bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood pressure control in children of Cordoba, Argentina.
Authors: Bendersky M , Resk J , Kuschnir E , Molina de Illia M , Iglesias L , Aprile E , de Roiter H G , Nigro D
Published: August 2012

The aims of the present study were 1) to evaluate blood pressure (BP) and its distribution curve in a highly representative population of children and adolescents from Cordoba, Argentina, to determine the normal BP pattern, and 2) to establish the relation between other factors and BP levels. BP data recorded during the years 1984-1987 were evaluated in 280,584 children and adolescents aged 5-15 years (52.1% boys and 47.9% girls) corresponding to the nine sanitary districts of the province (urban, rural, mountain, and plains areas), which represent 75% of the children of the whole province. Recordings were carried out by trained physicians who used pediatric BP cuffs and calibrated sphygmomanometers. Korotkoff periods 1 and 5 were considered as the systolic and diastolic BP, respectively. BP was recorded in groups of three to five students with students in a sitting position as part of the routine physical examination and after a thorough explanation of the methodology. For statistical analysis, the Student's t test and stepwise regression analysis were used. Percentile tables and curves were prepared for each age and sex group. Weight and height values were added to the information obtained. Diastolic BP was greater in girls than in boys between the ages of 11 and 14. Systolic BP was lower and diastolic BP was higher in the US Task Force study compared with these findings. Of all the independent variables evaluated, weight influenced BP the most. Age had less influence on BP when height and weight were normalized by regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Differential actions of angiotensin II and angiotensin-(1-7) on transmitter release.
Authors: Diz D I , Pirro N T
Published: August 2012

The central cardiovascular and dipsogenic effects of angiotensin II involve interactions with norepinephrine, dopamine, and serotonin. Our findings that angiotensin II receptors and substance P immunoreactivity show a parallel distribution in the dorsal medulla and that angiotensin II releases substance P from perfused rat medulla slices revealed the potential for a functional relation between these peptidergic systems as well. Additional evidence suggests that the heptapeptide angiotensin-(1-7) exerts its biological activities via selective angiotensin receptor subtypes. Thus, we compared the effects of these two peptides on release of substance P and monoamines in perfused slices of medulla and hypothalamus from 77 male Sprague-Dawley rats. Transmitter levels were determined in 6-minute collections of perfusate before (basal), during (experimental), and after (recovery) perfusion with either angiotensin-(1-7), angiotensin II, or Krebs' solution alone (control). Substance P was measured by radioimmunoassay and monoamines and their metabolites by high-performance liquid chromatography with electrochemical detection. In the medulla, 2 microM angiotensin II but not angiotensin-(1-7) significantly increased efflux of substance P (221 +/- 87% of basal) and norepinephrine (130 +/- 17% of basal) during the experimental period. The effect of angiotensin II on substance P was sustained into the recovery period. Dopamine and its metabolite 3,4-dihydroxyphenylacetic acid were not detected in this brain region. In the hypothalamus, both angiotensin-(1-7) and angiotensin II increased substance P (169 +/- 30% and 141 +/- 35% of basal, respectively); the effect of angiotensin II was sustained throughout the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)
Stimulation of endothelial cell prostaglandin production by angiotensin peptides. Characterization of receptors.
Authors: Jaiswal N , Diz D I , Chappell M C , Khosla M C , Ferrario C M
Published: August 2012

Angiotensin II stimulates prostaglandin release in blood vessels via activation of angiotensin receptors present in endothelium, vascular smooth muscle cells, or both. We evaluated the response of angiotensin II, angiotensin I, and [des-Phe8] angiotensin II [angiotensin-(1-7)] on prostaglandin release in porcine aortic endothelial cells. Incubation of cell monolayers with angiotensin I and angiotensin-(1-7), but not angiotensin II, stimulated the release of prostaglandin E2 and prostaglandin I2 in a dose-dependent manner (10(-10) to 10(-6) M) with an EC50 of approximately 1 nM. In addition, we characterized the angiotensin receptor subtypes mediating prostaglandin synthesis by using subtype-selective antagonists. Angiotensin I-stimulated prostaglandin synthesis was not altered by either of the nonselective classical angiotensin receptor antagonists [Sar1,Thr8]angiotensin II or [Sar1,Ile8]angiotensin II. In contrast, either the angiotensin subtype 1 (AT1) antagonist DuP 753 or the subtype 2 (AT2) antagonist CGP42112A significantly attenuated the prostaglandin release in response to angiotensin I. However, PD123177, another AT2 antagonist, did not inhibit angiotensin I-stimulated prostaglandin release. Angiotensin-(1-7)-induced prostaglandin release was significantly attenuated by [Sar1,Thr8]angiotensin II (10(-6) M) and PD123177 (10(-6) M) but not by [Sar1,Ile8]angiotensin II, DuP 753, or CGP42112A. Higher doses (10(-5) M) of DuP 753 and CGP42112A attenuated the angiotensin-(1-7) response. These data suggest that in porcine aortic endothelial cells, angiotensin I and angiotensin-(1-7) but not angiotensin II are potent stimuli for prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of protein kinase C and calcium on bradykinin-mediated contractions of rabbit vessels.
Authors: Calixto J B , Medeiros Y S
Published: August 2012

