bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of risk status on treatment criteria. Implications of hypertension trials.
Authors: Browner W S , Hulley S B
Published: August 2012

When deciding whether to treat a patient with hypertension, clinicians must balance the benefit of treatment against its adverse effects. In the absence of an interaction, the multiplicative model of risk implies that the absolute benefit of treatment is related to the underlying risk of an adverse outcome. Thus, each additional risk factor multiplies the absolute benefit of treating hypertension. Analyses of data from subgroups in clinical trials of hypertension treatment suggest that this model is usually valid. In contrast, the adverse effects of treatment are usually unrelated to other risk factors. Thus, the cutoff point for treatment differs in different individuals: setting a single treatment threshold and goal for the entire population is not appropriate. Patients who are at high absolute risk because of prior coronary artery disease or other risk factors have a greater potential absolute benefit, and such patients deserve a low threshold and goal, such as a diastolic blood pressure of 90 mm Hg. Conversely, persons at low risk, such as white women without other risk factors, do not require such aggressive management.
Increased treatment of hypertension does not explain the decline in stroke mortality in the United States, 1970-1980.
Authors: Bonita R , Beaglehole R
Published: August 2012

The steady decline in mortality from stroke in the United States accelerated markedly in the 1970s. It has been widely assumed that an increase in the rate of treatment of hypertension is the most likely explanation for this major public health achievement. An analysis of available information, however, suggests that improvements in the community control of hypertension in the United States in the period 1970-1980 have contributed in only a minor way. There were 45,357 fewer deaths from stroke in 1980 among those aged 35-74 years than might have been expected if the death rates had stayed the same as in 1970. Data from the National Health and Nutrition Surveys indicate that six million more people received antihypertensive medication in 1980 than in 1970. Results from a pooled analysis of randomized controlled trials of the treatment of hypertension suggest that between 6% and 16% of the reduction in stroke mortality was due to the increased treatment of hypertension. Epidemiological observations indicate that between 16% and 25% of the overall decline in stroke mortality can be attributed to the treatment of hypertension, suggesting that clinical trials probably underestimate the community-wide benefits of treatment. These results also suggest that at least three quarters of the decline in stroke mortality in the United States in the period 1970-1980 is due to factors other than antihypertensive treatment.
Cardiovascular actions of vasopressin at the ventrolateral medulla.
Authors: Andreatta-Van Leyen S , Averill D B , Ferrario C M
Published: August 2012

Vasopressin acts at a number of sites in the central nervous system to alter arterial pressure. This study investigated the hypothesis that vasopressin acts at the rostral ventrolateral medulla to increase arterial pressure. The rostral pressor area of the medulla oblongata was exposed in urethane-anesthetized rats prepared for topical application of vasopressin. A 3-minute application of vasopressin (range 10(-8) to 10(-3) M) produced dose-dependent increases in arterial pressure that averaged between 2 +/- 1 and 65 +/- 11 mm Hg (p less than 0.01). Tachycardia was not a consistent response at any concentration of vasopressin. Intravenous administration of a V1 vasopressin antagonist did not modify the pressor response produced by topical application of vasopressin (10(-4) M). Application of the V1 antagonist to the rostral pressor area, however, prevented the production of a pressor effect to subsequent topical application of vasopressin (10(-4) M). These experiments suggest that vasopressin stimulates the activity of vasomotor neurons in the rostral ventrolateral medulla by a mechanism that involves a neuronal V1 receptor.
Distribution of prostaglandins E2 and 6-keto-F1 alpha production in dog kidneys.
Authors: Refoyo A , Bolterman R J , Bentley M D , Fiksen-Olsen M J , Sandberg S M , Romero J C
Published: August 2012

Little is known about the distribution of prostaglandin E2 (PGE2) and prostacyclin (PGI2) production in the canine kidney. To determine the basal and stimulated profiles of PGE2 and PGI2 production along the corticomedullary axis of the dog kidney, a slice (0.5 mm thick, 10-50 mg) was obtained from six equally spaced zones along the axis (zone 1, medullary crest; zones 2 and 3, inner medulla; zone 4, outer medulla; and zones 5 and 6, cortex) and was divided into equal halves. One half of the slice was incubated with Krebs-Ringer buffer containing arachidonic acid (6.6 x 10(-4) M), bradykinin (9.4 x 10(-6) M), or indomethacin (10(-5) M), whereas the remaining half of each slice was similarly incubated in Krebs-Ringer buffer alone. The production of PGE2 and 6-keto-PGF1 alpha (the stable metabolite of PGI2) was determined by radioimmunoassay. Under basal conditions, both PGE2 and 6-keto-PGF1 alpha were highest in the innermost zones of the inner medulla (PGE2, 3,328 +/- 549 pg/mg; 6-keto-PGF 1 alpha, 1,611 +/- 129 pg/mg) and decreased exponentially to low levels in the cortex (PGE2, undetectable; 6-keto-PGF1 alpha, 13 +/- 2 pg/mg); this production was inhibited by indomethacin. Arachidonic acid significantly increased the production of PGE2 in all zones of the kidney and the production of 6-keto-PGF1 alpha only in zones 3-6.(ABSTRACT TRUNCATED AT 250 WORDS)
Deoxycorticosterone hypertension in the intact weanling rat without salt loading.
Authors: Rodriguez-Sargent C , Torres-Negron I , Cangiano J L , Martinez-Maldonado M
Published: August 2012

