bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood pressure levels in urban school-age population in Chile.
Authors: Norero C , Vargas N A , Mayne D , Monti A , Kutz M , Saíto R
Published: September 2013

Two blood pressure (BP) measurements separated by 3 months were performed according to international guidelines on 2976 students (11 to 19 years) of different economic levels. Obesity was defined based upon height and weight. With the first measurements, 59th and 95th percentile value distribution curves were defined. Systolic hypertension (SH) was found in 9.5%; 10.2% were males and 8.9% females. The sample showed that 8.1% were obese (240 cases); among them the incidence of SH increased to 28.8% (69 cases) (p less than 0.01). In the entire sample, diastolic hypertension (DH) was 4.3%; males, 2.7%, and females, 5.5% (p less than 0.01). Among obese students, DH increased to 8.3% (20 cases) (p less than 0.01), and showed prevalence figures of 5.8% for obese males and 10.3% (14 cases) for obese females. After a second measurement, DH for the sample decreased to 1.8%. Salt intake and familial antecedents of high BP showed differences between hypertensive and normal populations.
Release of activatable kallikrein by isolated rat kidneys.
Authors: Corthorn J , Roblero J
Published: September 2013

Rat isolated kidneys were perfused for 60 minutes with a modified Krebs-Henseleit bicarbonate solution. Perfusate and urine samples showed kininogenase activity (active kallikrein) which could be enhanced by activation with trypsin (activatable kallikrein). Identification of the kininogenase activity generated by trypsin was made with rat renal kallikrein antiserum, aprotinin, lima bean trypsin inhibitor (LBTI), soybean trypsin inhibitor (SBTI), and ovomucoid. A sample of perfusate was partially purified through DEAD-Sephacel chromatography. Intraarterial injection of this fraction decreased blood pressure in the perfused hind limb of a rat.
Urinary kallikrein and plasma renin activity in normal human pregnancy.
Authors: Valdés G , Espinoza P , Moore R , Croxatto H R
Published: September 2013

Urinary kallikrein excretion (UK), plasma renin activity (PRA), and 24-hour urine volume, sodium, and potassium excretion rates were determined sequentially in 16 normal pregnant women. Throughout gestation, UK was significantly elevated as compared to values obtained in 13 control women (1466 +/- 152 vs 375 +/- 90 U/g creatinine). The highest level was observed in Period 2 of gestation, corresponding to Weeks 17 to 24. PRA was also significantly elevated during pregnancy (11.97 +/- 1,35 vs 1.06 +/- 0.90 ng/ml/hr), with the highest level in Period 2. Mean 24-hour urine volume, sodium, and potassium excretion rates were significantly higher during pregnancy. Nor correlation was found between UK and: PRA, urine volume, and sodium and potassium excretions. These findings indicate a consistent activation of the renal-kallikrein-kinin system during pregnancy. We postulate that this vasodilator system might play a role in the maintenance of normotension in pregnancy, counteracting tha effect of the renin-angiotensin-aldosterone system.
Effects of tonin on the adrenal secretion in the rat.
Authors: Schiffrin E L , Garcia R , Gutkowska J , Lis M , Genest J
Published: September 2013

Tonin infused intravenously at a rate of 12 micron g/kg/min for 2 hours stimulated aldosterone and corticosterone secretion in conscious rats. In pentobarbital-anesthetized rats treated with dexamethasone and morphine, tonin stimulated aldosterone secretion, but corticosterone was unaffected. Tonin did not stimulate steroidogenesis in isolated rat adrenal glomerulosa cells unless substrate, in the form of "stripped" rat plasma, was added, in which case large amounts of immunoreactive angiotensin II were generated. These results suggest that tonin may generate an angiotensin peptide in vivo, which in turn stimulates aldosterone secretion. ACTH is secreted in response to tonin infusion, and contributes to the adrenal response.
Food choices for lowering sodium intake.
Authors: Altschul A M , Grommet J K
Published: September 2013

Excessive intake of dietary sodium is one form of affluent or industrial society malnutrition. When combined with a genetic-based sodium sensitivity, this high sodium intake becomes a factor in the etiology of hypertension. Most dietary sodium comes from food, natural of processed. Indirect measures of discretionary sodium intake, that from the salt shaker in the kitchen or at the table, put it at a level of 25% to 50% in the United States. Direct measures on a small sample of subjects indicate that less than 10% of sodium intake is discretionary. Anyone who needs to reduce sodium intake must, therefore, make major changes in diet. This requires information on the sodium content of common foods, the availability of low sodium analogs of popular foods, and a variety of low sodium condiments to provide more choice for the individual.
Epidemiology and genetics of hypertension.
Authors: Havlik R J , Feinleib M
Published: September 2013

The major decline in cardiovascular mortality during the last 20 years may be related to improved hypertension control, but a causal relationship has not been proven. Fundamental epidemiologic associations between age, sex, race, socioecomonic class, and blood pressure (BP) have been well characterized. Risk of coronary heart disease and stroke mortality and morbidity is linearly related to BP or to categorically defined hypertension. Weight is a major correlate of BP at all ages and in most populations. The relationships between hypertension and other nutritionally related factors are not so well defined. The Framingham Study (both cohort and offspring components) provides information about other BP correlates such as heart rate and clinical chemistry values as well as evidence suggesting a genetic influence on BP variability in families. Combined with observations from other studies, it appears that heredity plays a very important role in human hypertension.
Blood pressure trends with aging.
Authors: Kotchen J M , McKean H E , Kotchen T A
Published: September 2013

