bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of angiotensin II antagonism on canine renal sympathetic nerve function.
Authors: Wong P C , Hart S D , Timmermans P B
Published: June 2012

The objective of this study was to examine effects of nonpeptide angiotensin II (Ang II) receptor antagonists on renal vasoconstrictor responses to renal nerve stimulation (RNS) and intrarenal injection of norepinephrine in pentobarbital-anesthetized dogs. The subtype 1-selective Ang II receptor antagonists, DuP 753 (2-n-butyl-4-chloro-5-(hydroxymethyl)-1-[(2'-(1H- tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole, potassium salt) and EXP3174 (2-n-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl) biphenyl-4-yl)methyl]imidazole-5-carboxylic acid) given intra-arterially to the kidney caused dose-dependent reductions of renal vasoconstrictor responses to RNS but not to norepinephrine. In contrast, the subtype 2-selective Ang II receptor specific ligand, PD 123177 (1-[(4-amino-3-methylphenyl)methyl]-5-(diphenylacetyl)-4,5,6,7- tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid), did not alter the renal vasoconstrictor responses to RNS, norepinephrine, and Ang II in doses of 10-100 micrograms/kg/min i.a. Captopril also reduced the renal vasoconstrictor responses to RNS but not to norepinephrine. However, saralasin did not alter the renal vasoconstrictor responses to RNS and norepinephrine, although it was as effective as DuP 753 and EXP3174 in blocking the renal vasoconstrictor response to Ang II. These results suggest that endogenous Ang II enhances renal adrenergic function at the prejunctional site in anesthetized dogs. Analogous to the Ang II receptor in vascular smooth muscle, the prejunctional Ang II receptor appears to be of subtype 1. Mechanisms accounting for the absence of the inhibition of Ang II-mediated renal adrenergic response by saralasin remain to be determined.
Chronic treatment with tin normalizes blood pressure in spontaneously hypertensive rats.
Authors: Escalante B , Sacerdoti D , Davidian M M , Laniado-Schwartzman M , McGiff J C
Published: June 2012

We have reported that short-term treatment of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats with stannous chloride (SnCl2), which selectively depletes renal cytochrome P450, restores blood pressure to normal in young but not in adult SHR, and is without effect on blood pressure of either young or adult WKY rats. We report in the present study that chronic treatment with SnCl2, begun at age 5 weeks, prevented the development of hypertension in SHR over a period of 15 weeks at which time they were killed. Suspension of SnCl2 treatment after 8 weeks (i.e., at age 13 weeks) did not result in return of blood pressure to hypertensive levels in SHR. Age-matched WKY rats were not affected by tin treatment. These findings provide additional evidence that administration of tin, which stimulates heme oxygenase, thereby producing depletion of cytochrome P450, restores blood pressure to normal levels in SHR.
Purification of an endogenous digitalislike factor from human plasma for structural analysis.
Authors: Ludens J H , Clark M A , DuCharme D W , Harris D W , Lutzke B S , Mandel F , Mathews W R , Sutter D M , Hamlyn J M
Published: June 2012

In previous reports, we described the isolation and characterization of an endogenous digitalislike factor (EDLF). In this report, we describe a unique combination of bioassay and large-scale purification methodology that made possible the purification of sufficient quantities of this inhibitor of Na+,K(+)-ATPase for structural analysis. Using an initial XAD-2 extraction and preparative high-performance liquid chromatography followed by a batch enzyme affinity extraction and two subsequent semipreparative chromatographic steps, 300 l of human plasma was processed, yielding 31 micrograms (53 nmol) of pure EDLF and representing purification on a dry weight basis in excess of 0.6 billionfold. Four divergent pieces of evidence, including chromatographic, mass spectrometric, immunoreactive, and binding characteristics, suggested that the EDLF purified in the present study was either ouabain or an isomer of ouabain. This material may represent a plasma-borne, naturally occurring, selective, high-affinity ligand for the digitalis binding site that may play a significant role in the modulation of the sodium pump and thereby cellular electrolyte homeostasis in humans.
Cellular ions in hypertension, diabetes, and obesity. A nuclear magnetic resonance spectroscopic study.
Authors: Resnick L M , Gupta R K , Bhargava K K , Gruenspan H , Alderman M H , Laragh J H
Published: June 2012