Deoxycorticosterone (DOC) hypertension in the rat is generally induced in rats at an age of approximately 3 months. Both uninephrectomy and a high sodium diet are necessary, however, to induce DOC hypertension. Considering the inability of the developing kidney to adequately excrete a sodium load, we studied the possibility that DOC alone might induce hypertension when treatment is initiated in rats at the age of 21 days. The contribution of volume expansion as a factor mediating the pressor response to DOC was assessed in rats given a high sodium diet instead of DOC. Systolic blood pressure increased in DOC-treated rats within 3 weeks. Although systolic blood pressure also increased in rats on a high sodium diet, the increase was transient and of a lesser magnitude than that observed in DOC-treated rats. The rise in blood pressure in both groups of rats was associated with suppression of plasma renin activity and aldosterone concentration. Furthermore, extracellular fluid volume was similarly increased in DOC-treated rats and rats given a high sodium diet. Consistent with these data, DOC-treated rats showed an exaggerated natriuretic response to acute saline loading as compared with a vehicle-treated control group. Discontinuation of DOC treatment after 5 weeks led to normalization of all variables studied including blood pressure. Yet, when DOC was continued for 8 weeks, stopping treatment did not lower blood pressure despite normalization of the renin-angiotensin-aldosterone system and the natriuretic response to saline loading. In contrast, discontinuation of the high sodium diet after 8 weeks normalized blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Pressor response to norepinephrine in essential hypertension. A study in families.
Authors: De Lima J J , Dias M M , Bernardes-Silva H , Bellotti G
Published: August 2012

Study of pressor response to graded, increased doses of infused norepinephrine in patients with essential hypertension, their normotensive siblings, and normotensive control subjects unrelated to the patients and without a family history of hypertension indicated an increased response in the two former groups. Comparison of the dose-response curves in the three groups showed that the difference in response was due to a reduced threshold to norepinephrine in patients and their siblings and not to differences in the slopes of the dose-response curves. These alterations were not paralleled by differences in heart rate responses.
Reversal of hyperreactivity to bradykinin in renal hypertensive rats.
Authors: Camacho A A , Salgado M C , Krieger E M
Published: August 2012

Increased blood pressure responsiveness to bradykinin in comparison with other vasodilator agents was demonstrated in rats with long-term one-kidney and two-kidney, one clip hypertension. In the present study, we analyzed the reactivity to intra-aortically injected bradykinin in unanesthetized one-kidney, one clip hypertensive rats during the control period and 1, 5, and 8 hours after reversal of hypertension after removal of the renal artery constriction. One and 5 hours after unclipping the renal artery, the mean blood pressure decreased markedly (from 195 +/- 7 to 124 +/- 8 and 145 +/- 9 mm Hg, respectively), whereas the hyperreactivity to bradykinin reverted only slightly, and the responses to nitroprusside remained unchanged. In another group of hypertensive rats examined 8 hours after unclipping (pressure decreased from 192 +/- 4 to 143 +/- 8 mm Hg), the hyperreactivity to bradykinin had partially reverted. Significantly larger doses of bradykinin were necessary to produce the same decrease in blood pressure when compared with the control period (16.4 +/- 2.0 vs. 7.2 +/- 1.2 ng). The same degree of reversal of hyperreactivity to bradykinin was observed when the blood pressure of hypertensive rats was reduced (from 207 +/- 8 to 143 +/- 5 mm Hg) during 1 hour by hydralazine injection. Complete reversibility of bradykinin hyperreactivity was produced by nitroprusside infusion (from 201 +/- 13 to 142 +/- 10 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)
Lenticular rubidium uptake and plasma renin activity in weanling cataract-prone salt-sensitive rats.
Authors: Rodríguez-Sargent C , Estapé E S , Rodríguez-Santiago A , Ramos V L , Irizarry J E , Cangiano J L , Martínez-Maldonado M
Published: August 2012

