblasts, bromodeoxyuridine was added, and protein synthesis in neonatal myocytes was reduced to 21±2.2% over control. In adult myocytes (cultured without bromodeoxyuridine), Ang II stimulated [
3
H]leucine incorporation by 24±2.3% over control; with bromodeoxyuridine, that stimulation was reduced significantly (13±0.93% over control). These data suggest that the presence of fibroblasts in the cultures may control myocyte growth. When supernatant from pure fibroblast culture was added to myocyte preparations, a significant increase (49.8±3.5% over control) in protein synthesis occurred. Pretreatment of these fibroblasts with Ang II (10
−8
mol/L) further stimulated protein synthesis, suggesting that Ang II directly stimulates the production of a factor from fibroblasts. The stimulatory effect of Ang II on the release of the factor can be completely blocked by pretreatment with losartan, an Ang II receptor (AT
1
) blocker. Our data are the first to demonstrate a paracrine effect of a fibroblast-derived factor that modulates myocyte growth. Fibroblast-derived factor loses its biological activity by (1) tryptic digestion, (2) exposure to pH below 4.0 and above 9.0, and (3) heating to 95°C. The molecular weight of the factor is approximately 65 kD. The antibodies against fibroblast growth factor (both acidic and basic) could not inhibit this factor’s stimulatory effect. Furthermore, this factor is heart specific and is produced at least up to the 16th passage of neonatal rat heart fibroblasts. Skin fibroblasts, aortic endothelial cells, and aortic smooth muscle cells do not produce this protein. Our data suggest that the observed myocyte growth by Ang II comes about via fibroblast-derived factor, which is increased by Ang II. Cross talk between fibroblasts and myocytes is an important factor in stimulating myocyte growth by Ang II.
Downregulation of Renin Gene Expression by Interleukin-1
Authors: Petrovic Nenad , Kane Colleen M. , Sigmund Curt D. , Gross Kenneth W.
Published: June 2012

Abstract
The As4.1 cell line was established from a mouse kidney tumor by transgene-targeted tumorogenesis. These cells express high levels of renin mRNA from their endogenous renin gene and release approximately eightfold-more prorenin than active renin in culture. Levels of renin mRNA in As4.1 cells are decreased in a dose-dependent manner by the addition of physiological concentrations of cytokine interleukin-1 to the media. Stability of renin mRNA and initial rates of release of active renin and prorenin were not significantly altered by interleukin-1. In contrast, transcription initiated from a construct that consisted of 4.1 kilobases of renin 5′ flanking sequence fused to a reporter gene (chloramphenicol acetyltransferase) was markedly inhibited by interleukin-1. On the basis of our findings, we conclude that downregulation of renin synthesis caused by interleukin-1 occurs primarily at the level of transcription and that DNA sequence or sequences mediating that effect are positioned within 4.1 kilobases upstream of the renin gene. The physiological relevance of this regulation is related to the events that occur during septic shock, characterized by hypotension, cardiovascular collapse, multiple organ failure, and high mortality. Unexpectedly, hypotension associated with septic shock does not lead to activation of the renin-angiotensin system. The hypotension in septicemia is believed to be mediated by the combined action of many modulators including cytokines, and data presented here suggest direct involvement of interleukin-1 in this process.
Role of Cardiac Output in Ethanol-Evoked Attenuation of Centrally Mediated Hypotension in Conscious Rats
Authors: El-Mas Mahmoud M. , Abdel-Rahman Abdel A.
Published: June 2012