In industrialized societies, blood pressure increases with age, and blood pressure at one age is related to blood pressure at an earlier age. Blood pressure is also related to weight, weight change, and maturation. This paper reviews the association of growth and maturation with blood pressure and the evidence for blood pressure "tracking" with age. Additional longitudinal studies are required to determine if blood pressures before puberty are related to blood pressures of sexually mature young adults. Adolescents with "gestational" hypertension also have relatively high blood pressures at long-term follow-up. Thus, it may by possible to identify young individuals who are at increased risk for cardiovascular disease.
Alcohol, tobacco, and hypertension.
Authors: Friedman G D , Klatsky A L , Siegelaub A B
Published: September 2013

In many studies of diverse populations it has been found that persons drinking relatively large amounts of alcohol tend to have higher blood pressures. In the Kaiser-Permanente study of about 87,000 persons, this alcohol-blood pressure association was not attributable to demographic characteristics, adiposity, reported salt use, smoking, or coffee consumption, nor could it be explained by underreporting of alcohol consumption. If the relationship is a causal one, the pathogenesis is not yet established; direct mechanisms or the effects of withdrawal from alcohol are possible explanations. The Kaiser-Permanente data suggest that about 5% of hypertension in the general population may be due to the consumption of three or more alcoholic drinks per day. Alcohol use shows a positive relation to some sequelae of hypertension but not others; the outstanding exception is coronary heart disease which is negatively related to alcohol intake, probably through different mechanisms. In most studies, cigarette smokers have shown similar or slightly lower blood pressures than non smokers. The degree to which this is due to the thinner body build of smokers, on the average, is not well established; nor is the degree to which a stronger negative relation of smoking to blood pressure might be masked by concomitant alcohol use.
Drug and dietary intervention in hypertension.
Authors: Langford H G
Published: September 2013

Antihypertensive drug treatment has been shown to be efficacious in reducing mortality, morbidity, and end-organ damage from hypertension. However, the health care consequences of providing continued antihypertensive therapy for approximately one-fourth of the adult population has led to inquiry into the potential of nutritional change as an alternative therapy. The relapse rate for the return of hypertension after withdrawal of antihypertensive drugs is greater in the obese than in the nonobese patient. The relapse rate is also much greater if the hypertension was severe before antihypertensive drugs were started. A programmed course of dietary instruction enabled participants to drop sodium excretion by 50%, and to lose approximately 5% of body weight in 32 weeks. Adequate large-scale trials to determine the therapeutic success rate of dietary modification in mild hypertension have yet to be done. Studies have been initiated in the United States and Finland to determine the feasibility of dietary modifications as a means of preventing the occurrence of hypertension. This endeavor deserves the highest priority, for the magnitude of the problem threatens to overwhelm conventional means of provision of medical care.
RDA and related tracking systems concerned with sodium.
Authors: Forbes A L
Published: September 2013

The U.S. Food and Drug Administration (FDA) and the Department of Health and Human Services have developed a five-point set of sodium initiatives aimed at moderation of sodium consumption, improved sodium-related information for consumers and health professionals, and improved consumer choice in the marketplace. Implimentation is fundamentally based on a voluntary premise, and indications to date are that the program is working. FDA has established a series of tracking systems to measure change over time, particularly relative to changes in the sodium content of the food supply, in the sodium content of American diets, in sodium labeling -- both quantitative and qualitative, in consumer understanding of the sodium-and-hypertension problem, and in consumer food purchasing practices. Some of these efforts are conducted in cooperation with other Federal agencies such as the National Heart, Lung, and Blood Institute and the Department of Agriculture. The epidemiological approach to measurement of the prevalence of hypertensive disease as provided by the periodic National Health and Nutrition Examination Surveys is at the center of all other tracking systems to measure effectiveness of the national effort to reduce sodium intakes and thereby hopefully moderate the magnitude and severity of hypertensive disease as a major public health problem in the United States.
Reduction of blood pressure associated with dietary polyunsaturated fat.
Authors: Iacono J M , Dougherty R M , Puska P
Published: September 2013

Evidence linking the beneficial effect of dietary polyunsaturated fat on systolic and distolic blood pressure is reported. Under controlled dietary conditions, i.e., when the polyunsaturated fat to saturate fat ratio (P/S) is maintained at about 1.0, with fat providing 25% of total energy intake, blood pressure is significantly lowered in healthy males and females in the 40- to 60-year age group. The subjects selected for these studies were either normotensive or mildly hypertensive. When the subjects resumed their usual diets, their blood pressures reverted to baseline values. Body weights of the subjects remained relatively constant in these studies, and sodium chloride intakes averaged 8 to 12 g per day. It is suggested that the lowering of blood pressure by dietary linoleic acid is mediated through prostaglandins.
Obesity and hypertension: cardiovascular response of weight reduction.
Authors: Berchtold P , Jörgens V , Kemmer F W , Berger M
Published: September 2013