Our earlier studies of cataracts in Dahl salt-sensitive (DS) rats suggested the possibility of altered lens ion transport as a contributing factor in cataractogenesis in this genetic model. We also observed that those weanling DS rats with the greatest pressor response to a high salt diet eventually developed cataracts, and that changes in salt intake modified cataract formation. In the present studies, we measured lens 86Rb uptake as an index of sodium-potassium adenosine triphosphatase [(Na+,K+)-ATPase] activity in weanling DS rats before the development of cataracts or sustained hypertension. Additionally, plasma renin activity was measured to indirectly assess our hypothesis that the difference between cataract-prone DS rats and DS rats unlikely to develop cataracts might be a difference in degree of salt sensitivity. At the age of 4 weeks, 50 DS and 25 salt-resistant (DR) rats were given a high sodium diet for 2 weeks, at which time the rats were divided into three groups based on the systolic blood pressure response, that is, cataract-prone DS rats with systolic blood pressure equal to or greater than 155 mm Hg, DS rats unlikely to develop cataracts with systolic blood pressure less than or equal to 125 mm Hg, and DR rats. Lens and aqueous humor Na+ and K+, lens dry weight, and water content were not significantly different among the three groups of weanling rats. Plasma renin activity was lowest in cataract-prone DS rats and low in DS rats unlikely to develop cataracts when compared with values in DR rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Biological activity of angiotensin-(1-7) heptapeptide in the hamster heart.
Authors: Kumagai H , Khosla M , Ferrario C , Fouad-Tarazi F M
Published: August 2012

Angiotensin II has been reported to have both a positive inotropic effect and a coronary constrictor action in the hamster heart. To study the contribution to these responses of phenylalanine in position 8, we assessed the direct cardiac effects of angiotensin-(1-7), which lacks phenylalanine in position 8. Syrian hamsters were used to determine the effects of angiotensin-(1-7) on cardiac performance in the diseased and normal hearts. We used the isolated isovolumic heart preparation perfused either at a constant pressure of 50 mm Hg or at a constant coronary (myocardial) flow rate of 7 ml/min (seven cardiomyopathic hamsters [CMH] and seven normal hamsters [NH] in each subgroup). At constant perfusion pressure, coronary (myocardial) flow rate decreased (p less than 0.01) in both CMH and NH (-31 +/- 8% vs. -39 +/- 4% of baseline, respectively); but the percent decrease in left ventricular pressure and the first derivative of left ventricular pressure over time (LV + dP/dt) was significant only in NH (-8 +/- 1% and -9 +/- 4%) but not in CMH (-14 +/- 5% and -21 +/- 8%). On the other hand, at a constant coronary (myocardial) flow rate, left ventricular pressure and LV + dP/dt tended to increase in both CMH and NH (+10 +/- 3% and +6 +/- 2% of baseline vs. +7 +/- 7% and +7 +/- 5%, respectively) but these changes were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Actions of angiotensin peptides after partial denervation of the solitary tract nucleus.
Authors: Campagnole-Santos M J , Diz D I , Ferrario C M
Published: August 2012

We determined the excitatory effects of direct nucleus tractus solitarii injection of angiotensin peptides after the sinoaortic nerves were cut unilaterally in rats under halothane anesthesia. Twenty-four hours later, recordings of mean arterial pressure and heart rate were obtained during injections of 2.5 ng angiotensin II or angiotensin-(1-7) in chloralose-urethane-anesthetized rats. Both peptides caused reductions in pressure and heart rate after nucleus tractus solitarii injections. In unilateral sinoaortic denervated rats, the hypotension and bradycardia produced with angiotensin II injections in either the ipsilateral (denervated) or contralateral (nondenervated) nucleus tractus solitarii were comparable. Angiotensin-(1-7), however, produced a larger decrease in pressure on the denervated side when compared with the nondenervated side. There were no differences in baseline pressure or heart rate between control rats and those with unilateral sinoaortic denervations. The effects of both angiotensin II and angiotensin-(1-7) were blocked by previous administration of the angiotensin II antagonist [Sar1,Thr8]angiotensin II into the nucleus tractus solitarii. Assessment of angiotensin II binding sites in the solitary-vagal complex 24 hours after denervation showed a 13% reduction in angiotensin receptors. These findings confirm that both angiotensin II and angiotensin-(1-7) express biological activity through receptor-mediated actions in the dorsal medulla oblongata. That the effects produced by angiotensin II do not require the integrity of baroreceptor input further suggests that the receptors responsible for the acute cardiovascular actions of this peptide reside on postsynaptic elements in the vagal-solitary complex.
Comparison of the effect of endothelin on microvessels and macrovessels in Goldblatt II and deoxycorticosterone acetate-salt hypertensive rats.
Authors: de Carvalho M H , Nigro D , Scivoletto R , Barbeiro H V , de Oliveira M A , de Nucci G , Fortes Z B
Published: August 2012

The response to endothelin, a novel 21-amino acid peptide, is investigated in isolated aortas with and without endothelium and in mesenteric microvessels in vivo-in situ, in Goldblatt II (GII) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Median effective concentrations and maximal responses to endothelin did not differ in aortas with endothelium isolated from GII, DOCA-salt hypertensive, and control rats. After removal of the endothelium, the potentiation of the aorta responses to endothelin was of the same magnitude in hypertensive and control rats. A closed-circuit television system was used to observe the microvascular bed of the exteriorized mesentery of anesthetized GII, DOCA-salt hypertensive, and control rats. The time necessary to induce a vasoconstrictor response was determined after the topical application of endothelin. Vessel diameters at rest and after endothelin application were also estimated. At the microcirculatory level, a greater reactivity to endothelin was observed in both hypertensive rat groups, whereas higher sensitivity to endothelin was recorded in the GII hypertensive microvessel preparations alone. It is suggested that the increased response to endothelin observed in hypertensive rats might be due to abnormal sensitivity or reactivity of the microvessels of these rats reflecting an alteration of the contractile sequence possibly at the plasma membrane level, or due to both. Endothelial dysfunction at the microcirculatory level, however, cannot be dismissed.
Inhibition of human mesangial cell proliferation by calcium channel blockers.
Authors: Shultz P J , Raij L
Published: August 2012