Bradykinin caused graded contractions of rings of rabbit aorta and jugular vein with EC50 values of 1.3 microM and 2.2 nM. In denuded preparations, responses of bradykinin in jugular vein but not in aorta were potentiated 1,000-fold. Both preparations bathed in calcium-free solution showed markedly depressed responses to bradykinin, but addition of 1 mM EGTA further inhibited bradykinin responses only in aorta. Time-course experiments carried out in calcium-free solution plus EGTA revealed that bradykinin contractions in rabbit aorta were very sensitive to extracellular calcium, whereas responses of the jugular vein depended on both extracellular and intracellular calcium sources. Responses to bradykinin in both tissues were unaffected by nicardipine (1 microM) but were partially antagonized by NiCl2 (0.1-0.3 mM). Ryanodine (30 microM) incubated in calcium-free medium markedly inhibited jugular vein responses to bradykinin but had no effect on aortic responses. Phorbol ester (1 microM) caused a slow tonic contraction in jugular vein but not in aorta and inhibited bradykinin responses in the former preparation. Staurosporine (1-100 nM) and 1-(5-isoquinolinesulfonyl)-2-methylpiperizine (H-7, 3 and 10 microM) caused a dose-dependent inhibition of bradykinin-induced contractions in jugular vein but were less effective in aorta.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of 1 M NaCl cerebroventricular injection on renal and baroreceptor reflex functions.
Authors: Vidal N A , Isola M C , Mones Sías M C , Balaszczuk A M , Majowicz M P , Gonzalez D , Arranz C T
Published: August 2012

Our purpose was to study the influence of the stimulation of the cerebroventricular system on some mechanisms related to hydrosaline equilibrium and blood pressure regulation. Renal function and blood pressure (group 1) as well as the baroreceptor reflex (group 2) were studied. In group 1, we measured diuresis, natriuresis, creatinine clearance, lithium clearance, and blood pressure in control rats and after stimulation of the cerebroventricular system with 1 M NaCl solution. In group 2, we evaluated the baroreceptor reflex, producing an increase of blood pressure with an injection of phenylephrine to obtain baroreceptor reflex curves--characterized by threshold, point of inflection, heart period range, gain, and systolic pressure corresponding to half the heart period range (SBP50)--in control and experimental rats injected with saline and 1 M NaCl solution, respectively. In group 1 experimental rats, we observed a significant increase in diuresis, natriuresis, blood pressure, and glomerular filtration rate. A substantial increase was also registered in sodium filtered load and reabsorbed sodium in the proximal convoluted tubule and distal nephron. No differences were observed either in fractional proximal tubule or in distal nephron sodium reabsorption. In group 2 experimental rats, mean arterial blood pressure, threshold, point of inflection, and SBP50 were significantly higher than in control rats. By contrast, a decrease in gain and heart period range was observed. No difference was obtained in heart rate. Our results demonstrate that the increase of the natriuresis is due, at least in part, to an increase in sodium filtered load.(ABSTRACT TRUNCATED AT 250 WORDS)
Time course study of blood pressure in children over a three-year period. Bogalusa Heart Study.
Authors: Voors A W , Webber L S , Berenson G S
Published: August 2012

Indirect blood pressure (BP) was measured by mercury sphygmomanometer on 3524 children, ages 5-14 years, representative of a defined geographic population. Year 1 to Year 4 correlations ranged from 0.52 to 0.63 systolic blood pressure (SBP) and from 0.23 to 0.45 diastolic 4th phase blood pressure (DBP4). Some 55% of those originally in the upper decile remained in the uppermost two deciles 3 years later. All children ages 5, 8, 11, and 14 years were reexamined annually, and the mean year-to-year standard deviation (SD) within the child was computed to be 5.5 mm Hg SBP and 5.9 mm Hg DBP. After 3 years, for all available children (n = 2601) the age-specific cross-sectional SD was found to be 8.7-9.7 mm Hg SBP and 7.6-8.0 mm Hg DBP. These data enabled us to quantify the regression to the mean due to within-child variation for the uppermost and the lowest decile BP, using the Gardner-Heady model. These children had an average BP at examination that differed from the expected level (adjusting for regression to the mean due to within-child variation) by 1 mm Hg SBP and DBP. Quantification of the degree to which children's BP "tracks" is important for early diagnosis and intervention in high BP.
Blood pressure in infant twins: birth to 6 months of age.
Authors: Levine R S , Hennekens C H , Duncan R C , Robertson E G , Gourley J E , Cassady J C , Gelband H
Published: August 2012

To describe the time course of the early development genetic variance for blood pressure, a cohort of twins is being followed from birth to 1 year of age. The present interim report describes systolic and diastolic blood pressure measurements for 102 twin pairs (39 monozygotic (MZ) and 63 dizygotic (DZ) in the newborn period and at 1, 3 and 6 months of age. Mean values for both systolic and diastolic blood pressure were similar regardless of race, sex, zygosity, or chorionicity. Statistically significant genetic variance was detected for systolic blood pressure at 6 months of age but not for diastolic blood pressure at any data point. The data are consistent with the hypothesis that genetic factors that determine within-family similarities of blood pressure may be detected early in life, and support the need for further investigation of both genetic and environmental determinants of blood pressure in young populations.
An approach to the evaluation of genetic influences on factors that regulate arterial blood pressure in man.
Authors: Grim C e , Luft F C , Miller J Z , Rose R J , Christian J C , Weinberger M H
Published: August 2012