To investigate the cellular basis linking hypertension, non-insulin-dependent diabetes mellitus (NIDDM), and obesity, we used 31P and 19F nuclear magnetic resonance spectroscopy to measure intracellular pH (pHi), free magnesium (Mgi), and cytosolic free calcium (Cai) in erythrocytes of obese and NIDDM subjects with and without hypertension. Compared with normotensive, nondiabetic controls (Cai, 25.2 +/- 1.4 nM; Mgi, 232 +/- 8 microM), Cai was elevated in both normotensive (36.8 +/- 2.7 nM, sig = 0.005) and hypertensive (43.4 +/- 2.9 nM, sig = 0.001) NIDDM subjects, and Mgi was concomitantly suppressed (normotensive: 206 +/- 11 microM, sig = 0.05; hypertensive: 196 +/- 8 microM, sig = 0.001). Similar but less striking changes were noted in obese subjects. Values of pHi were significantly lower (sig = 0.05) in all hypertensive groups compared with their normotensive controls. Continuous relations were observed for all subjects between Cai and diastolic blood pressure (r = 0.649, p less than 0.001) and body mass index (r = 0.565, p less than 0.001), between Mgi and diastolic blood pressure (r = -0.563, p less than 0.001) and fasting blood glucose (r = -0.580, p less than 0.001), and in diabetics, between pHi and diastolic blood pressure (r = -0.680, p less than 0.001). Thus, the constellation of elevated Cai and suppressed Mgi and pHi levels is characteristic of the hypertensive state. These abnormalities of cellular ion handling in whole or in part common to hypertension, diabetes, and obesity may contribute to the pathophysiology of these syndromes and may help to explain their frequent clinical coexistence.
Plasma immunoreactive endothelin-1 in experimental malignant hypertension.
Authors: Kohno M , Murakawa K , Horio T , Yokokawa K , Yasunari K , Fukui T , Takeda T
Published: June 2012

We measured plasma concentrations of immunoreactive endothelin-1 (irET-1) in the prehypertensive and hypertensive phases in spontaneously hypertensive rats (SHR) and in malignant hypertension caused by deoxycorticosterone acetate (DOCA)-salt administration in SHR. We also measured concentrations of this peptide in another model of malignant hypertension, the two-kidney, one clip (2K1C) renovascular hypertensive rats chronically given caffeine. Plasma irET-1 concentrations in young (6-week-old) and mature (18-week-old) SHR did not differ from those of age-matched Wistar-Kyoto (WKY) rats. Four weeks of treatment with DOCA-salt increased blood pressure, blood urea nitrogen, serum creatinine, and plasma irET-1 in SHR but not in WKY rats. Eight weeks of DOCA-salt treatment further increased these values in SHR. Plasma irET-1 concentrations were not increased in the 2K1C rats. Six weeks of caffeine administration increased blood pressure, blood urea nitrogen, serum creatinine, plasma renin activity, and plasma irET-1 in the 2K1C rats but not in the sham-operated rats. High-performance liquid chromatographic profiles of plasma extracts pooled from these rats with malignant hypertension showed that a major component of irET-1 eluted in the position of synthetic ET-1 (1-21). Furthermore, acute hypertension induced by angiotensin II or phenylephrine did not affect the plasma irET-1 concentration in rats. The results suggested that the plasma ET-1 concentration is increased in rat models of malignant hypertension and that the high blood pressure itself is not the main factor involved in the increase of plasma ET-1.
Diagnostic usefulness of renal scanning after angiotensin converting enzyme inhibitors.
Authors: Davidson R , Wilcox C S
Published: June 2012