Human mesangial cells in culture proliferate in response to platelet-derived growth factor (PDGF) and thrombin. Both of these agents also induce changes in cytosolic calcium that are dependent on both mobilization of intracellular calcium and influx of extracellular calcium. We hypothesized that calcium channel blockers, by preventing influx of extracellular calcium, may inhibit proliferation induced by these mitogens. We found that three different calcium channel blockers, diltiazem, nifedipine, and verapamil, were able to significantly inhibit [3H]thymidine incorporation into human mesangial cells induced by either PDGF or thrombin. The inhibitory effect of these agents was significant at 10(-5) M. The calcium channel blockers also attenuated the increases in cell number and percentage of labeled nuclei induced by these mitogens. In contrast, dantrolene, an inhibitor of intracellular calcium mobilization, had no significant effect on [3H]thymidine incorporation by PDGF or thrombin. Finally, the calcium channel agonist, Bay K 8644 was found to stimulate [3H]thymidine incorporation into mesangial cells. Although the mechanisms for these effects of calcium channel blockers are not proven, these studies suggest that influx of extracellular calcium is an important signal in mitogen-induced mesangial proliferation and that these agents can be beneficial in preventing or attenuating renal diseases characterized by proliferation of these cells.
Dietary linoleic acid prevents the development of deoxycorticosterone acetate-salt hypertension.
Authors: Kawahara J , Sano H , Kubota Y , Hattori K , Miki T , Suzuki H , Fukuzaki H
Published: August 2012

The aim of this study was to elucidate the effect of dietary variations of linoleic acid on the development of deoxycorticosterone acetate (DOCA)-salt hypertension in rats. All rats were divided into three groups and fed one of the following isocaloric diets with 8% NaCl: a high linoleic acid (HLA) (20% sunflower oil), a moderate linoleic acid (5% lard oil + 15% sunflower oil), or a low linoleic acid (DLA) (20% lard oil). After 4 weeks of feeding, we determined intraerythrocyte sodium, potassium, and magnesium concentrations, intra-aortic and lymphocyte magnesium content, and erythrocyte ouabain-sensitive 22Na efflux rate constant. Cytoplasmic free calcium concentration of lymphocytes from thymus was also determined with quin-2 as a fluorescent indicator. In the HLA group, the elevation of systolic blood pressure was significantly attenuated, and intraerythrocyte sodium concentration was significantly lower than in the DLA group. There were greater intraerythrocyte potassium and magnesium concentrations, intra-aortic and lymphocyte magnesium contents, and erythrocyte ouabain-sensitive 22Na efflux rate constant in the HLA group as compared with other groups. Cytoplasmic free calcium concentration in the HLA group was significantly lower than in other groups. Systolic blood pressure significantly correlated negatively with intraerythrocyte and intra-aortic magnesium concentrations and intraerythrocyte potassium concentration, and correlated positively with cytoplasmic free calcium concentration. Erythrocyte ouabain-sensitive 22Na efflux rate constant significantly correlated positively with intraerythrocyte magnesium concentration. These findings suggest that dietary linoleic acid can attenuate the development of DOCA-salt hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Pressor hormones in elderly hypertensive persons. Racial differences.
Authors: Bursztyn M , Bresnahan M , Gavras I , Gavras H
Published: August 2012

The purpose of this study was to examine pressor hormones and platelet alpha 2-adrenergic receptors in elderly unmedicated free-living subjects. Eighty-seven subjects, 70 +/- 5 years old (mean +/- SD), hypertensive or normotensive (blood pressure less than 160/90 mm Hg) were recruited for measurement of blood levels of norepinephrine, epinephrine, and vasopressin, as well as density and affinity of alpha 2-adrenergic receptors from platelet membranes, assessed by maximal binding (Bmax) and dissociation constant (Kd) of rauwolscine. They were separated into white hypertensive (n = 22) or normotensive (n = 41), and black hypertensive (n = 11) or normotensive (n = 13) groups, with similar age distribution throughout and similar blood pressure levels in the hypertensive and normotensive groups. Vasopressin was higher in the black hypertensive than white hypertensive group (1.5 +/- 1.0 vs. 0.7 +/- 0.5 pg/ml, respectively, p less than 0.005), whereas epinephrine correlated inversely with diastolic blood pressure (r = -0.7, p less than 0.02, in the black hypertensive group). Kd was higher in the black normotensive group than in the other groups (1.6 +/- 0.6 vs. 1.0 +/- 0.2, 1.1 +/- 0.3, or 1.0 +/- 0.3 nM in the white normotensive, black hypertensive, or white hypertensive group, respectively, p less than 0.002). Bmax was no different among groups but was significantly correlated with vasopressin levels for the whole group (r = 0.4, p less than 0.0004) although no such correlation existed within the black hypertensive group. The data suggest that various vasoconstrictor systems participate to different extents in the mechanisms generating and sustaining hypertension in elderly white and black subjects.
Clinical interaction of salt and weight change on blood pressure level.
Authors: Prineas R J
Published: August 2012