To assess the influence of heredity on factors that help regulate the arterial blood pressure in man, we conducted sodium-loading and depletion studies in monozygotic and dizygotic twins, normotensive first-degree relatives of essential hypertensives, and in normotensive control subjects matched for age, sex, and race. Following sodium-loading, we found evidence for the influence of genetic variance on the natriuretic responses, plasma renin activity (PRA), plasma aldosterone concentrations (PA), and plasma and urinary norepinephrine. Relatives of hypertensives differed from controls in that they had higher blood pressures, greater renin values, and relatively sluggish natriuretic responses. Since renin and fractional sodium excretion values were inversely correlated in all subject groups, it is possible that the heritable influences we observed on sodium excretion were mediated by the renin-angiotensin-aldosterone system.
Blood pressure, growth and maturation from childhood through adolescence. Mixed longitudinal analyses of the Philadelphia Blood Pressure Project.
Authors: Katz S H , Hediger M L , Schall J I , Bowers E J , Barker W F , Aurand S , Eveleth P B , Gruskin A B , Parks J S
Published: August 2012

This paper presents data on the extent to which blood pressure (BP) and growth status at 7 years of age are associated with BP, growth, and maturity status during adolescence. Two samples of black adolescents, namely, a representative sample (n = 562) stratified by sex and age (11 to 15 years) and a sample (n = 256) with supine BP over one standard deviation above the mean at 7 years of age (High BP7), were selected from the Philadelphia Collaborative Perinatal Project (CPP) population and followed longitudinally for 3 years. When the subjects reached adolescence we again measured supine blood pressure, height, weight, and skeletal maturity. Analyses of the data collected at 7 years of age by the CPP indicated that weight and height are highly significantly associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) respectively. Accordingly, the SBP, DBP, weights, and heights of the representative sample at age 7 were divided into percentile groupings (< 15%, 15%-85%, > 85%). Using mixed longitudinal analyses during adolescence, we found that mean SBP tracked in males through age 15 and in females through age 13 based on the percentile groupings of SBP, height, and weight. Moreover, the weight percentile groupings provided the best discrimination of SBP at these ages. Skeletal age also tracked throughout early adolescence using these percentile groupings of 7-year heights and weights. In females only, diastolic phase 4 (DBP4) during adolescence was significantly associated with 7-year height percentile groupings. In comparing the representative and the High BP7 samples at each chronological age for BP, height, weight, and skeletal age at adolescence (ages 12 to 17 years), it was found that the High BP7 sample was, on the average, taller and heavier at age 7 and throughout early adolescence. At age 17 in males, however, there were no significant differences in BP, growth, or maturity status. In females, SBP of the High BP7 sample remained significantly higher, and there was a tendency for them to remain heavier through age 17. Hence BP variation is so closely associated with growth and maturation that these factors must be taken into account when assessing BP in childhood and adolescence.
Modulation of renin-angiotensin and kallikrein gene expression in experimental hypertension.
Authors: Von Thun A M , el-Dahr S S , Vari R C , Navar L G
Published: August 2012

Previous studies have shown that chronic low-dose administration of 40 ng/min angiotensin II by osmotic minipump to uninephrectomized rats mimics the temporal hypertensive response and the circulating angiotensin II levels observed in two-kidney, one clip Goldblatt rats. Furthermore, renal tissue angiotensin II contents were higher than the circulating angiotensin II levels, suggesting that circulating angiotensin II induces endogenous intrarenal angiotensin II production. The present study examined the molecular mechanisms by which intrarenal angiotensin II production is modulated in angiotensin II-induced and two-kidney Goldblatt hypertension. Two weeks after clipping, intrarenal renin mRNA levels were elevated threefold in the clipped kidney of Goldblatt rats but were markedly suppressed in the nonclipped kidneys of Goldblatt rats (28% of control values) and in the remaining kidney of uninephrectomized angiotensin II-infused rats (7% of control values). In contrast, there were sustained levels of angiotensinogen mRNA in the kidneys and livers of Goldblatt and angiotensin II-infused rats, indicating differential regulation of the genes of the renin-angiotensin system. Renal kallikrein gene expression was not altered in either of the hypertensive groups 14 days after the induction of hypertension, suggesting the absence of an enhanced counteracting kinin influence.
Biochemical evidence of a kallikrein-like activity in rat reproductive tissues.
Authors: Miatello R , Lama M , González S , Damiani T , Nolly H
Published: August 2012

We performed this study to examine the presence of a kallikrein-kinin system in rat fetal and maternal tissues. Uteri and placenta from Wistar pregnant and nonpregnant rats were perfused to eliminate blood, and fetal membranes were washed several times with saline. Amniotic fluids were obtained without blood contamination by amniocentesis from eight rats. The different samples were homogenized and centrifuged (2000g during 20 minutes), and the supernatant was incubated with dog kininogen and 0.1 mol/L Tris-HCl buffer (pH 8.5) in the presence of peptidase inhibitors. Kinins released were measured by radioimmunoassay. Kininogenase activity was found in rat uteri, placental vessels, amniotic fluids, and fetal membranes. The enzymes were present in active but mostly in inactive forms. The kallikrein-like enzymes found in the different preparations and rat urinary kallikrein used as control had similar molecular weights, immunologic characteristics, and inhibition profiles with protease inhibitors. We conclude that kallikrein-like enzymes are present in rat organs of reproduction. These data suggest that kinins released locally may act as paracrine hormones in the regulation of blood pressure during pregnancy.
Insulin attenuates agonist-evoked calcium transients in vascular smooth muscle cells.
Authors: Touyz R M , Tolloczko B , Schiffrin E L
Published: August 2012