There is a close epidemiological association between obesity and blood pressure for all age groups, although not every obese individual becomes hypertensive. In populations without age-related increases in body weight, an elevation of blood pressure with age is not seen. Treatment of obesity by weight loss decreases blood pressure substantially; however, in a minority of patients blood pressure does not fall with weight loss. Blood pressure generally decreases before normal weight is achieved. Blood pressure after weight loss remains reduced as long as there is no marked regain of body weight. Salt intake reduction does not appear to explain why weight reduction lowers blood pressure. Reduced levels of plasma renin activity, serum aldosterone levels, catecholamine levels, and serum insulin levels may be involved in the blood pressure lowering associated with weight loss. Since the risk to the hypertensive patient is not only determined by the blood pressure, an overall treatment that aims at reduction of all risk factors is advocated. Some risk factors, e.g., glucose intolerance, may be normalized only when desirable weight is achieved. Thus, in any obese hypertensive patient with other risk factors, normalization of excess body weight appears to be the first the most important step of any rational therapeutic strategy.
Hypertension and exercise.
Authors: Björntorp P
Published: September 2013

In such a prevalent disease as hypertension, it is particularly important to examine preventive and therapeutic alternatives as changes in life-style. Repeated physical exercise (physical training) has been shown to cause blood pressure to fall in normotensives and mild hypertensives, whether obese or not. This is followed by other hemodynamic changes characteristic of reduced sympathetic nervous system activity, which can also be found in metabolic and endocrine variables. In addition, there is evidence for an increased adrenergic sensitivity after physical training in circulatory, endocrine, and metabolic variables. In lipolysis regulation, the exact adaptation is located at the GTP-binding protein level between the adrenergic receptor and the cyclase. It is indicative that physical training causes an adaptation in the central sympathetic nervous system and, secondarily, an increased sensitivity of the periphery. This might possibly explain the decreased blood pressure caused by physical training, particularly in mild hypertension where symptoms of increased sympathetic nervous system activity have been observed.
Physiologic regulation of arterial pressure. An overview.
Authors: Dustan H P
Published: September 2013

Research of the past 30 years has produced information showing the close interrelationships of neural mechanisms, the renin-angiotensin-aldosterone system, and salt balance as determinants of arterial pressure, both normal and elevated. Contemporary emphases are on central sites of neural regulation of arterial pressure, and an interesting sidelight of the conventional approaches is the possibility that the endorphin-enkephalin system may have a role in hypertension. Salt balance is critically important for people with salt-dependent hypertension; mechanisms of this dependency have not been defined but possible candidates are activation of the sympathetic nervous system, release of a natriuretic factor that causes vasoconstriction as well as salt loss, and renal-neural interactions.
Influence of cations on kinetics of angiotensin II binding to adrenal, renal, and smooth muscle receptors.
Authors: Douglas J G , Brown G , White C
Published: September 2013

A number of biological responses to angiotensin II have been demonstrated to be modulated acutely by cations, but the exact mechanism has not been elucidated. We have utilized a radioreceptor assay for angiotensin II to determine whether this acute regulatory mechanism could be related to a change in either number or affinity of angiotensin II binding to receptors. Three target tissues were used (adrenal glomerulosa, glomeruli, and uterine smooth muscle). Both mono- and divalent cations influence the kinetics of angiotensin II binding in a similar manner in all tissues. Divalent cations increase the number of receptor sites to a greater extent than did monovalent cations, while monovalent cations changed binding affinity to a greater extent than did divalent cations. These studies demonstrate that both the number and affinity to a greater extent than did monovalent cations, while monovalent cations changed binding affinity to a greater extent than did divalent cations. These studies demonstrate that both the number and affinity of angiotensin receptors can be rapidly modulated by a variety of cations.
Sulfoconjugation of catecholamines, nutrition, and hypertension.
Authors: Kuchel O , Buu N T , Serri O
Published: September 2013

Sulfoconjugation is an important metabolic pathway determining the fate and potential cardiovascular action of ingested phenolic substances. Among the three catecholamines, dopamine (DA) is to the highest degree sulfoconjugated and has the highest affinity toward the phenolsulfotransferase (PST). The concentration of some sulfated catecholamines, particularly of DA sulfate, increases following ingestion of catecholamines or their precursors. This can be confounded with blood-derived increases in DA sulfate associated with BP peaks in some hypertensive patients. We mimicked, therefore, the latter condition by infusion of free DA into normotensive subjects. At low DA infusion rates, plasma DA sulfate exceeded free DA concentrations, and there were no changes in blood pressure and pulse rate. At higher DA infusion rates, blood pressure and pulse rate increased only while plasma free DA concentrations exceeded those of DA sulfate, indicating that free DA remains biologically active only prior to being conjugated. A similar increase in DA sulfate from alimentary sources (e.g., eating a banana) remains without cardiovascular response and is not associated with an overflow of free DA, since all the ingested DA is conjugated in the gut. We describe a patient with pheochromocytoma who experienced repeated hypertensive crises after ingestion of food containing some biogenic amines, (once also documented by NE increase), possibly due to a phenol sulfoconjugation defect (e.g., substrate inhibition of the PST or its genetic deficiency). Platelet PST-determinations may serve as a screening tool to detect subjects with sulfoconjugation defects since they probably reflect the PSt activity in the gut where ingested phenols are sulfoconjugated.
Vascular changes in DOCA hypertension. Influence of a low protein diet.
Authors: Moreland R S , Webb R C , Bohr D F
Published: September 2013