Studies that examine the effect of altered body weight or dietary sodium on blood pressure level are reviewed. Emphasis is placed on studies that compare the effects of weight reduction or sodium restriction in separate comparison groups or analyze the independent effect of the two intervention modalities in multiple regression analysis. Additional analyses of the Hypertension Prevention Trial data are presented. Most studies, where comparison can be made, suggest a greater effect for weight reduction than for the achieved, moderate, or short-term reduction in sodium intake on subsequent lowering of blood pressure; the lowering effect on blood pressure of weight reduction is independent of the effect of dietary sodium restriction. However, long-term (over a year) substantial reductions (up to 70 meq/day) of dietary sodium have not been achieved in comparative trials, nor are the effects of combined weight and sodium reduction in the prevention and treatment of hypertension quantified. Future studies and potential problems are discussed.
Sodium-potassium interaction in hypertension and hypertensive cardiovascular disease.
Authors: Langford H G
Published: August 2012

Epidemiological evidence suggests that low potassium intake is associated with the probability of occurrence of hypertension and stroke. The short-term response to increased potassium intake is increased sodium excretion as well as increased potassium excretion; the short-term response to increased sodium intake is increased potassium excretion as well as increased sodium excretion. In some experimental studies, increased amounts of potassium have been able to block the noxious influences of sodium. Sodium and potassium must be concomitantly considered in the investigation of the association of either of these cations with hypertension and cardiovascular disease. The chloride ion is also important for sodium's effects; its importance in potassium's effects has not been extensively explored.
A perspective on the salt-blood pressure relation.
Authors: Dustan H P
Published: August 2012

Current recommendations for a population-wide decrease in dietary salt consumption come from a conclusion that a substantial portion of the population with essential hypertension is salt-sensitive. It is difficult to determine the appropriateness of these recommendations because of critical gaps in knowledge of the salt-blood pressure relation. There is no agreement on a definition of salt-sensitive blood pressure changes. There is no consensus about mechanisms of changes; several have been suggested but none seems universal. In fact, differing results suggest marked heterogeneity in the mechanisms of salt-sensitive hypertension, and some evidence points to the possibility that arterial pressure of hypertensive subjects is controlled differently than that of normotensive subjects during manipulation of salt intake. Because salt-sensitive blood pressure changes are not always related to the magnitude of the positive sodium balance, it seems possible that for some people the current recommendations for modest dietary sodium restriction may be inadequate to influence blood pressure control for the prevention of hypertension.
Health promotion roles of the federal government and food industry in nutrition and blood pressure.
Authors: Ernst N D
Published: August 2012

Some principal activities of government that pertain to nutrition and blood pressure are education, information, dietary guidance, food regulatory practices, health and nutrition monitoring, biomedical research and training, and legislation. The food industry, in turn, influences the marketplace and food consumption by its response to government activities and policies. Dietary guidance recommendations call for moderation of dietary intake, improved nutrition, and greater availability in food choices in the marketplace that are consistent with dietary recommendations to reduce chronic disease risk. Health and nutrition monitoring allows measurement of the effectiveness of moderating dietary intake and controlling hypertension. Adequate support of education, nutrition and health monitoring, and biomedical research and training is necessary to control and prevent hypertension. Cooperation between government and industry can contribute to the decline in cardiovascular disease, which in 1987 cost this nation in excess of $135 billion.
A perspective on reducing salt intake.
Authors: Hegsted D M
Published: August 2012

Epidemiological, clinical, and experimental evidence links excessive salt consumption to hypertension; there appears to be no evidence that it is beneficial. I conclude that it should be public policy to advise and help Americans to reduce their salt intake. Because even mild hypertension increases risk, the overall problem does not appear to be amenable to treatment, although treatment for those with clinical hypertension will always be needed. There appears to be little likelihood that identification of those "at risk" will be successful, nor does it appear that we have the capacity at this time to conduct successful preventive field trials. It is difficult for the individual to modify his diet alone. The successful strategy is to modify the food supply by changing public demand. The public responds to dietary advice if acceptable and identifiable products are available. Because most of the salt is in commercially prepared foods and because their consumption will increase in the future, the major responsibility for lowering salt consumption will fall on the food manufacturers. They are beginning to respond, and there appears to be ample opportunity for them to reduce the salt content of foods markedly. Our temporary objectives, however, should be modest, because unrealistic objectives only discourage those who attempt to follow them.
Genetic traits related to hypertension and electrolyte metabolism.
Authors: Williams R R , Hasstedt S J , Hunt S C , Wu L L , Hopkins P N , Berry T D , Stults B M , Barlow G K , Kuida H
Published: August 2012