Abstract
Our previous studies have shown that ethanol selectively counteracts centrally mediated hypotensive responses. This study investigated the role of cardiac output and peripheral resistance in the antagonistic interaction between ethanol and antihypertensive drugs. Changes in blood pressure, heart rate, cardiac index, stroke volume, and peripheral resistance elicited by clonidine and subsequent ethanol or saline administration were evaluated in conscious rats. The aortic barodenervated rat was employed because it exhibits greater hypotensive responses to clonidine compared with the intact rat. Aortic barodenervation elicited acute rises in blood pressure, heart rate, and peripheral resistance, whereas cardiac index and stroke volume were not altered. The blood pressure of conscious aortic barodenervated rats returned to sham-operated levels by 48 hours due to concomitant reductions in cardiac index and stroke volume; the peripheral resistance, however, remained significantly elevated. Clonidine (30 μg/kg, IV) elicited greater decreases in blood pressure in aortic barodenervated compared with sham-operated rats. The hypotension was caused by decreases in cardiac index and stroke volume because peripheral resistance did not change. Ethanol (1 g/kg, IV) counteracted the hypotensive effect of clonidine and raised blood pressure to levels higher than preclonidine values. Significant (
P
<.05) increases in cardiac index and stroke volume and decreases in peripheral resistance accompanied the pressor effect of ethanol. Additional control groups were included in the study to determine the selectivity of the interaction. A dose of hydralazine (0.5 mg/kg, IV) was used that produced similar hypotension to that evoked by clonidine in aortic barodenervated rats. Hydralazine-evoked hypotension was similar in denervated and control rats and resulted from significant reductions in peripheral resistance. Reflex increases in heart rate and stroke volume and hence cardiac output were observed. Ethanol given after hydralazine produced a short-lived pressor effect (<5 minutes versus 40 minutes in the case of clonidine) and counteracted the sympathetically mediated increases in cardiac output, stroke volume, and heart rate. These findings support our hypothesis that ethanol selectively counteracts hypotensive responses of central origin by reversing the reduction in cardiac output elicited by clonidine.
Relations of Left Ventricular Geometry and Function to Body Composition in Children With High Casual Blood Pressure
Authors: de Simone Giovanni , Mureddu Gian Francesco , Greco Rosanna , Scalfi Luca , Esposito Del Puente Antonella , Franzese Adriana , Contaldo Franco , Devereux Richard B.
Published: June 2012

Abstract
To determine whether abnormal casual blood pressure (BP) is associated with left ventricular (LV) abnormalities in children, 190 6- to 11-year-old children (77 girls, 113 boys) were studied at a school site in Naples, Italy, by limited echocardiography and bioelectric impedance to calculate fat-free body mass (FFM). Single-visit BP measurements (defined as casual BP) were high (based on the Italian tables of BP) in 34 children (18%; 9 girls, 25 boys; 133±8/81±10 mm Hg) and obesity was present in 44 (23%; 15 girls, 29 boys). Sex- and age-independent risk of high casual BP value was 2.9-fold (odds ratio) greater in obese than in normal-weight children (95% confidence interval, 1.3 to 6.5;
P
<.01). LV mass (as both absolute value and normalized for height
2.7
or FFM) was higher and relative wall thickness increased in children with high casual BP (all
P
<.01). Prevalence of LV hypertrophy was 21% among children with high casual BP (
P
<.004 versus 4.3% in normal group). Risk of LV hypertrophy was 5.5-fold higher in the presence of high casual BP (
P
<.004), whereas obesity, age, and sex did not have independent effects. Endocardial shortening was slightly higher in children with high casual BP (36.8±8.2%) than in children with normal BP (34.3±4.8%,
P
<.02), whereas midwall shortening was identical in the two groups (20%). Both endocardial shortening and midwall shortening were negatively related to end-systolic stress (
r
=−.62, SEE=3.8% and
r
=−.32, SEE=2.4% in normal children). Shortening as a percentage of predicted from wall stress was increased in children with high casual BP at the endocardial level (
P
<.001), whereas it was normal at the midwall. Therefore, (1) casual detection of high BP in school children is associated with LV geometric abnormalities similar to those found in adults with sustained hypertension (LV hypertrophy, concentric pattern); (2) similar to in adult hypertension, endocardial chamber function in children is supranormal; and (3) in contrast to findings in adults, midwall shortening is normal in children with high casual BP.
Salt and Blood Pressure Responses to Calcium Antagonism in Hypertensive Patients
Authors: Weir Matthew R. , Hall Pamela Sue , Behrens M. Theresa , Flack John M.
Published: June 2012