The goal of this study was to characterize the influence of low protein diet on vascular changes induced by deoxycorticosterone acetate (DOCA) hypertension. DOCA hypertensive and control normotensive rats were placed on a low protein (5%) diet for 4 weeks. This intervention blocked the further increase in systolic blood pressure of rats treated with DOCA; systolic blood pressures of control rats were not influenced by the low protein diet. The sensitivity of isolated mesenteric arteries to norepinephrine was increased in DOCA hypertensive rats compared to that in arteries from control rats; arterial strips from rats maintained on the low protein diet were less sensitive to the catecholamine than arteries from their respective control diet group. Vascular sensitivity to calcium was identical in both normotensive and DOCA hypertensive rats, and the low protein diet had no effect on this measure of calcium activation. Calcium-induced relaxation was depressed in arteries from DOCA hypertensive rats, suggesting a decreased stabilizing influence of the cation on the excitable membrane. Arteries from rats maintained on the low protein diet showed enhanced relaxation to calcium compared to those from their respective control diet group. Membrane stores of calcium available for activation by norepinephrine were increased in arteries from DOCA hypertensive rats; the low protein diet decreased the storage capacity of these membrane sites. The total protein content of the aorta was increased in DOCA hypertensive rats and depressed to control level in DOCA rats maintained on low protein diet. No change was observed in actomyosin content nor in the actin-to-myosin ratio during the DOCA hypertension or the addition of a low protein diet. Since one action of DOCA is to increase cellular protein synthesis, the attenuation of these vascular changes in DOCA rats maintained on a protein-deficient diet is probably due to a decrease in available substrate.
Endothelial mechanism in the vascular action of hydralazine.
Authors: Spokas E G , Folco G , Quilley J , Chander P , McGiff J C
Published: September 2013

Relaxation of precontracted isolated chains of aortic rings with intact endothelium and in those with the endothelium removed was studied in response to various antihypertensive vasodilator drugs. Of the drugs tested--nitroprusside, nitroglycerin, prazosin, minoxidil, diazoxide and hydralazine--only the vascular relaxant effects of hydralazine were found to be dependent, in part, on the presence of intact endothelium. The endothelial component of the hydralazine response represented a major contribution to the net relaxant effect on the vascular smooth muscle, particularly at lower concentrations, 90 nM to 1 microM, which are also clinically relevant.
Cardiovascular effects of antihypertensive polar and neutral renomedullary lipids.
Authors: Muirhead E E , Folkow B , Byers L W , Desiderio D M , Thorén P , Göthberg G , Dow A W , Brooks B
Published: September 2013

Two antihypertensive lipids can be extracted from fresh renal medulla. One is polar (the antihypertensive polar renomedullary lipid, or APRL) and the other is nonpolar (the antihypertensive neutral renomedullary lipid, or ANRL). APRL and ANRL differ in their biologic activities: APRL in bolus intravenous injections causes a very rapid decline in the arterial pressure (AP) while ANRL, after a lag of 2 minutes, causes a slower decline in AP. APRL increases heart rate and sympathetic activity. ANRL decreases heart rate and sympathetic activity. ANRL appears to convert to APRL, under certain in vitro circumstances, suggesting that the structure of the two molecules is related. ANRL and APRL appear in the renal venous effluent after unclipping; biologically, ANRL seems dominant. The renal venous effluent of the unclipped isolated kidney lowers the HR and sympathetic activity of the normal rat. Unclipping degranulates the renomedullary interstitial cells (RIC). The antihypertensive effect of unclipping appears due to the secretion of ANRL and APRL by the kidney. It is concluded that ANRL seems to be the antihypertensive hormone of the RIC.
Development of a new strain of spontaneously hypertensive rats homozygous for hypothalamic diabetes insipidus.
Authors: Ganten U , Rascher W , Lang R E , Dietz R , Rettig R , Unger T , Taugner R , Ganten D
Published: September 2013

The aim of the present study was to investigate whether the presence of arginine vasopressin (AVP) is necessary for the establishment of high blood pressure in spontaneously hypertensive rats (SHR). For this purpose we crossbred SHR of the stroke-prone substrain (SHRSP) with rats homozygous for hypothalamic diabetes insipidus of the Brattleboro strain (DI) which are unable to synthetize AVP. The successful introduction of the DI gene into the SHRSP strain (SHRDI) was demonstrated by the following observations: In 10-month-old rats, water intake was similarly elevated in SHRDI as in DI rats (137 +/- 6.5 vs 125 +/- 10.5 ml per 24 hours). AVP was undetectable in the plasma, in the hypothalamus, and in the pituitary of SHRDI and DI rats. Urine osmolality and urinary concentration of sodium and potassium were markedly reduced. SHRDI and DI did not adequately concentrate their urine during an 8-hour period of water deprivation, but both strains of rats responded well with a fall in urine output and a rise in urine osmolality to subcutaneous administration of the non-pressor analog of AVP, DDAVP. Mean arterial blood pressure was markedly increased in SHRDI as well as in SHRSP (184 +/- 9.7 vs 197 +/- 5.2 mm Hg). Thus, we have developed a new line of spontaneously hypertensive rats homozygous for hypothalamic diabetes insipidus. From this finding it is concluded that AVP is not essential for the development and maintenance of spontaneous hypertension of rats.
Alterations in plasma and cerebrospinal fluid norepinephrine and angiotensin II during the development of renal hypertension in conscious dogs.
Authors: Suzuki H , Ferrario C M , Speth R C , Brosnihan K B , Smeby R R , de Silva P
Published: September 2013