The genetic and cultural heritability and intercorrelation of traits related to hypertension have been carried out in 98 Utah pedigrees (2,500 person) and 58 sibships with two or more hypertensive persons (131 hypertensive persons). Although none of these traits has been established as a marker for "sodium-sensitive hypertension," many of them are related at least indirectly to both electrolyte metabolism and risk of hypertension. Significant recessive monogenic effects and high total heritability (52-84%) were found for urinary kallikrein, high fat pattern index, intraerythrocytic sodium, Na-Li countertransport, and ouabain binding sites. Familial correlations more strongly attributable to shared environment than to genetic effects were found for Na,K-ATPase pump activity, intraerythrocytic magnesium, plasma digoxin-like factor, plasma renin activity, and plasma sodium concentration. All anthropometric variables tested showed highly significant genetic heritability with low and insignificant shared family environmental effects. Several of the genetically determined cellular cation tests also correlated with other genetic traits including plasma lipids, anthropometric measurements, and other cellular cation tests. Among hypertensive individuals with familial dyslipidemic hypertension, plasma insulin levels correlated with obesity and lipid abnormalities and with several cellular cation flux tests associated with hypertension.
Abnormal cardiovascular reactivity in borderline and mild essential hypertension.
Authors: de Champlain J , Petrovich M , Gonzalez M , Lebeau R , Nadeau R
Published: August 2012

Cardiovascular and hemodynamic reactivity was evaluated with M-mode echocardiography, phonocardiography, and carotidography in correlation with circulating catecholamine levels in 25 normotensive subjects, 15 borderline hypertensive patients, and 42 mildly hypertensive patients during isometric exercise at 30% of the maximum force for 3 minutes. At rest, norepinephrine and epinephrine levels were significantly higher, and the cardiac index was similarly increased in both groups of hypertensive patients, but the cardiac mass index was significantly increased only in the mildly hypertensive group. During isometric exercise, the sympathoadrenal reactivity as well as the pressor and chronotropic responses were similar in normotensive subjects and both groups of hypertensive patients. However, the variations in blood pressure were achieved through totally different hemodynamic mechanisms in normotensive subjects and hypertensive patients. In normotensive subjects, the increase in blood pressure could be linked mainly to an increase in cardiac contractility and performance, whereas in either group of hypertensive patients, the increase in blood pressure was mainly associated with an increase in peripheral resistance. These observations are consistent with the hypothesis of a blunted beta-adrenergic reactivity and a predominance of alpha-adrenergic vascular reactivity in borderline and mildly hypertensive patients. This phenomenon, which appears to be unrelated to age or severity of hypertension, could be an important mechanism underlying the development of hypertension in humans.
Methodological problems in evaluation of cardiovascular effects of stress in humans.
Authors: Parati G , Trazzi S , Ravogli A , Casadei R , Omboni S , Mancia G
Published: August 2012

Cardiovascular effects of stress in humans are often assessed by application of physical or emotional stimuli in a laboratory environment. Although this method provides important information, these procedures have several limitations. First, blood pressure and heart rate responses to laboratory stressors are characterized by a limited within-subject reproducibility. Second, there is poor correlation between blood pressure and heart rate responses to different stressors, which implies that individual reaction to stress may be estimated differently according to the test used. Finally, these responses bear only a limited relation to 24-hour or daytime blood pressure variability, that is, they reflect to only a limited extent the tendency of blood pressure to vary during daily activities. If assessed by techniques that allow blood pressure to be continuously recorded for 24 hours in ambulatory subjects, blood pressure variability represents a possible approach to observation of cardiovascular reactivity away from an artificial laboratory environment. However, whether blood pressure variability should be expressed as a percentage or in absolute values is controversial. Furthermore, although naturally occurring stress may markedly increase blood pressure, 24-hour blood pressure variations also depend on factors that are not related to emotional stimuli. Thus, the study of cardiovascular responses to stress in humans encounters several problems, regardless of the method used.
Management of hypertension by reduction in sympathetic activity.
Authors: Mathias C J
Published: August 2012

The sympathetic nervous system may initiate or maintain hypertension, and a range of approaches that reduce sympathetic activity is often of value in management. These may include nonpharmacological methods, such as the various forms of behavioral therapy (e.g., meditation, relaxation, and biofeedback techniques); weight reduction and avoidance of particular foods and agents that stimulate sympathetic activity (including caffeine and alcohol), and regular physical exercise. Pharmacological therapy includes centrally acting drugs such as alpha-methyldopa, clonidine, and reserpine; ganglionic blockers such as hexamethonium; agents acting on sympathetic nerve terminals such as guanethidine and debrisoquine; and drugs that may act at multiple sites, such as the beta-adrenergic blockers. The role of reducing sympathetic activity in the current management of hypertension and its complications is considered in this overview.
Systolic blood pressure levels in black populations in sub-Sahara Africa, the West Indies, and the United States: a meta-analysis.
Authors: Wilson T W , Hollifield L R , Grim C E
Published: August 2012