Radioisotopic renal scanning after angiotensin converting enzyme inhibition (ACEI) has proven to be an exciting area for research. The biologic activity of markers such as DTPA and hippuran, when combined with the physiological effects of ACEI, may provide noninvasive methods of diagnosing both renal artery stenosis and renovascular hypertension. Recent investigators have demonstrated that the sensitivities and specificities of these tests may vary widely; these differences are probably due to variations in study design, patient population, diagnostic criteria, and outcome measurements. We have reviewed these studies and discuss these possible sources of variation and their impact on the clinical usefulness of these diagnostic tests, especially in relation to the prevalence of disease in the population. Current results suggest that the post-ACEI DTPA scan is relatively accurate in the diagnosis of renal artery stenosis, with sensitivity generally greater than 90% and specificity around 95%. However, the best results in predicting the response to angioplasty or surgery in patients with renal artery stenosis have been with the use of post-ACEI hippuran in combination with furosemide (sensitivity, 96%; specificity, 95%). With confirmation of these findings and continued investigation, it is expected that accurate noninvasive tests will be available for widespread clinical use in the near future.
Structure, expression, and regulation of the murine renin genes.
Authors: Sigmund C D , Gross K W
Published: June 2012

It has long been known that the renin-angiotensin system plays an integral role in the regulation of blood pressure and electrolyte and fluid balance in mammals. The advent of molecular biologic techniques has afforded new insights into the genes regulating blood pressure. Laboratory mice and rats have been used as experimental models to examine the structural organization and expression of the renin gene. It is now well established that some mice, unlike rats and humans, contain a duplicated copy of the renin locus, which accounts for the high level of renin activity long known to be found in the submandibular gland of some mice. Indeed it is this fortuitous observation that facilitated the isolation of the first complementary DNA clones for renin and ultimately the many species-specific probes now available to analyze mammalian tissues for evidence of primary renin expression. The use of complementary DNAs as probes for primary renin expression helped confirm and further clarify earlier studies demonstrating the presence of renin activity in a number of extrarenal tissues. Although expression in some of these tissues is evolutionarily conserved, their significance has still been elusive. In this report we review the impact of molecular biology on our current understanding of renin gene structure and organization, tissue- and cell-specific expression and regulation, and the changes in renin expression throughout ontogeny. In addition, we describe how new developments in gene transfer technology have added important tools to our arsenal for examining renin gene regulation and how these technologies can be used to develop new tools for renin and hypertension research.
Deuterium oxide prevents hypertension and elevated cytosolic calcium in hypertensive rats.
Authors: Vasdev S , Sampson C A , Longerich L , Parai S
Published: June 2012

Increased calcium uptake in vascular tissue, leading to elevated cytosolic free calcium, has been implicated in the pathophysiology of hypertension. This study examined the dose-dependent effect of deuterium oxide (5%, 10%, or 20% in drinking water) on systolic blood pressure, aortic calcium uptake, and platelet cytosolic free calcium in spontaneously hypertensive rats. Starting at age 8 weeks, spontaneously hypertensive rats were divided into four groups of six animals each. The drinking water of groups 1, 2, 3, and 4 was replaced by 100% water and 5%, 10%, and 20% deuterium oxide in water, respectively, for another 7 weeks. Ten Wistar-Kyoto rats, age 8 weeks, were given 100% water for the next 7 weeks. The usual increase in systolic blood pressure and the associated increase in aortic calcium uptake and platelet cytosolic free calcium in spontaneously hypertensive rats at age 15 weeks was lowered in a dose-dependent manner by deuterium oxide. Deuterium oxide also prevented renal vascular changes in spontaneously hypertensive rats. A minimum dose of 10% deuterium oxide was needed to completely prevent the development of hypertension, elevated aortic calcium uptake, platelet cytosolic free calcium, and renal vascular changes in spontaneously hypertensive rats.
Effect of regular exercise on 24-hour arterial pressure in older hypertensive humans.
Authors: Seals D R , Reiling M J
Published: June 2012