The levels of norepinephrine (NE), epinephrine (E), and angiotensin II immunoreactivity (AIIir) in plasma and in cerebrospinal fluid (CSF) were measured in eight conscious dogs before and during a 28-day period in the development of two-kidney, one clip (2K1C) hypertension produced by a two-step procedure. The early phase (less than 7 days) of hypertension following partial constriction of the renal artery was accompanied by tachycardia and increases in concentrations of NE and AIIir in both plasma and CSF; E did not change. One week later blood pressure remained elevated (107 +/- 2 after vs 88 +/- 2 mm Hg before clipping, p less than 0.05), but other variables returned to control values. Occlusion of the partially constricted renal artery caused severe hypertension that was initially associated with a transient decrease in levels of NE in both plasma and CSF and a sustained rise in plasma and CSF concentrations of AIIir that persisted for as long as 2 weeks after the second operation. None of these effects was seen in nine sham-operated dogs. Since activation of the renal pressor system is associated with time-related changes in the concentrations of NE and AII in both plasma and CSF, these observations indicate early involvement of both sympathetic and renin-angiotensin systems in the pathogenesis of renovascular hypertension.
Increased vascular sensitivity to angiotensin ii in psychosocial hypertensive mice.
Authors: Webb R C , Johnson J C , Vander A J , Henry J P
Published: September 2013

CBA mice develop hypertension when placed in complex population cages that facilitate social interactions and competition for territory. After 1 month, these mice have normal plasma renin levels, but blockade of converting enzyme lowers blood pressure to normal. To test the possibility that this normal-renin hypertension is caused by enhanced pressor responsiveness to angiotensin II (AII), we examined the effects of AII on hindquarter and renal vasculatures from 13 hypertensive and 13 normotensive mice. Both vascular beds were pump-perfused at a constant flow with plasma substitute. Optimal perfusion flows and basal pressures were similar in hindquarter (8 ml/100 g/min; 60 mm Hg) and renal vasculatures (130 ml/100 g/min; 50 mm Hg) from normotensive and hypertensive mice. Threshold constrictor responses to AII were elicited at a significantly lower dose in both vasculatures of hypertensive mice than in those of normotensive mice. Maximal pressor responses to AII were greater in the hindquarters of hypertensive mice than in those of normotensive mice, but were not different in the renal vasculatures of the two groups. Vasoconstrictor sensitivity to norepinephrine was also increased in the hindquarters of hypertensive mice; however, the changes in threshold and maximal pressor response were less than for AII. Responsiveness to norepinephrine in the renal vasculatures of hypertensive mice was not different from that in the kidneys of normotensive mice. We conclude that the hyperresponsiveness to AII in the resistance vessels plays an important role in maintaining elevated blood pressure in this psychosocial model of hypertension.
Vasoactive peptides. State-of-the-art review.
Authors: Said S I
Published: September 2013

At least 16 naturally occurring peptides either constrict or dilate blood vessels. Many of these peptides are present in nerve cells and nerve terminals supplying systemic and pulmonary blood vessels and the heart. Such neuropeptides are released locally as neurotransmitters, and can influence vascular tone, local and regional blood flow, arterial blood pressure, and cardiac function. There is evidence for the participation of at least some vasoactive peptides in the regulation of these functions and in the mediation or modulation of systemic shock and arterial hypertension. The investigation of vasoactive peptides in relation to cardiovascular function and dysfunction is at a promising threshold.
Relationship of alpha receptor types to hypotension and renal vasodilation caused by alpha blockers in conscious dogs.
Authors: Zimmerman B G , Largent R D
Published: September 2013

In conscious instrumented normotensive and two-kidney, one clip Goldblatt hypertensive dogs, we compared the effects of the alpha-receptor blocking agent, urapidil, on blood pressure, renal vascular resistance, heart rate, and plasma renin activity with those of prazosin and phentolamine. Urapidil (2 mg/kg) and prazosin (0.25 mg/kg) decreased blood pressure and renal vascular resistance in both groups of animals, and urapidil caused a small increase in renal blood flow. Heart rate, but not plasma renin activity, was increased at the peak of the hypotension. Phentolamine had no significant effect on any of these parameters. All three agents markedly inhibited the renal vasoconstrictor responses to intraarterially administered phenylephrine and norepinephrine, and thus exhibited an alpha 1-receptor blocking action. Only urapidil significantly antagonized the response to B-HT 933, a selective alpha 2-receptor agonist, indicating that it also interacts at alpha 2-receptor sites. Since both normotensive and hypertensive animals exhibited similar hypotensive responses after both urapidil and prazosin, the degree of alpha-receptor blockade achieved did not reveal greater sympathetic tone in renal hypertension.
A paradigm for identification of primary genetic causes of hypertension in rats.
Authors: Rapp J P
Published: September 2013