Average systolic blood pressure levels from epidemiological studies conducted on black populations in sub-Sahara Africa were pooled and compared with pooled systolic blood pressure levels from black populations in the northern portion of the Western hemisphere (the West Indies and the United States). Studies published in English that listed systolic blood pressure means and standard deviations and sample sizes in 40-49-year-old men and women were included. Overall, systolic blood pressure levels were higher (p less than 0.05) in blacks from the northern Western hemisphere than in blacks from sub-Sahara Africa for both men (12 mm Hg higher) and women (13 mm Hg higher). The analysis was also conducted on regions within sub-Sahara Africa and in rural and urban subgroups. Systolic blood pressure was lower (p less than 0.05) in East Africa than in the other three regions within Africa for both sexes. Overall, urban blacks within Africa had higher systolic blood pressures (p less than 0.05) than rural blacks for both sexes. In the northern Western hemisphere, rural blacks had higher systolic blood pressures (p less than 0.05) than urban blacks for both sexes. Studies should be designed with standardized methods to unravel these intraracial differences in blood pressure levels.
Blood pressure and high blood pressure. Aspects of risk.
Authors: Stamler J
Published: August 2012

This report deals with three aspects of risk related to blood pressure and high blood pressure. The first aspect of risk concerns distributions of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the adult population and their relation to long-term risk of morbidity and mortality. By middle age, only a minority (about 20%) of Americans have optimal SBP and DBP levels, less than 120 mm Hg and less than 80 mm Hg, respectively. For the majority with higher levels, risks of major clinical events, including death from cardiovascular diseases and from all causes, are markedly increased. The relations of SBP and DBP with risk are strong, continuous, and graded. Risk is sizable not only for persons with high blood pressure by usual clinical criteria (SBP greater than or equal to 140 mm Hg or DBP greater than or equal to 90 mm Hg), but also for those with "high-normal" blood pressure (e.g., SBP 130-139 mm Hg or DBP 80-89 mm Hg). Thus, the blood pressure problem is a population-wide one and requires for its control a combined population-wide and high-risk strategy. A major component of this strategy must be nutritional-hygienic measures for the primary prevention of the rise in blood pressure during adulthood and of high blood pressure (i.e., primary prevention not only of the complications of high blood pressure but also of high blood pressure itself) through improved lifestyles having the potential to shift downward the blood pressure distribution of the whole population. The second aspect of risk concerns the known risk factors (i.e., aspects of modern lifestyle) leading to the mass occurrence of blood pressure rise during adulthood and of high blood pressure. These risk factors are high salt intake, high dietary sodium/potassium ratio, calorie imbalance and resultant obesity, and high alcohol intake. The extensive data base establishing the role of these common traits in the etiology of the blood pressure/high blood pressure problem is the scientific foundation for efforts to achieve the primary prevention of high blood pressure. The third aspect of risk relates to the combined impact of other risk factors along with blood pressure-high blood pressure in markedly increasing the probabilities of morbidity and mortality (e.g., "rich" diet, diet-dependent serum cholesterol and uric acid, smoking, diabetes, and target-organ damage). Prevention and control of lifestyle-related traits are essential components of the strategy for dealing with the blood pressure-high blood pressure problem.
Effect of converting enzyme inhibition on allograft-induced arterial wall injury and response.
Authors: Plissonnier D , Amichot G , Duriez M , Legagneux J , Levy B I , Michel J B
Published: August 2012

Converting enzyme inhibition (CEI) can prevent myointimal proliferation after arterial wall balloon injury. Because intimal proliferation is the main long-term complication of chronic vascular rejection, we tested the effect of CEI (perindopril, 1 mg/kg twice a day) on arterial rejection-induced intimal proliferation, using a model of aortic allograft in normotensive Wistar-Kyoto and spontaneously hypertensive rats. Eight-week-old rats were grafted and studied 2 months later. The structural parameters of the transplanted aortic wall were measured by morphometric analysis of specifically stained, formol-fixed sections. CEI did not prevent adventitial inflammatory infiltration but significantly increased the number of living cells and prevented the partial destruction of elastic laminae in the media, thereby increasing medial thickness to close to that of sham-operated controls. CEI significantly decreased intimal thickness and intimal collagen density, without changing the absolute number of intimal smooth muscle cells. The intimal thickness and the intimal collagen density were significantly correlated with the effect of CEI on blood pressure. CEI partially prevented the consequences of immune injury to the media within the arterial wall, probably by suppressing the proinflammatory activity of angiotensin II. It also decreased the recipient arterial wall response by acting more on the trophicity of intimal cells and on their ability to produce collagen rather than by directly inhibiting smooth muscle cell proliferation in our model of arterial allograft.
Inhibition of converting enzyme and neointima formation after vascular injury in rabbits and guinea pigs.
Authors: Clozel J P , Hess P , Michael C , Schietinger K , Baumgartner H R
Published: August 2012