Insulin may decrease the contractile response of vascular smooth muscle to vasoactive agents. This could be due to interactions of insulin with the effects of vasoactive agonists on intracellular free calcium transients in vascular smooth muscle cells. This study assesses the effects of physiological doses of insulin (70 microU/mL) on calcium responses in cultured vascular smooth muscle cells (primary unpassaged and passaged) to angiotensin II (1 nmol/L), arginine vasopressin (10 nmol/L), and norepinephrine (10 mumol/L). Intracellular free Ca2+ concentrations in single cells were measured microphotometrically using fura 2-AM. Insulin, angiotensin II, arginine vasopressin, and norepinephrine significantly increased calcium (to 115 +/- 7, 183 +/- 20, 184 +/- 15, and 168 +/- 12 nmol/L, respectively, from basal calcium of 90 +/- 10 nmol/L). Insulin significantly attenuated the agonist-induced calcium responses. The effects of insulin were almost completely inhibited by diltiazem, staurosporine, calphostin C, and thapsigargin. In conclusion, insulin stimulates calcium transients but blunts agonist-mediated calcium rises in vascular smooth muscle cells. These responses are related to regulatory effects of insulin on cellular calcium homeostasis and may explain how insulin modulates vascular smooth muscle contraction.
Nitric oxide influences blood flow distribution in renovascular hypertension.
Authors: Sigmon D H , Beierwaltes W H
Published: August 2012

Endothelium-derived nitric oxide contributes to the regulation of regional blood flow. Inhibition of endothelium-derived nitric oxide synthesis increases blood pressure and vascular resistance. Using the substrate antagonist N omega-nitro-L-arginine-methyl ester to block endothelium-derived nitric oxide synthesis, we tested the hypothesis that, in two-kidney, one clip renovascular hypertension, endothelium-derived nitric oxide plays an increased role in maintaining blood flow to the nonclipped kidney and other visceral organs compared with normotensive controls. This could be due to increased vascular shear stress, a primary stimulus for endothelium-derived nitric oxide synthesis, after the onset of hypertension. In hypertensive rats with mild renal artery stenosis, basal renal blood flow normalized by kidney weight was similar in the nonclipped and clipped kidneys. Basal blood pressure of controls was 98 +/- 2 mm Hg compared with 145 +/- 3 mm Hg in the two-kidney, one clip hypertensive rats. N omega-nitro-L-arginine-methyl ester increased blood pressure by 20 +/- 2 and 43 +/- 3 mm Hg in control and hypertensive rats, respectively. Compared with normotensive controls, basal resistance was higher in all organ beds in the hypertensive rats including brain, heart, intestine, and kidney. With the exception of the renal circulation, the increase in vascular resistance after N omega-nitro-L-arginine-methyl ester was greater in hypertensive rats compared with normotensive controls. In the hypertensive rats, N omega-nitro-L-arginine-methyl ester caused a similar increase in vascular resistance in both the nonclipped and clipped kidneys, and this was not different from normotensive controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Abnormal pressure natriuresis in the dog model of obesity-induced hypertension.
Authors: Granger J P , West D , Scott J
Published: August 2012

Obesity is considered to be a major factor in the pathogenesis of hypertension in industrialized countries. Recent studies have suggested that the kidneys may play an important role in the development of obesity-induced hypertension. The purpose of this study was to determine whether obesity-induced hypertension is associated with abnormalities in the pressure-natriuresis relation. Renal function studies were performed in anesthetized control dogs (body weight, 20.2 +/- 0.8 kg) and obese dogs (body weight, 26.4 +/- 0.7 kg) that were maintained on a high-fat diet for 5 to 6 weeks. Mean arterial pressure averaged 122 +/- 5 mm Hg in the control group (n = 6) and 148 +/- 7 mm Hg in the obese group (n = 8). The effects of renal perfusion pressure on renal hemodynamics as well as sodium and water excretions were examined at five levels of renal perfusion pressure ranging from 75 to 165 mm Hg. Pressure-natriuretic and diuretic responses were reduced in the obese dogs by 40% to 50%. The renal blood flow and glomerular filtration rate autoregulatory responses and fractional lithium excretion responses to changes in renal perfusion pressure were similar in the control and obese dog groups. Associated with the attenuated natriuretic response to renal perfusion pressure in the obese dogs were significant elevations in plasma renin activity (4.3 +/- 1.6 versus 1.6 +/- 0.5 ng angiotensin I/mL per hour), plasma aldosterone concentration (34.4 +/- 6.4 versus 15.3 +/- 3.2 ng/dL), and plasma insulin concentration (30.5 +/- 6.8 versus 20.9 +/- 2.9 IU/mL).(ABSTRACT TRUNCATED AT 250 WORDS)
Neural effects on renal blood flow during acute hypotension vary with antihypertensive drugs.
Authors: Takishita S , Muratani H , Kawazoe N , Kimura Y , Tozawa M , Fukiyama K
Published: August 2012