A paradigm is developed for identifying the genes (and the biochemical-physiological traits for which the genes code) that cause differences in blood pressure in inbred strains of rats. A biochemical-physiological trait which meets the following four criteria is one which can reasonably be accepted as causing genetic differences in blood pressure: 1) a difference in a biochemical or physiological trait between two strains must be demonstrated; 2) the trait must be shown to follow Mendelian inheritance; 3) the genes identified in criterion 2 must co-segregate with an increment in blood pressure which is significantly different from zero; and 4) there must be some logical biochemical and/or physiological link between the trait and blood pressure. Traits which do not show discrete phenotypes following Mendelian inheritance may correlate with blood pressure in segregating populations. In this case no rigorous cause and effect genetic argument is possible because such correlations could arise from complex primary genetic causes or as secondary effects of blood pressure on the biochemical-physiological trait.
Development and preliminary application of a new assay for aldosterone stimulating factor.
Authors: Sen S , Bumpus F M , Oberfield S , New M I
Published: September 2013

A new assay method has been developed to measure aldosterone stimulating factor (ASF) quantitatively. This method utilizes a combination of affinity chromatography and high pressure liquid chromatography (HPLC). Antibodies raised against ASF, coupled to Affi-Gel 10, were used as the affinity column, and adsorbed ASF was eluted with 4 M urea. Quantitation was based on the external standard method of analysis using the area of the standards as controls, which were previously tested by HPLC for purity. The amount of ASF in the unknown samples was calculated on the basis of the area of the peak emerging at the retention time of ASF. A parallel bioassay using adrenal glomerulosa cells was also done to assess the biological activity. In eight normal volunteers, the urinary ASF was 146 +/- 4.6 ng/24 hr urine, whereas in plasma it was 70.5 +/- 6.5 ng/100 ml. The method is reproducible, specific for ASF, and showed less than 3% inter- or intraassay variability. In a preliminary study, when ASF was quantified from the 24-hour urine of two patients with adrenal hyperplasia, a significantly higher level of ASF was found (750 and 1020 ng/24 hr urine). These data suggest that ASF may be of pathological significance in certain hypertensive patients, especially in the hypertension associated with hyperaldosteronism.
The possible biological role of aldosterone metabolites.
Authors: Morris D J , Kenyon C J , Latif S A , McDermott M , Goodfriend T L
Published: September 2013

Following the incubation of aldosterone with microsomes from liver of adrenalectomized male rates, a previously unidentified polar neutral metabolite of aldosterone, designated "peak A" material, was isolated and purified using high pressure liquid chromatography. This peak A material, which contains a reduced hydroxylated metabolite of aldosterone, was shown to possess 2% to 3.5% of the mineralocorticoid activity relative to aldosterone. When bovine adrenal glomerulosa cells were incubated with peak A material (3 and 10 micrograms/ml), the binding of 125I-angiotensin II was inhibited by 20% and 36%, respectively. The mineralocorticoid activity of the six possible ring A reduced metabolites was tested. The 5 alpha-reduced metabolites were more potent than the 5 beta-, and the 3 alpha- were more potent than the 3 beta-reduced metabolites. The renal and extrarenal transformations of aldosterone to the polar and nonpolar (reduced) metabolites and their possible role in the accepted mechanism of action of aldosterone is discussed.
Calcium blockade in arterial hypertension. Review.
Authors: Lederballe Pedersen O
Published: September 2013

The use of calcium blockers in arterial hypertension is based on experimental evidence for an altered role of calcium (Ca++) in hypertensive vascular smooth muscle and enhanced vasodilatatory effects of these drugs in the hypertensive organism. Both verapamil and nifedipine reduce blood pressure acutely and on chronic administration. Acute administration results in reflex-activated increments of heart rate, plasma renin activity, and plasma catecholamines after nifedipine, whereas these effects are less conspicuous after verapamil. Acute diuretic, natriuretic, and uricosuric effects can be demonstrated. On repeated administration of nifedipine, a degree of tolerance develops and on long-term administration it may be necessary to combine it with a beta-adrenoceptor blocker and a diuretic. In animal experiments, calcium blockers have shown favorable effects on hypertensive cardiovascular structural changes, but such unique beneficial effects remain to be demonstrated in the human disease.
Treatment of hypertension with calcium antagonists. Review.
Authors: Guazzi M D , Polese A , Fiorentini C , Bartorelli A , Moruzzi P
Published: September 2013