Recently, it has been shown that cilazapril could suppress neointima formation after vascular injury in rats. The goal of the present study was to confirm these findings in guinea pigs and rabbits. Vascular injury was produced by ballooning the right carotid artery of guinea pigs and the right iliac artery of rabbits. The animals were treated with either placebo or cilazapril (30 mg/kg/day and 3 mg/kg/day in guinea pigs and rabbits, respectively). Cilazapril decreased by 42% (p less than 0.001) the neointima area in the guinea pig but was ineffective in rabbits. However, in rabbits, doses of cilazapril higher than 3 mg/kg could not be given because of known toxicological effects in the rabbit. We conclude that the protective effect of cilazapril described in rats also is observed in guinea pigs. However, in rabbits, the maximal tolerated dose of cilazapril was ineffective. These results underline the importance of ongoing clinical studies to evaluate if, in humans, cilazapril inhibits restenosis after coronary angioplasty.
Heparin and cilazapril together inhibit injury-induced intimal hyperplasia.
Authors: Clowes A W , Clowes M M , Vergel S C , Müller R K , Powell J S , Hefti F , Baumgartner H R
Published: August 2012

Both heparin and the angiotensin converting enzyme inhibitor cilazapril inhibit intimal thickening in rat carotid arteries injured by the passage of a balloon catheter. The purpose of this study was to determine if combinations of the two drugs were more effective than either drug alone and whether the effect could be accounted for by inhibition of smooth muscle cell proliferation. Heparin (0.1-0.3 mg/kg/hr) administered by continuous intravenous infusion with or without cilazapril (0-25 mg/kg/day p.o.) produced a dose-dependent inhibition of smooth muscle accumulation at 14 days after rat carotid ballooning. At the lower doses, the inhibitory effects of heparin and cilazapril were additive when the drugs were used together. This overall effect on growth was reflected in decreased smooth muscle cell proliferation at 2 and 7 days. A 7-day course of heparin combined with cilazapril, a regimen that might be applicable in the clinical setting, produced an 80% inhibition of intimal thickening at 28 days. These results provide evidence that heparin and cilazapril together might prove to be more effective than either drug alone in the control of intimal hyperplasia after arterial injury.
Endothelium and growth factors in vascular remodeling of hypertension.
Authors: Dzau V J , Gibbons G H
Published: August 2012

The pioneering work of Furchgott, Moncada, and Vane has clearly established that the endothelium plays a critical role in the regulation of vascular tone. The endothelium produces several potent vasoactive substances, including vasodilators such as endothelium-derived relaxing factor and prostacyclin as well as vasoconstrictors such as angiotensin II and endothelin. These vasoactive substances not only have short-term effects on vascular tone but also appear to induce long-term effects on vascular structure. This process of vascular remodeling involves cell growth or regression and extracellular matrix expansion or contraction. As the interface between the bloodstream and the vessel wall, the endothelium plays a pivotal role in sensing and transducing the stimulus that induces vascular remodeling as well as producing the mediators that alter cell growth and the composition of the extracellular matrix. The endothelium maintains homeostasis within the vasculature by a balance between vasodilators and vasoconstrictors or growth inhibitors and growth promoters. Endothelial cell dysfunction may alter the delicate balance of mediators necessary to maintain homeostasis. Indeed, endothelial cell dysfunction is a common pathogenetic defect in animal models of hypertension as well as in hypertensive humans. Further understanding of the cellular and molecular mechanisms of vascular remodeling induced by endothelial cell-derived mediators may have important implications in the pathogenesis and treatment of hypertension.
Medullipin system. Generation of medullipin II by isolated kidney-liver perfusion.
Authors: Muirhead E E , Brooks B , Byers L W , Brown P , Pitcock J A
Published: August 2012

Perfusion of isolated normal rat kidneys with blood at elevated blood pressure (180-200 mm Hg) followed by perfusion of the renal perfusate through an isolated normal rat liver under venous pressure yielded in the plasma of the hepatic effluent a vasodepressor lipid having the chromatographic and biological characteristics of medullipin II. These findings support the view that medullipin II is the final product of the renohepatic axis of blood pressure control.
Unifying hypothesis of sodium and water regulation in health and disease.
Authors: Schrier R W , Howard R L
Published: August 2012

Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome, and pregnancy. Nonosmotic vasopressin release has been implicated in the water retention of these edematous disorders. The nonosmotic release of vasopressin is consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems in both experimental animals and in edematous patients. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin and activation of the renin-angiotensin system. These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. Neither total extracellular fluid volume nor blood volume is a determinant of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by a decrease in effective arterial blood volume (EABV) due to either a fall in cardiac output or peripheral arterial vasodilation. The acute response to a decrease in EABV involves vasoconstriction mediated by angiotensin, sympathetic mediators, and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The resultant renal vasoconstriction limits the distal tubular delivery of sodium and water, thus maximizing the water-retaining effect of vasopressin and impairing the normal escape from the sodium-retaining effects of aldosterone. The elevated glomerular filtration rate and filtered sodium load in pregnancy allows increased distal sodium and water delivery in spite of a decrease in EABV, thus limiting edema formation during gestation.