The experimental goals were to determine if regular low-intensity aerobic exercise reduces 24-hour arterial blood pressure in middle-aged and older (aged 50 years or older) humans with mild diastolic (90-105 mm Hg) essential hypertension and, if so, whether this is accurately reflected by changes in casual recordings made at rest. Fourteen subjects walked 3-4 days/wk for 6 months, with 10 exercising an additional 6 months; 12 other subjects served as nonexercising controls. In the exercising subjects, maximal oxygen consumption increased 7-14% (p less than 0.05) with little or no change in body weight or fat. Conventional casual readings of systolic, mean, and diastolic arterial pressure at rest were lower (5-10 mm Hg, p less than 0.05) in all body positions after 6 months of exercise and changed little thereafter. Casual recordings made during additional circulatory measurements showed 6-month decreases of only half this magnitude and were specific to a particular blood pressure phase and body position; however, all changes were significant after 12 months of exercise. The reductions in arterial pressure at rest were associated with decreases in heart rate (p less than 0.05) and cardiac output (p less than 0.05). Ambulatory-determined 24-hour arterial pressure was unchanged after 6 months of exercise, but mean levels were slightly lower (4 mm Hg, p less than 0.05) after 12 months due to reductions in daytime (7 mm Hg, p less than 0.05) and nighttime (4 mm Hg, NS) systolic pressure; diastolic pressure was unchanged throughout the year of training. In the controls, conventionally recorded casual blood pressure levels were lower after 6 months (p less than 0.05), but no other changes were observed in any other variable over the 12 months of study. We conclude 1) regular low-intensity aerobic exercise at best produces only small reductions in 24-hour levels of arterial pressure in middle-aged and older humans with mild (diastolic) essential hypertension and 2) training-associated changes in casually determined blood pressure at rest are dependent on the measurement conditions and, most importantly, do not necessarily reflect the magnitude or even the direction of changes in arterial pressure throughout an entire day.
Risk factors for hypertension in a national cohort study.
Authors: Ford E S , Cooper R S
Published: June 2012

Hypertension continues to be a major public health problem in the United States. We used data from the National Health and Nutrition Examination Survey Epidemiologic Followup Study (1971-1984) to examine predictors of hypertension for the 7,073 participants free from hypertension at the baseline examination. The follow-up period averaged 10 years. Body mass index was positively related to the probability of hypertension developing among white men (n = 2,370), white women (n = 3,949), black men (n = 231), and black women (n = 523). Education was inversely associated with the probability of hypertension developing among white women and was of borderline significance among white men and black women. In a subanalysis of white men (n = 1,790) and white women (n = 3,063) who completed the 24-hour recall dietary questionnaire, dietary consumption of sodium, calcium, and potassium did not predict the development of hypertension. The failure of our study to support findings relating intake of dietary cations to the development of hypertension may be attributable to imprecision in the measurement of dietary data and misclassification of hypertension status. These data reinforce the importance of weight control in the primary prevention of hypertension.
Mechanical pressure versus intrinsic effects of hypertension on large arteries in humans.
Authors: Armentano R , Simon A , Levenson J , Chau N P , Megnien J L , Pichel R
Published: June 2012