Abstract
Since salt intake may affect blood pressure response to antihypertensive drugs, an individual’s salt-sensitivity status may be an important consideration in the selection of a medication. The purpose of this single-blind study was to assess the impact of salt sensitivity on the antihypertensive effects of isradipine. A total of 21 evaluable hypertensive patients (10 white, 11 black) 35 to 73 years of age (mean 55.9 years) were randomized to a low-salt diet (mean 24-hour urine sodium 100±14 mmol) or a high-salt diet (mean 24-hour urine sodium 210±22 mmol) for 7 weeks, followed by crossover to the other diet after a 2-week washout period. On each diet regimen, patients received placebo for 2 weeks, followed by optimal titration of isradipine (2.5 to 10 mg BID) for blood pressure control during the last 5 weeks. On the high-salt diet, salt-sensitive hypertensives (mean arterial blood pressure increase ≥5 mm Hg, n=5) exhibited a systolic/diastolic blood pressure change of −18.7/−19.6 mm Hg from 157.2/102.9 mm Hg after 5 weeks of isradipine treatment, whereas on a low-salt diet, blood pressure change was −6.9/−12.0 mm Hg from 148.7/97.3 mm Hg. Non–salt-sensitive patients (n=16) exhibited a systolic/diastolic blood pressure change of −12.6/−7.6 mm Hg from 155.3/98.6 mm Hg on the high-salt diet and −19.2/−10.9 mm Hg from 161.0/102.6 mm Hg on the low-salt diet after treatment with isradipine. The absolute blood pressure attained in both salt-sensitive and non–salt-sensitive patients was almost identical with isradipine therapy despite variation in dietary salt, although slightly higher doses of isradipine were required in the salt-sensitive group. Consequently, isradipine, and perhaps calcium antagonists in general, manifests a more robust blood pressure–lowering effect in the setting of high sodium intake. This effect does, however, appear to be largely confined to individuals who are salt sensitive.
Increased Density of Renal Amylin Binding Sites in Experimental Hypertension
Authors: Wookey Peter J. , Cao Zemin , van Geenen Rutger C.I. , Voskuil Michiel , Darby Ian A. , Komers Radko , Cooper Mark E.
Published: June 2012

Abstract
High-affinity binding sites for the pancreatic β-cell hormone amylin have been reported in the kidney, and it has been postulated that these sites may be involved in the genesis of hypertension. In the present study, we have used in vivo injection of
125
I-amylin and in vitro autoradiographic techniques to assess renal amylin binding in both a genetic and a surgically induced model of hypertension. In the spontaneously hypertensive rat (SHR) at 6 weeks of age, before the rise in systolic blood pressure, there was a 36% increase in density of amylin binding compared with their normotensive counterpart, the Wistar-Kyoto rat (WKY). In SHR, there was a further increase in the density of amylin binding (to 53% greater) as the systolic blood pressure rose between 6 and 12 weeks of age. Histological examination of kidneys from SHR at 12 weeks of age revealed staining for a brush border glycoprotein, normally restricted to the proximal tubules, extending from the urinary pole into half of the epithelial lining of the glomerular capsule. In contrast to WKY, these cells also bound
125
I-amylin with high density in SHR. In a rat model of renal ablation and hypertension, systolic blood pressure correlated with the density of
125
I-amylin binding in the renal cortex (
r
=.54,
P
=.003, n=28). The changes in amylin binding reported here suggest a possible role for this peptide and/or activation of its receptor in the genesis as well as the maintenance of hypertension.
Intracellular Ca
2+
Handling and Vulnerability to Ventricular Fibrillation in Spontaneously Hypertensive Rats
Authors: Zaugg Christian E. , Wu Shao T. , Lee Randall J. , Wikman-Coffelt Joan , Parmley William W.
Published: June 2012

Abstract
Spontaneously hypertensive rats (SHR) with ventricular hypertrophy show an increased vulnerability for the development of potentially lethal ventricular arrhythmias such as ventricular fibrillation (VF). The mechanisms of this increased vulnerability are not fully understood but may be related to abnormal intracellular Ca
2+
([Ca
2+
]
i
) handling under stress conditions. We therefore investigated whether [Ca
2+
]
i
handling is abnormal in hypertrophied hearts of SHR without heart failure during stimulation stress, and if so whether abnormal [Ca
2+
]
i
handling is a determinant of the increased vulnerability to VF in SHR. [Ca
2+
]
i
was measured by indo-1 surface fluorescence in perfused hearts of 8- to 10-month-old control Wistar-Kyoto rats (WKY) and age-matched SHR. The state of [Ca
2+
]
i
handling was analyzed during three different forms of stimulation stress: rapid pacing, the long rest period after cessation of rapid pacing, and preprogrammed ventricular stimulation that was simultaneously used for the determination of VF threshold. The pulse number VF threshold was used as an index to determine vulnerability to VF and to analyze the relationship of [Ca
2+
]
i
handling to vulnerability. Although VF thresholds were lower in SHR than in WKY, we found that both demonstrated similar [Ca
2+
]
i
handling during stimulation stress. The extent and rate of [Ca
2+
]
i
accumulation during rapid pacing and those of the [Ca
2+
]
i
decline after cessation of pacing were similar in SHR and WKY. In addition, the relationship between [Ca
2+
]
i
and VF threshold was unaltered in SHR. Thus, we conclude that [Ca
2+
]
i
handling is normal in hypertrophied hearts of SHR without heart failure during stimulation stress and that it is not a determinant of the increased vulnerability to VF in SHR.
Potentiation of the Hypotensive Effect of Bradykinin by Short-term Infusion of Angiotensin-(1-7) in Normotensive and Hypertensive Rats
Authors: Lima Celso V. , Paula Renata D. , Resende Fernanda L. , Khosla Mahesh C. , Santos Robson A. S.
Published: June 2012