To examine the neural effects of antihypertensive drugs on renal blood flow, we measured blood flow and renal sympathetic nerve activity simultaneously in conscious spontaneously hypertensive rats aged 13 to 15 weeks. One to two days after surgery, intravenous administration of manidipine (calcium antagonist, n = 10), doxazosin (alpha 1-adrenergic receptor antagonist, n = 9), and clonidine (n = 7) lowered mean arterial pressure by at least 20% from baseline levels. Manidipine initiated a reduction of renal blood flow when mean pressure decreased by 20 +/- 2 mm Hg. At the maximal decrease in renal blood flow (mean pressure, -33 +/- 2 mm Hg), percent decrease in flow (-27 +/- 2%) significantly correlated with percent increase in renal nerve activity (+205 +/- 40%, r = -.878). Doxazosin began to decrease renal blood flow at a level of arterial pressure similar to that in manidipine treatment, whereas the maximal decrease in flow (-19 +/- 2%; mean pressure, -33 +/- 2 mm Hg; nerve activity, +225 +/- 44%) was significantly less than that in manidipine treatment. Although clonidine decreased arterial pressure and renal nerve activity, renal blood flow did not decrease even at the maximal decrease in mean pressure of 29 +/- 1 mm Hg. The addition of clonidine to manidipine treatment suppressed reflexly enhanced renal nerve activity and restored blood flow to the pretreatment level despite pronounced hypotension. These results clearly demonstrate that antihypertensive drugs with blocking action on renal nerve activity are capable of maintaining renal blood flow and that those associated with reflex-induced enhancement of nerve activity exert deteriorating effects on renal blood flow. Furthermore, a decrease in renal blood flow induced by calcium antagonists is mainly attributed to reflexly enhanced renal nerve activity.
Blood pressure regulation in pheochromocytoma.
Authors: Bravo E L , Tarazi R C , Fouad F M , Textor S C , Gifford R W , Vidt D G
Published: August 2012

Two sets of studies were performed in 13 patients with proved adrenal pheochromocytoma to test the hypothesis that the sympathetic nervous system (SNS) is active and might contribute to the hypertensive state. Similar studies were performed in 15 additional patients considered to have essential hypertension. In the first set, 13 patients with pheochromocytoma were subjected to head-up tilt to assess the activity of the SNS. This maneuver decreased diastolic blood pressure in only two; heart rate increased appropriately in all except one. Changes in plasma norepinephrine (NE) were variable and did not correlate with changes in blood pressure (BP) and heart rate (HR). In the second set, 10 patients with pheochromocytoma were given a single oral dose of clonidine (0.3 mg) to evaluate what role, if any, the SNS might contribute to the hypertensive state. Fifteen patients with essential hypertension were studied similarly for comparison. Clonidine produced significant decreases in BP and HR but left plasma renin activity unchanged in both groups. In essential hypertension, the cardiovascular responses were accompanied by significant reductions in plasma NE. By contrast, plasma NE was unchanged in patients with pheochromocytoma, despite similar reductions in BP and HR. These results suggest that the sympathetic reflexes are intact in pheochromocytoma, and that much of the hypertension associated with these tumors may be related to increased sympathetic activity.
Aspects of angiotensin action in the adrenal. Key roles for calcium and phosphatidyl inositol.
Authors: Elliott M E , Alexander R C , Goodfriend T L
Published: August 2012

The steps between exposure of bovine adrenal glomerulosa cells to angiotensin and the stimulated increase in aldosterone production were studied in two ways. Binding of angiotensin to receptors, and hormone effects on phosphatidyl inositol turnover, 45Ca2+ fluxes, and aldosterone production were measured directly. Other potential intermediate steps were investigated indirectly by use of inhibitors. Angiotensin slowed calcium influx and accelerated phosphatidyl inositol turnover in proportion to hormone dose. The effects correlated with receptor binding and aldosterone production. None of the inhibitors tested, except saralasin, inhibited angiotensin's effect on phosphatidyl inositol turnover. Altered calcium flux and stimulated aldosterone production were affected by the calmodulin inhibitor trifluoperazine and the intracellular calcium antagonist 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8). Several reagents did not affect angiotensin binding, its effect on phosphatidyl inositol, or 45Ca2+ flux, but severely inhibited steroidogenesis. These included the phospholipase A2 inhibitor mepacrine, the protein synthesis inhibitor cycloheximide, and the Na+/k+-ATPase inhibitor ouabain. Colchicine had very little effect on the processes we measured, suggesting that microtubules play no role in angiotensin action in the adrenal. Based o these observations, we propose that angiotensin II affects the adrenal glomerulosa cell by first interacting with receptors, then increasing phosphatidyl inositol turnover, then altering cellular calcium distribution. Step distal to altered calcium distribution that contribute to increased steroid output include altered phospholipid metabolism, protein synthesis, and Na/k metabolism.
Saralasin dilates arterioles in SHR but not WKY rats.
Authors: Longnecker D E , Durieux M E , Donovan K R , Miller E D , Peach M J
Published: August 2012

Microvascular responses to topical or intravascular saralasin were determined in the cremaster muscle arterioles of adult spontaneously hypertensive rats (SHR, n = 19) and Wistar-Kyoto (WKY, n = 16) normotensive rats. Animals were anesthetized with chloralose and urethane, and they breathed room air spontaneously. Mean arterial pressure was obtained from a catheter in a carotid artery, and microvascular diameters were determined by video microscopy. Plasma renin activity was measured in animals that were treated identically except that saralasin was not administered. For all animals, mean arterial pressure averaged 126 +/- 4 mm Hg in SHR and 82 +/- 4 mm Hg (p less than 0.001) in WKY rats. Topical saralasin, 10(-6)M, was applied to the cremaster muscles of SHR (n = 9) or WKY (n = 8) rats while internal diameters of first-through fourth-order arterioles (A1, A2, A3, A4) were measured. Topical saralasin did not alter arteriolar diameters (A1 through A4) in WKY rats, but A3 and A4 vessels dilated significantly (29% +/- 5% and 38% +/- 7% respectively; p less than 0.01) in SHR. Fourth-order diameters were measured in other SHR (n = 10) and WKY (n = 8) rats while saralasin was administered intraarterially (300 micrograms bolus into the hypogastric artery) or intravenously (10 micrograms/kg/min for 30 minutes). Intraarterial or intravenous saralasin caused significant dilation (32% +/- 12% and 20% +/- 4%, respectively; p less than 0.01) of A4 arterioles in SHR, but no dilation occurred in the arterioles of WKY rats. Arteriolar responses were significantly different (p less than 0.001) in SHR vs WKY rats for both the topical and the intravascular administration of saralasin.(ABSTRACT TRUNCATED AT 250 WORDS)
Statine-containing renin inhibitor. Dissociation of blood pressure lowering and renin inhibition in sodium-deficient dogs.
Authors: Blaine E H , Schorn T W , Boger J
Published: August 2012