Brachial artery diameter and compliance were measured in 23 normotensive control subjects and 49 hypertensive patients. The results were compared in isobaric conditions by a modeling analysis extrapolating from the measured data a short segment of the pressure-diameter and pressure-compliance curves in the artery. A logarithmic diameter-pressure function was used as well as measurements of brachial artery blood pressure and lumen diameter (by pulsed Doppler), and of brachial-to-radial pulse wave velocity (by mechanography). The measured values of diameter and compliance in the hypertensive patients were 109% and 63%, respectively, of the control group values. By extrapolating the data via the model at the same pressure level in all subjects (the average level of mean blood pressure of the two groups), the isobaric values of diameter and compliance in the hypertensive patients were 107% and 81%, respectively, of the control group values. Overall, measured isobaric diameters and measured compliance correlated with systolic, diastolic, and mean blood pressure values (p less than 0.001), whereas isobaric compliance correlated only with systolic (p less than 0.05) and pulse (p less than 0.01) pressure values. Thus, the increased diameter and reduced compliance of the brachial artery observed in hypertensive humans cannot be attributed solely to the stretching effect of elevated blood pressure, but also to intrinsic alteration of the arterial walls. These could represent either adaptative structural or functional changes secondary to the chronic increase in arterial pressure, or primary abnormalities of the vessel wall.
Peripheral dopamine in pathophysiology of hypertension. Interaction with aging and lifestyle.
Authors: Kuchel O G , Kuchel G A
Published: June 2012

Dopamine, an ancestral catecholamine, is physiologically natriuretic and vasodilating, thus essentially protecting against hypertension. Its actions are overshadowed by the opposite effects of its main biological partner, norepinephrine, and this is accentuated with aging. Clinical observations combined with molecular biology approaches to catecholamine-synthesizing and catecholamine-metabolizing enzymes and receptors permit the identification of some inborn defects. Subtle changes in the dopamine-norepinephrine balance may account for the enhanced peripheral noradrenergic activity seen in the setting of decreased dopaminergic activity in advanced age. These changes may contribute to the diminished ability of the aged kidney to excrete a salt load, as well as to the finding that systolic blood pressure increases with age in populations with a high, but not in those with a low, intake of salt. The attainment of advanced age in Western societies with adverse lifestyle changes (mental rather than physical stress, excess salt intake, overeating, sedentarism) appears to facilitate the development of hypertension. The adaptation to all the preceding lifestyle changes necessitates an increased dopamine generation, which may initially compensate to maintain appropriate natriuresis and vasodilation since many patients with initial borderline essential hypertension express their sympathetic hyperfunction, in addition to increased norepinephrine release, by excessive dopamine release. However, the progression of hypertension is accompanied by a peripheral dopaminergic deficiency and diminished ability to excrete salt. This may represent an eventual inadequacy of a phylogenetically redundant system resulting in decreased natriuresis and vasodilation and may account for the responsiveness of established chronic hypertension to salt restriction, diuretics, and dopaminomimetic medication.
Nerve growth factor synthesis in vascular smooth muscle.
Authors: Creedon D , Tuttle J B
Published: June 2012

Details of the interdependent, trophic relation between smooth muscle and its neural innervation are not well known despite suggestions that neural influences may contribute significantly to hypertensive and other cardiovascular disease. Vascular smooth muscle is a major target of innervation by neurons of the sympathetic nervous system. Sympathetic neurons depend on a constant supply of the potent neurotrophic peptide nerve growth factor. Nerve growth factor regulates an impressive list of neuronal and perhaps muscle properties, yet its source in vessels and the determinants of its synthesis are not known. We have taken advantage of the cytoarchitecture of the aorta to demonstrate that vascular smooth muscle cells synthesize nerve growth factor. The survival of cultured sympathetic neurons is supported in a nerve growth factor-dependent manner by co-culture with pure rat aortic vascular smooth muscle cells. Furthermore, pure smooth muscle cell cultures contain nerve growth factor-specific messenger RNA. Levels of messenger nucleic acid coding for nerve growth factor in smooth muscle are regulated by contractile agonists (angiotensin II, arginine vasopressin) and the adrenergic agonist phenylephrine. This suggests a link between muscle activity and growth factor production. Secretion of nerve growth factor protein by vascular smooth muscle was measured using a sensitive two-site immunoassay. Secretion is highest during muscle growth. Secretion is elevated by angiotensin II and arginine vasopressin but slightly inhibited by phenylephrine. These results suggest that cultured vascular smooth muscle can serve as a useful model in which to study the cellular regulation of trophic factor synthesis in health and disease.
Sodium excretion and racial differences in ambulatory blood pressure patterns.
Authors: Harshfield G A , Alpert B S , Pulliam D A , Willey E S , Somes G W , Stapelton F B
Published: June 2012