Abstract
In this study we evaluated the effect of angiotensin-(1-7) on the hypotensive action of bradykinin (BK) in normotensive rats, renal hypertensive rats (RHR), and spontaneously hypertensive rats (SHR). In addition, we evaluated the effect of angiotensin-converting enzyme (ACE) inhibition with enalaprilat treatment (10 mg/kg IV) on the BK-potentiating activity of Ang-(1-7). Renal hypertension was produced by aorta coarctation between the origin of renal arteries. Ang-(1-7) (0.3 pmol/min) or saline (0.9% NaCl, 5 μL/min) was infused intravenously in conscious male Wistar rats, adult SHR, or RHR. Intravenous bolus injections of BK (0.1 to 1.6 nmol in RHR and SHR; 0.625 to 5 nmol in Wistar rats) were made before and within 30 and 60 minutes of Ang-(1-7) infusion. Ang-(1-7) infusion did not change mean arterial pressure (MAP) of Wistar rats (MAP=97±3 mm Hg), RHR (MAP=173±3 mm Hg), or SHR (MAP=177±5 mm Hg). In Wistar rats, Ang-(1-7) increased the BK hypotensive effect by 24±6% within 60 minutes of infusion. No significant changes were observed at 30 minutes of infusion. In additional groups of rats, Ang-(1-7) (5 pmol/min, n=5) was infused alone or combined with its selective antagonist D-Ala
7
-Ang-(1-7) (A-779) (5 pmol/min, n=6). The bradykinin-potentiating activity of Ang-(1-7) was completely abolished by A-779. In SHR and RHR, Ang-(1-7) significantly increased the hypotensive effect of BK by 59±8% and 57±9.8%, respectively, within 60 minutes of infusion. No significant changes were observed with saline infusion. In Wistar rats, enalaprilat treatment increased the BK-potentiating activity of Ang-(1-7) transforming the effect of 0.3 pmol/min into that observed with a rate 16-fold higher (5 pmol/min). On the other hand, in SHR enalaprilat did not change the Ang-(1-7) effect, while it abolished the BK potentiation in RHR. Our data show that the BK-potentiating activity of Ang-(1-7) is preserved and even augmented in hypertensive rats. The finding that the BK-potentiating activity of Ang-(1-7) could be demonstrated at a very low infusion rate suggests that this angiotensin can act as an endogenous modulator of the vascular actions of kinins. ACE inhibition can influence differently the BK-potentiating activity of Ang-(1-7) in normotensive and hypertensive rats.
Angiotensin II Blockade Does Not Prevent Renal Effects of L-NAME in Sodium-Repleted Humans
Authors: Montanari Alberto , Tateo Enrico , Fasoli Elena , Giberti Daniela , Perinotto Patrizia , Novarini Almerico , Dall’Aglio Pierpaolo
Published: June 2012

Abstract
In seven healthy, young subjects on a 240 mmol sodium diet, mean arterial pressure (MAP), renal hemodynamics, and renal handling of Na and exogenous Li were measured at baseline and during short-term nitric oxide (NO) blockade with a 90-minute infusion of 3.0 μg · kg
−1
· min
−1
of
N
G
-
l
-arginine methyl ester (L-NAME). The infusion was performed twice: after a 3-day pretreatment with either placebo or 50 mg losartan to block Ang II receptors. With placebo, L-NAME produced no change in MAP from 0 to 45 minutes (period 1) and only a 5% increase at 45 to 90 minutes (period 2) of infusion. Effective renal plasma flow (ERPF, PAH clearance) and glomerular filtration rate (GFR, inulin clearance) declined by 11.7% and 8.0%, respectively in period 1 and by 14.6% and 11.6%, respectively, in period 2. Calculated renal vascular resistance (RVR) increased by 13.0% to 20.6%. Fractional excretion of Na (FE
Na
) and Li (FE
Li
) fell by 30.0% and 21.0%, respectively, in period 1 and by 44.2% and 31.1% in period 2. All these variations were significant versus baseline. With losartan, the rise in MAP at 45 to 90 minutes was completely abolished, whereas all changes in ERPF, GFR, RVR, FE
Na
, and FE
Li
in response to L-NAME were the same as those observed with placebo. The present data show that NO blockade with low-dose systemic infusion of L-NAME produces renal vasoconstriction, reduced GFR, and increased tubular Na reabsorption independent of changes in MAP. Reduced FE
Li
indicates an effect of NO on the proximal tubule. Since these changes are not prevented by losartan, we conclude that in Na-repleted humans, renal vasoconstriction and Na-retaining effects of inhibition of basal NO production are not due to the unopposed action of endogenous Ang II.
Nitric Oxide Blunts Sympathetic Response of Pregnant Normotensive and Hypertensive Rat Arteries
Authors: Coelho Eduardo B. , Ballejo Gustavo , Salgado Maria Cristina O.
Published: June 2012