Iva-His-Pro-Phe-His-Sta-Leu-Phe-NH2 is a new, potent, specific statine -containing renin inhibitor. In vitro, the ID50 needed to inhibit both dog and human plasma renin is approximately 10(-8)M. Injections into anesthetized rats receiving a continuous intravenous infusion of hog renin revealed a dose-related lowering of mean arterial blood pressure (MAP) with an ID50 of 0.04 mg/kg. In conscious Na-deficient dogs, infusion of the inhibitor for 48 hours resulted in a sustained lowering of MAP and suppression of plasma renin activity (PRA). To study the relationship between MAP lowering and inhibition of PRA, conscious Na-deficient dogs received continuous intravenous infusions for 1 to 3 hours. At doses of 20, 40, and 160 micrograms/kg X min, MAP was reduced 9 +/- 3, 15 +/- 0, and 22 +/- 4 mm Hg. No dose-related response was observed for PRA, which decreased from 7.8 +/- 0.9 to 0.4 +/- 0.3, 0.1 +/- 0.1, and 0.4 +/- 0.2 ng angiotensin I/ml X hr, respectively. Further studies using much-reduced infusion rates revealed a dose-related inhibition of PRA but not MAP. Doses of 0.1, 0.2, and 1.0 micrograms/kg X min inhibited PRA, 34% +/- 1%, 52% +/- 3%, and 82% +/- 4% while MAP decreased, 3 +/- 1, 4 +/- 1, and 2 +/- 1 mm Hg, respectively. These data reveal the potent blood-pressure-lowering effects of this new renin inhibitor and suggest that there may not be a direct relationship between inhibition of circulating renin and blood pressure lowering in Na-deficient dogs.
Effect of changes in sodium or potassium balance, and nephrectomy, on adrenal renin and aldosterone concentrations.
Authors: Doi Y , Atarashi K , Franco-Saenz R , Mulrow P J
Published: August 2012

An active form of renin was confirmed in the adrenal gland of rats. It had a molecular weight of 40,000, generated angiotensin I (AI) from natural renin substrate at pH 7.4, and was found at concentrations 30 to 60 times higher than plasma renin in rats on a normal diet. Changes in sodium diet induced changes in adrenal capsular renin concentration (high Na 2.21 +/- 0.34, normal Na 4.34 +/- 0.53, low Na 13.19 +/- 1.67 ng AI/mg protein/hr). A high potassium diet also increased adrenal capsular renin from 5.27 +/- 0.53 to 39.78 +/- 5.68 ng AI/mg protein/hr, while plasma renin concentration decreased from 7.28 +/- 0.63 in the normal diet to 5.05 +/- 0.60 on the high potassium diet. Neither diet altered the concentration of renin in the fasciculata-medullary portion of the adrenal gland. Nephrectomy markedly increased the renin concentration in the adrenal capsules without any effect on the decapsular cells (20 hours after nephrectomy, 71.5 +/- 10.6 ng AI/mg protein/hr). Sodium loading or dexamethasone treatment prior to nephrectomy blunted the rise in adrenal renin (nephrectomy + dexamethasone = 27.64 +/- 4.33 ng AI/mg protein/hr; nephrectomy + NaCl = 38.70 +/- 5.82 ng AI/mg protein/hr). In all experiments, there was a positive correlation between adrenal renin and adrenal aldosterone concentrations, but the experiments did not rule out the possibility that this positive correlation was due to two independent variables changing in the same direction and not causally related. In conclusion, adrenal renin may be a local hormone, involved in the regulation of aldosterone production.
Distribution of immunoreactive angiotensin II, angiotensin I, angiotensinogen and renin in the central nervous system of intact and nephrectomized rats.
Authors: Healy D P , Printz M P
Published: August 2012

Evidence for an intracellular pathway for angiotensin synthesis in the central nervous system (CNS) was examined using immunohistochemistry to compare the distribution of angiotensin I (AI), AII, angiotensinogen, and renin in the hypothalamic paraventricular nuclei (PVN) and supraoptic nuclei (SON), median eminence (ME), and pituitary gland in intact and nephrectomized rats. In intact rats injected intracerebroventricularly (i.c.v.) with colchicine, AII neurons were found in the parvocellular PVN, and terminals were seen in the external lamina of the ME. In the pituitary gland, AII was localized within cells of the anterior and intermediate lobes, whereas the posterior pituitary was unstained. In contrast, 24 to 48 hours following nephrectomy, AII-labeled neurons were observed in the magnocellular PVN and SON, even without the aid of i.c.v. colchicine. Likewise, axons within the internal layer of the ME were now labeled, but the pituitary was completely devoid of staining except for the intermediate lobe. AI-labeled neurons were observed only in the parvocellular PVN. Angiotensinogen was localized in the mediobasal hypothalamus, but the PVN and SON were not labeled. Immunoreactive renin was localized within the magnocellular PVN, SON, and posterior lobe of the pituitary in nephrectomized and intact animals. Because of the close overlap of AI and AII staining, these results suggest that AI and AII could represent a precursor product relationship in the CNS. In contrast, in the intact animals, renin and angiotensinogen do not appear to be associated with AII. However, a possible relationship between AII and renin may exist in the magnocellular PVN and SON, since labeled neurons were seen in these nuclei following nephrectomy.
Role of renal hemodynamics and arterial pressure in aldosterone "escape".
Authors: Hall J E , Granger J P , Smith M J , Premen A J
Published: August 2012