The influence of Na+ excretion and race on casual blood pressure and ambulatory blood pressure patterns was examined in a biracial sample of healthy, normotensive children and adolescents (10-18 years; n = 140). The slopes relating 24-hour urinary Na+ excretion to systolic blood pressure were different for both black and white subjects for casual blood pressure (p less than 0.001) and blood pressure during sleep (p less than 0.03). For casual blood pressure, the slope was significant for black subjects (beta = 0.17; p less than 0.001) but not for white subjects. For blood pressure during sleep, the slope was again significant for black subjects (beta = 0.08; p less than 0.01) but not for white subjects. Na+ excretion was also related to awake levels of systolic blood pressure for black subjects (beta = 0.08, r = 0.36; p less than 0.01), although the slopes for both black and white subjects were not significantly different. Further analyses indicated the results were not due to racial differences in 24-hour urinary K+ excretion. However, plasma renin activity was marginally related to Na+ excretion in white subjects (r = 0.22; p less than 0.06) but not black subjects, a finding that is consistent with previous studies. Na+ excretion was not associated with diastolic blood pressure or heart rate in either group under any condition. The results of this study support research that has demonstrated a stronger relation between Na+ handling and casual blood pressure in black subjects and extend these findings to blood pressure while the subject is both awake and asleep.
Arterial baroreceptor reflex function in borderline hypertensive rats.
Authors: DiBona G F , Jones S Y
Published: June 2012

With increased dietary NaCl intake (8% NaCl), the borderline hypertensive rat develops hypertension, thus expressing the phenotype of the spontaneously hypertensive parent. Since arterial baroreceptor reflex function is impaired in the spontaneously hypertensive parent, it was the objective of this study to examine arterial baroreceptor reflex function in the borderline hypertensive rat made hypertensive by increased dietary NaCl intake. Borderline hypertensive rats were fed either 1% or 8% NaCl from age 4 to 16 weeks. Borderline hypertensive rats fed 8% NaCl (n = 10) were hypertensive compared with borderline hypertensive rats fed 1% NaCl (n = 11) (141 +/- 3 versus 120 +/- 4 mm Hg, p less than 0.01). They were chronically instrumented for the recording of arterial pressure, heart rate, and renal sympathetic nerve activity. The percent change from control in heart rate and renal sympathetic nerve activity resulting from increases (phenylephrine) and decreases (nitroglycerine) in arterial pressure were measured in conscious freely moving animals. With respect to arterial baroreceptor reflex control of heart rate, 8% NaCl borderline hypertensive rats had a similar range (75 +/- 4%) and maximal gain (-2.72 +/- 0.24%/mm Hg) as 1% NaCl borderline hypertensive rats (70 +/- 4%; -2.78 +/- 0.50%/mm Hg). With respect to arterial baroreceptor reflex control of renal sympathetic nerve activity, 8% NaCl borderline hypertensive rats had values for range (205 +/- 22%) and maximal gain (-3.92 +/- 0.93%/mm Hg) that were not significantly different from those for 1% NaCl borderline hypertensive rats (167 +/- 33%, -2.76 +/- 0.62%/mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)
Effectiveness of advice to reduce alcohol consumption in hypertensive patients.
Authors: Maheswaran R , Beevers M , Beevers D G
Published: June 2012