Calcium channel blockers have a selective action on the cardiovascular system. They reduce the energy requirement of the heart, reduce vascular smooth muscle tone, and increase systemic blood flow. Vasodilatation occurs in both the systemic and the pulmonary systems to an extent proportional to the baseline level of vascular resistance, and results in reduction of blood pressure when it is elevated. Thus, these blockers are useful in patients with high blood pressure. Clinical experience of calcium channel blockers in hypertension is so far confined almost exclusively to verapamil and nifedipine. This article reviews the advantages and limitations of these two compounds, their acute hemodynamic effects in hypertensive subjects, and their use in the treatment of hypertensive emergencies, hypertensive encephalopathy, and pheochromocytoma, and as ventricular afterload reducing agents in hypertensive left ventricular failure. Similarities in the effects of nifedipine on systemic and pulmonary vascular tone are presented as evidence that altered intracellular Ca++ concentration is involved in the vasoconstriction seen in both systems in systemic high blood pressure. They also provide support for the hypothesis that inappropriate Ca++ handling may be involved in maintaining elevated blood pressure in human hypertension.
Nifedipine or verapamil as sole treatment of hypertension. An intraarterial study.
Authors: Gould B A , Hornung R S , Mann S , Subramanian V B , Raftery E B
Published: September 2013

Intraarterial ambulatory blood pressures were recorded prior to and during therapy with two different calcium ion antagonists, nifedipine and verapamil, in two separate groups of patients. In the first group, nine patients were studied off therapy and following a minimum of 6 weeks of nifedipine treatment (dose range, 20 to 60 mg twice daily). A second group of 16 patients followed the identical protocol but were prescribed verapamil (120 to 160 mg, three times daily). During both studies, patients underwent standardized physiological tests including tilt, isometric handgrip, and dynamic bicycle exercise. Both verapamil and nifedipine caused a reduction in blood pressure over most of the 24 hours studied. Nifedipine did not affect heart rate whereas verapamil caused a reduction of approximately 10 bpm. Nifedipine and verapamil did not induce postural hypotension, and the absolute responses to dynamic and isometric exercise were reduced. These results show the efficacy of slow channel inhibitors in the management of essential hypertension.
Management of hypertensive crises.
Authors: Ledingham J G
Published: September 2013

Malignant hypertension still constitutes a medical emergency, particularly when complicated by renal failure, encephalopathy, or left ventricular failure. A shift to the right of the autoregulatory curve of cerebral blood flow (and probably of renal blood flow) is known to occur in patients with hypertension. Local cerebral edema, complicating the malignant phase, is likely to aggravate this trend. While inadequate or tardy treatment leads to encephalopathy, renal and cardiac failure, over aggressive treatment may also result in damage to brain, heart, and kidney. Recent reports of neurological damage, sometimes fatal, following aggressive hypotensive treatment suggests the need for a reappraisal of current practices. More investigation is needed to determine the effects of the various classes of antihypertensive drugs on organ perfusion, particularly of brain, heart, and kidney, in both normal and hypertensive humans. Other hypertensive crises include raised arterial pressure in association with acute dissection of the aorta and in the presence of stroke or subarachnoid hemorrhage. While there is agreement about the need for urgent hypotensive treatment in patients with aortic dissection, there is no information with which to base rational decisions in the management of high arterial pressure in the acute phase of stroke or subarachnoid hemorrhage.
Effects of antihypertensive therapy on serum lipoproteins.
Authors: Weidmann P , Gerber A , Mordasini R
Published: September 2013

Several drugs used for standard antihypertensive therapy may also interact with the lipoprotein metabolism. The following has been observed after 1 to 12 months of treatment. Various thiazide-type diuretics may significantly increase the potentially atherogenic serum low-density-lipoprotein cholesterol (LDL-C) and/or very-LDL-C-fractions, while the antiatherogenic high-density-lipoprotein cholesterol (HDL-C) is largely unchanged. Certain loop-diuretics also increase the LDL-C/HDL-C ratio and both types of diuretics elevated serum triglycerides (Tg) in some but not all studies. LDL-C was increased in diuretic-treated men and in chlorthalidone-treated postmenopausal women, but not in chlorthalidone-treated premenopausal women. The latter may be protected from this effect. Only two diuretics evaluated, namely indapamide and spironolactone, had no apparent influence on lipoproteins. Beta-blocker monotherapy may often increase Tg and slightly decrease HDL-C. The magnitude of these changes did not distinctly differ between highly cardioselective and nonselective beta-blockers, but it was less pronounced on beta-blockers than on those without intrinsic sympatholytic activity. Other sympatholytics such as reserpine, methyldopa, clonidine, debrisoquine, the alpha-beta-blocker labetalol, or the postsynaptic alpha-blocker, prazosin, did not affect or even slightly decrease Tg or total C, LDL-C, and very-LDL-C values. With combinations, a tendency for increased Tg and lower HDL-C was also apparent during thiazide-type diuretic-beta-blocker therapy. However, diuretic-induced increases in LDL-C were prevented or reversed by concomitant beta-blockade, but not by reserpine, methyldopa, or clonidine. Monotherapy with the potent direct vasodilator, carprazidil, improved blood pressure and significantly increased HDL-C. Prospective long-term studies are needed to clarify the course and the pathogenic and prognostic relevance of lipoprotein changes induced by certain diuretics or beta-blockers.
Long-term antihypertensive therapy with captopril.
Authors: Groel J T , Tadros S S , Dreslinski G R , Jenkins A C
Published: September 2013