This study examined the importance of changes in renal hemodynamics and renal artery pressure (RAP) in allowing the kidneys to escape from the chronic sodium-retaining effects of aldosterone (Aldo). In five dogs in which RAP was permitted to increase during Aldo infusion (14 micrograms/kg/day), sodium excretion (UNaV) and fractional sodium excretion (FENa) decreased markedly on Day 1 and then returned to control on Days 2 to 4 of Aldo infusion as RAP and glomerular filtration rate (GFR) increased 15 to 19 mm Hg and 20% to 24%, respectively, and remained near these levels during 7 days of Aldo infusion. In seven dogs in which RAP was prevented from increasing with an electronically servo-controlled aortic occluder, UNaV decreased from 256 +/- 3 to 117 +/- 9 mEq/day on the first day and remained at 70 to 80 mEq/day below sodium intake for 7 days of Aldo infusion. Cumulative sodium balance and sodium iothalamate space increased 610 +/- 39 mEq and 3729 +/- 397 ml when RAP was servo-controlled, causing ascites in most of the dogs, while mean arterial pressure did not plateau but continued to rise to 59 +/- 3 mm Hg above control after 7 days of Aldo infusion. When the servo-controller was stopped and RAP was allowed to rise while Aldo infusion was continued, GFR rose to 126% to 136% of control, FENa increased markedly, UNaV increased to 579 +/- 64 mEq/day on the first day, and the dogs returned to normal sodium balance. These data indicate that an increase in RAP, which raises GFR and FENa, is essential in allowing the kidneys to escape from the chronic sodium-retaining action of Aldo and to achieve sodium balance and a stable level of arterial pressure without severe volume expansion and ascites.
Mechanism of deterioration in renal function in patients with renovascular hypertension treated with enalapril.
Authors: Bender W , La France N , Walker W G
Published: August 2012

Azotemia produced by converting enzyme inhibition in renovascular hypertension was studied in six patients by measurement of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Patients with unilateral renovascular hypertension lowered GFR acutely to 40% of control values at 4 hours, but after 4 days it only returned to 75% of control even though ERPF exceeded control values. Calculated filtration fraction (GFR/ERPF) decreased from 0.31 to 0.19 in 4 hours (p less than 0.05) and remained at 0.20 after 4 days of treatment despite increases in GFR and ERPF. In bilateral renovascular hypertension, neither the decreased GFR nor lowered ERPF induced by enalapril showed any tendency to return toward normal with continued treatment. These data are consistent with selective glomerular efferent arteriolar dilation in response to enalapril and suggest that angiotensin converting-enzyme inhibition interferes with the autoregulatory capacity of the kidney in the presence of severe renovascular hypertension.
Smooth muscle proliferation in hypertension. State-of-the-art lecture.
Authors: Schwartz S M
Published: August 2012

Similar pathologic changes in atherosclerosis and hypertension suggest that some common mechanisms may underlie these two major vascular diseases. Both diseases are characterized by smooth muscle proliferation. The atherosclerotic lesion is characterized by proliferation of smooth muscle cells in the arterial intima of large arteries, leading to vascular occlusion, lipid accumulation, and thrombosis. Smooth muscle proliferation in hypertensive vascular disease again results in increased wall mass and a narrowed lumen. The small vessel change is though to be etiologic of the increased peripheral resistance of high blood pressure. At least in large vessels, the form of proliferation is quite different. Atherosclerosis shows a true cell proliferation. In contrast, smooth muscle cells from animals with hypertensive vascular disease show DNA replication without mitosis. The resulting endoreplication is suggestive of the forms of replication seen in differentiated sarcomeric muscle, particularly in cardiac myocytes.
Outcomes to middle cerebral artery occlusion in hypertensive and normotensive rats.
Authors: Coyle P
Published: August 2012

To ascertain whether infarction and noninfarction outcomes to rapid occlusion of the middle cerebral artery (MCA) are differentiated by alteration of the systolic blood pressure (BP), rats under the following conditions were tested: normal Wistar rats (NW) made acutely hypertensive with deoxycorticosterone acetate (DOCA)-salt, spontaneously hypertensive stroke-prone rats (SHRSP) receiving captopril antihypertensive medication for 7 weeks, and SHRSP with captopril withdrawn 2 weeks prior to the occlusion test. Eleven of 13 acutely DOCA-salt hypertensive NW were protected from infarction. Adequate collateral circulation was preserved in NW vessels initially formed under normotensive conditions but tested during acute DOCA-salt hypertension. Since all SHRSP tested had infarcts, SHRSP were more susceptible to infarction than NW made acutely DOCA-salt hypertensive. SHRSP with captopril medication withdrawn for 2 weeks had higher BP and larger infarcts than SHRSP maintained on the drug. Results suggest that the mechanism causing elevated BP or one secondary to it adversely alters the collateral supply in SHRSP. An increase in collateral vascular resistance initiated during anatomical development of the anastomoses very early in life may predispose SHRSP to infarct after rapid MCA occlusion later in life.
Regression of cardiovascular structural changes by antihypertensive treatment. Functional consequences and time course of reversal as judged from clinical studies.
Authors: Trimarco B , Wikstrand J
Published: August 2012