The relation between alcohol consumption and blood pressure is well recognized, and advice to reduce alcohol plays an important part in the management of hypertensive patients. We have evaluated the effectiveness of this advice in a randomized, controlled, single-blind clinical study. After a 2-week run-in period, hypertensive men regularly consuming more than 20 units/wk (1 unit = 10 g) of alcohol were randomly assigned either to the "advice" or control group and were seen at 2-week intervals over an 8-week study period. The outcome measures were: reported alcohol consumption (1-week retrospective diary), markers of alcohol consumption (serum gamma-glutamyl transpeptidase, aspartate aminotransferase, uric acid, mean corpuscular volume), and blood pressure (sitting and standing). Over 18 months, 67 men who drank more than 20 units/wk of alcohol were seen. Twenty-six either were excluded, refused to participate, or dropped out due to nonattendance. Forty-one patients completed the study. After intervention, reported alcohol consumption fell from 60 units/wk to around 30 units/wk in the advice group, whereas it remained between 50 and 60 units/wk in the control group (analysis of variance [ANOVA] F = 7.1, p less than 0.05). This was accompanied by falls in gamma-glutamyl transpeptidase (20.9%) and aspartate aminotransferase (18.1%), but no significant changes were seen in the control group. Standing diastolic blood pressure fell significantly in the advice group (from 101.5 mm Hg to 96.3 mm Hg) compared with the control group (ANOVA F = 4.8, p less than 0.05). The results suggest that advice to reduce alcohol consumption is a useful form of treatment for hypertensive patients who drink excessively.
Enhanced myogenic responsiveness of renal interlobular arteries in spontaneously hypertensive rats.
Authors: Hayashi K , Epstein M , Loutzenhiser R
Published: June 2012

We recently demonstrated that the interlobular artery (ILA) constricts in response to elevating renal arterial pressure (RAP), suggesting that the ILA contributes to renal autoregulation. In the present study, we examined the segmental myogenic responsiveness of the ILA in kidneys from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The tapered nature of the ILA allowed us to characterize the regional responsiveness, using the basal diameter to define segments as either proximal (greater than 60 microns), intermediate (40-60 microns), or distal (less than 40 microns). At 80 mm Hg, segmental diameters were similar in WKY and SHR arteries (proximal, 76.0 +/- 3.1 versus 71.6 +/- 3.5 microns; intermediate, 48.2 +/- 1.4 versus 48.1 +/- 1.7 microns; distal, 30.7 +/- 0.9 versus 27.9 +/- 1.3 microns for WKY and SHR, respectively). In both strains, intermediate and distal segments exhibited graded reductions in diameter as RAP was elevated, whereas proximal segments did not. Pressure-induced decrements in the diameters of distal ILA segments were similar in WKY (-24 +/- 2%) and SHR (-20 +/- 2%; p greater than 0.1). The intermediate ILA of SHR exhibited an augmented myogenic responsiveness, constricting at lower RAP levels and exhibiting greater maximal decrements in diameter at 180 mm Hg (i.e., -19 +/- 2% and -12 +/- 2% for SHR and WKY, respectively; p less than 0.05). Nifedipine (1.0 microM) reduced pressure-induced vasoconstriction of intermediate and distal ILA segments by 56 +/- 11% and 79 +/- 7%, respectively, in WKY.(ABSTRACT TRUNCATED AT 250 WORDS)
Phorbol ester and atrial natriuretic peptide receptor response on vascular smooth muscle.
Authors: Yasunari K , Kohno M , Murakawa K , Yokokawa K , Horio T , Takeda T
Published: June 2012

At least two types of receptors for natriuretic peptides have been reported: biologically active receptors coupled with guanylate cyclase (atrial natriuretic peptide [ANP]-B receptors) and clearance receptors (ANP-C receptors). To elucidate the role of protein kinase C (PKC) in the regulation of ANP-B receptors, vascular smooth muscle cells in culture were treated with phorbol ester. Incubation with receptor agonists and phorbol ester led to the desensitization of receptor-mediated cyclic guanosine monophosphate (ANP-B receptor response) in rat vascular smooth muscle cells. Although a PKC inhibitor and downregulation of PKC by long-term incubation of cells with phorbol esters blocked the phorbol ester-induced desensitization of the ANP-B receptor response, they did not block the ANP-induced desensitization of the ANP-B receptor response. In addition, when desensitization by phorbol esters was observed, ANP was still capable of desensitization. These observations suggest that the mechanism for regulating ANP-B receptor sensitivity may be both PKC-dependent and PKC-independent and mediated by phorbol esters and ANP, respectively.
Correlation with blood pressure of the acetylcholine-induced endothelium-derived contracting factor in the rat aorta.
Authors: Iwama Y , Kato T , Muramatsu M , Asano H , Shimizu K , Toki Y , Miyazaki Y , Okumura K , Hashimoto H , Ito T
Published: June 2012