Abstract
Rat pregnancy is associated with a blunted response to vasocontrictors both in vivo and in vitro as well as a decrease in arterial pressure. We examined the influence of pregnancy on neurally induced vasoconstrictor and vasodilator responses of the isolated mesenteric arterial bed from normotensive Wistar and spontaneously hypertensive nonpregnant and 20-day pregnant rats and determined the possible role of nitric oxide (NO) in modulating these responses. MAP (mm Hg) in pregnant normotensive (98±1, n=13) and hypertensive (136±5, n=13) rats was lower (
P
<.05) than in nonpregnant controls (114±2, n=14, and 174±3, n=12, respectively). In isolated mesenteric arterial beds, electrical field stimulation (EFS; 34 V, 3 ms, 10-64 Hz) of perivascular nerves at basal tone induced a frequency-dependent increase in perfusion pressure that was significantly (
P
<.001) greater in preparations from hypertensive compared with normotensive rats. Pregnancy was associated with a significant decrease in the maximal vasoconstrictor response elicited by EFS in both normotensive and hypertensive groups compared with their nonpregnant controls. In phenylephrine-preconstricted mesenteric beds, EFS (60 V, 1 ms, 1-8 Hz) elicited a similar frequency-dependent decrease in perfusion pressure in normotensive and hypertensive groups, but pregnancy did not influence these responses. In the presence of the NO synthase inhibitor
N
ω
-nitro-
l
-arginine (200 μmol/L), the maximal vasoconstrictor response induced by EFS was significantly (
P
<.001) augmented in both normotensive and hypertensive groups, and the differences observed between pregnant and nonpregnant groups were abolished. Responses to sodium nitroprusside were not affected by pregnancy, although they were greater in preparations from hypertensive rats. These results indicate that NO contributes to pregnancy-associated diminished vasoconstrictor response to sympathetic stimulation in the mesenteric arterial bed of both normotensive and hypertensive rats.
Circadian Blood Pressure Variability in Healthy and Complicated Pregnancies
Authors: Ayala Diana E. , Hermida Ramón C. , Mojón Artemio , Fernández José R. , Iglesias Manuel
Published: June 2012

Abstract
With the aim to describe the circadian pattern of noninvasive ambulatorily monitored blood pressure during the trimesters of pregnancy in clinically healthy women as well as in pregnant women who developed gestational hypertension or preeclampsia, we analyzed 759 blood pressure series sampled by ambulatory monitoring for about 48 hours every 4 weeks after the first obstetric visit in 71 women with uncomplicated pregnancies, 28 with gestational hypertension, and 14 with preeclampsia. The circadian pattern of blood pressure variation for each group (complicated versus uncomplicated pregnancies) and trimester of gestation was established by linear least-squares methods. A highly statistically circadian pattern is demonstrated for systolic and diastolic blood pressure for both groups of pregnant women in all trimesters (
P
<.001 in all cases). Blood pressure decreases from the first trimester to the second and rises again in the third for healthy pregnant women. For women who developed gestational hypertension or preeclampsia, blood pressure is stable during the first half of pregnancy and then continuously increases until delivery. The differences in circadian rhythm-adjusted mean between complicated and uncomplicated pregnancies are highly statistically significant in all trimesters (always
P
<.001). This study confirms and extends to ambulatory everyday life conditions the predictable circadian variability in blood pressure during gestation. The differences in blood pressure between healthy and complicated pregnancies can be observed as early as the first trimester of pregnancy. Those differences are found when both systolic and diastolic blood pressures for women with a later diagnosis of gestational hypertension or preeclampsia are well within the accepted normal physiological range of blood pressure variability.