Echocardiographic studies have shown a decrease in left ventricular (LV) wall thickness and an improvement in LV function during antihypertensive treatment. A reduction in LV mass parallels the reduction in LV wall thickness during the first year of antihypertensive treatment, but thereafter favorable changes in LV wall thickness, cardiac output, and total peripheral resistance may be recorded in spite of a constant LV mass. The reason for this is that LV mass is defined by LV wall thickness and LV end-diastolic diameter, and that LV mass may stay unchanged if LV wall thickness decreases when LV diameter increases. This pattern of change is to be expected since LV distensibility and, hence, LV end-diastolic diameter may increase when LV wall thickness decreases. The effect of treatment may thus be divided into two main phases--an initial phase with a reduction in LV mass and a reduction in cardiac output and no change in total peripheral resistance--and a second phase with a constant LV mass but an increase in cardiac output to the pretreatment level again and a concomitant decrease in total peripheral resistance. The increase in stroke volume and cardiac output during this second phase of treatment is mainly dependent on an increase in end-diastolic volume, most likely explained by improved LV compliance when LV wall thickness decreases. The concomitant decrease in total peripheral resistance is mainly explained by reversal of structural vascular changes.(ABSTRACT TRUNCATED AT 250 WORDS)
Structural changes in resistance and capacitance vessels in borderline hypertension.
Authors: Mark A L
Published: August 2012

Vascular resistance at rest may be normal in humans with borderline or mild hypertension. However, this finding is a facade which can obscure the presence of vascular structural alterations that may have an important influence on resistance and capacitance functions of the circulation. This paper reviews several studies regarding vascular structural changes in borderline hypertension (BHT). First, forearm vasodilator capacity is limited in BHT and in normotensive young men with a family history of hypertension; this suggests the presence of structural changes in forearm resistance vessels. Second, forearm venous distensibility is decreased in BHT. Most of this decrease is caused by nonadrenergic mechanisms--which suggests that there may be structural changes in veins in BHT. Third, the studies of Takeshita and colleagues suggest that sodium intake may influence vascular structural changes. In hypertensive patients who responded to salt loading with increased blood pressure and vascular resistance, salt loading limited vasodilator responses to 10 minutes of ischemia. This effect of salt loading on vasodilator responses occurred in some patients (salt-responders), but not in others (salt-nonresponders). Functional studies support the concept that structural changes in resistance and capacitance vessels occur during the early stages of human hypertension. These changes may not be entirely adaptive responses to elevated arterial pressure, since they occur in capacitance as well as resistance vessels. In addition, the structural changes appear to be responsive to factors such as sodium intake. These observations suggest that vascular structural changes in human hypertension may be related in part to neurohumoral influences or to primary vascular abnormalities.
The coronary circulation in hypertensive heart disease.
Authors: Strauer B E
Published: August 2012

This study analyzes and compares systemic and coronary hemodynamics in patients with essential hypertension in relation to hypertrophic heart disease of nonhypertensive origin. Left ventricular function (as assessed from the cardiac index, stroke volume index, ejection fraction, mean velocity of circumferential fiber shortening, mean normalized systolic ejection rate, and isovolumic indexes) may be normal in patients with hypertensive hypertrophy, even with a large increase in muscle mass and in the presence of concomitant coronary artery disease. Left ventricular function is impaired when regional contraction abnormalities or ventricular dilatation, or both, occur and is inversely related to both cardiac size and systolic wall stress. Coronary blood flow (+ 18%), coronary resistance (+ 38%), and myocardial oxygen consumption (MVO2) (+ 21%) are increased in essential hypertension. Coronary reserve is reduced even in hypertensive hypertrophy without evidence of coronary artery disease. MVO2 per mass unit was directly correlated with systolic wall stress per cross-sectional area of the left ventricular wall. Coronary reserve may remain normal in both moderate and excessive hypertrophy, provided systolic wall stress and hence the myocardial oxygen consumption are not increased. It is concluded that the appropriateness of left ventricular hypertrophy, as a result of mass-to-volume ratio and stress, is a major determinant of left ventricular performance, of coronary blood flow, and of myocardial oxygen consumption.
Importance of chloride for deoxycorticosterone acetate-salt hypertension in the rat.
Authors: Passmore J C , Whitescarver S A , Ott C E , Kotchen T A
Published: August 2012

Selective dietary sodium loading (without chloride) fails to produce hypertension in the Dahl salt-sensitive rat. This study attempted to evaluate the effect of selective sodium loading on blood pressure in another NaCl-dependent model of hypertension--deoxycorticosterone acetate (DOCA)-salt hypertension. Three groups of uninephrectomized rats were studied for 32 days on one of the following regimens: (1) high NaCl diet plus DOCA, (2) high dietary sodium intake without chloride plus DOCA, and (3) high NaCl diet without DOCA. Both indirect and direct arterial pressure were higher (p less than 0.01) in the DOCA-NaCl group than in the other two groups. In the two DOCA-treated groups, net sodium and potassium balance and total carcass sodium and potassium content did not differ. In the DOCA-NaCl group, higher blood pressures were associated with a more positive chloride balance and total carcass chloride content (p less than 0.01), an expanded extracellular fluid volume (p less than 0.05), and increased renal vascular resistance (p less than 0.01). Higher renal vascular resistance in DOCA-NaCl animals suggests that chloride contributes to NaCl-induced vasoconstriction.