Most forms of hypertension require life-long treatment; thus, it is important to determine the continuing effectiveness and safety of any new therapeutic agent. While participating in various investigational studies, 7103 hypertensive patients received captopril, of whom 4397 were treated for 3 months to 4 years. The 4-year patients included 2498 with mild or moderate essential hypertension (diastolic pressure less than 120 mm Hg), 893 with severe essential hypertension, and 517 with renovascular hypertension. Repeated examinations of these long-term therapy patients, the majority of whom also were receiving a diuretic, indicated no drug tolerance to the combination, i.e., there was continuing control of the blood pressure without significant increases in dosage or addition of other drugs. Side-effects occurring during the first few months of captopril administration (rash, taste disturbances, and, rarely, neutropenia) were not a problem during prolonged therapy. A few patients (70/7,103, or 1.0%) developed proteinuria, usually reversible and seldom associated with any deterioration of renal function. The proteinuria occurred most often in patients who had preexisting renal disease and were receiving high doses of the drug. There were no significant changes in key biochemical parameters. A total of 230 patients discontinued treatment for failure to maintain adequate blood pressure reduction, and 397 for side-effects. The estimated 4-year cumulative frequency of drug discontinuance for side-effects was 11.6% (life table method), which compares favorably with other classes of antihypertensive drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of captopril on renal hemodynamics in the treatment of resistant renal hypertension.
Authors: Björck S , Herlitz H , Nyberg G , Granerus G , Aurell M
Published: September 2013

The effects of 6 weeks of treatment with captopril on the renal hemodynamics of 16 patients with treatment-resistant renal hypertension (six had diabetic nephropathy, seven had other renal parenchymatous disease, and three had renovascular disease) were studied. Significant changes in glomerular filtration rate, filtration fraction, plasma renin activity, urinary aldosterone, and mean blood pressure were noted in the patients with renal parenchymatous disease, but not in those with diabetic nephropathy. Renal blood flow remained unchanged in all patients. Captopril was well tolerated.
Hemodynamic and humoral interactions between captopril and nifedipine.
Authors: Stornello M , Di Rao G , Iachello M , Pisani R , Scapellato L , Pedrinelli R , Salvetti A
Published: September 2013

Nine patients with uncomplicated essential hypertension received, according to a randomized sequence, captopril (25 mg three times daily), nifedipine (10 mg three times daily), and both drugs for 1 week, with each treatment period separated by a 1-week interval during which a placebo was given. Captopril significantly reduced blood pressure and plasma aldosterone, increased plasma renin activity (PRA), and did not change heart rate. Nifedipine exerted a similar effect on blood pressure and PRA, but it increased heart rate and did not change aldosterone. Captopril plus nifedipine further reduced blood pressure and increased PRA, did not change heart rate, and reduced aldosterone to values similar to those after captopril alone. The hypotensive effect of captopril was highly predictable by basal PRA values, and that of nifedipine by age, while PRA increments induced by captopril were unrelated to those induced by nifedipine. These data indicate that: 1) captopril and nifedipine exert an additive effect on blood pressure and renin; 2) captopril counteracts the heart rate increase induced by nifedipine; 3) nifedipine does not influence the aldosterone inhibition induced by captopril. It is suggested that the association of the two drugs can be usefully employed in the treatment of hypertension.
Effect of reducing elevated blood pressure on cerebral circulation.
Authors: Gifford R W
Published: September 2013

Circulation to the brain is protected not only by autoregulation, which maintains cerebral blood flow (CBF) in spite of a decrease in mean arterial pressure, but also by baroreflexes that tend to prevent or minimize hypotension. Hypertensive patients have impaired cerebral autoregulation and depressed baroreflex sensitivity, suggesting that the brain might be vulnerable to a reduction in blood pressure. Nevertheless, in clinical experience, studies of cerebral blood flow during drug-induced reduction of elevated blood pressure have shown that control of hypertension can usually be achieved without jeopardizing cerebral blood flow or inducing signs and symptoms of cerebral ischemia, even in patients with cerebrovascular disease. Indeed, control of hypertension reduces both the risk of stroke and the recurrence rate for second strokes.
Adrenergic vasoconstriction as a cause of inadequate hypotensive response to beta-adrenergic blockade.
Authors: Birkenhäger W H , DeLeeuw P W
Published: September 2013

This overview is concerned with the causes of nonresponsiveness to the hypotensive action of beta-adrenergic blocking drugs. The overall hemodynamic response, i.e., a secondary decrease in peripheral vascular resistance, is unrelated to the primary decrease in cardiac output. The reduction in vascular resistance may be triggered by mechanisms residing in the central nervous system, the arterial baroreceptor area, or the prejunctional beta-receptor. None of these mechanisms seem to be entirely responsible. Studies in responders vs nonresponders tend to equate nonresponsiveness with alpha-adrenoceptor-mediated vasoconstriction. Although circulating catecholamines are relatively poor indices of sympathetic activity, studies focusing on the renal-neural area appear to show clearly differential profiles between responders and nonresponders. Such findings, in relation to experimental data on the renal nerves as selective neural amplifiers, may provide a renewed interpretation of the centrally mediated hypotensive mechanism of beta-adrenergic blockade.