To examine a relation between the production of acetylcholine-induced endothelium-derived contracting factor and an increase in blood pressure, endothelium-dependent contraction and relaxation were evaluated by measuring the isometric tension of aortic rings from spontaneously hypertensive rats and Wistar-Kyoto rats at 5, 10, 20, and 30 weeks of age. In norepinephrine-precontracted rings, acetylcholine (10(-8) to 10(-5) M)-induced relaxations diminished at the doses of 10(-6) to 10(-5) M in both strains except at 5 weeks of age. Treatment with a thromboxane A2/prostaglandin H2 antagonist (ONO-3708) prevented this reduction in acetylcholine-induced relaxations in both strains and induced dose-dependent relaxations, which were completely inhibited by treatment with a nitric oxide inhibitor, NG-nitro-L-arginine methyl ester. In aorta treated with NG-nitro-L-arginine methyl ester without precontraction, acetylcholine induced dose-dependent contractions, which were greater in spontaneously hypertensive rats than in Wistar-Kyoto rats. These acetylcholine-induced contractions, which were observed only in rings with endothelium, were completely inhibited by treatment with ONO-3708 but not with a thromboxane A2 synthetase inhibitor (OKY-046). There was a statistically significant correlation between the acetylcholine-induced contractions and blood pressure. Release of 6-ketoprostaglandin F1 alpha by acetylcholine from the aorta was greater in spontaneously hypertensive rats. In vivo administration of another thromboxane A2/prostaglandin H2 antagonist (ONO-8809) (10 or 30 micrograms per body per day) for 3 weeks (5-8 weeks of age) did not affect blood pressure in either rat strain.(ABSTRACT TRUNCATED AT 250 WORDS)
Insulin resistance versus insulin secretion in the hypertension of obesity.
Authors: Istfan N W , Plaisted C S , Bistrian B R , Blackburn G L
Published: June 2012

We measured the degree of association between obesity, blood pressure, insulin resistance, and insulin secretion in 72 male and female obese hypertensive, obese nonhypertensive, and normal weight control subjects. Baseline weight, body mass index, percent body fat, waist/hip ratio, and systolic and diastolic blood pressures were obtained. Insulin sensitivity was assessed according to Bergman's minimal model. Twelve-hour urinary c-peptide was measured after a standard liquid meal. Insulin action was inversely associated with blood pressure status, obesity status, and age. Meal-stimulated c-peptide excretion significantly correlated with systolic blood pressure and percent fat but not with body mass index or age. Multivariate regression analysis indicated that, of the measures of body composition, percent fat and waist/hip ratio had the strongest correlation with insulin action either alone or in combination with c-peptide excretion. Obese hypertensive patients had an index of insulin action (10(-4).min-1/[microunits/ml]) of 1.34 +/- 0.19, which was significantly (p less than 0.003) lower than in the obese nonhypertensive patients (index, 2.26 +/- 0.10) or the nonobese subjects (index, 5.41 +/- 0.26, p less than 0.001). Meal-stimulated c-peptide excretion (nmol/kg lean body mass) was increased only in the obese hypertensive group (0.32 +/- 0.01) and was significantly higher (p less than 0.001) than in the obese nonhypertensive (0.16 +/- 0.01) or the nonobese subjects (0.14 +/- 0.01). These results support the hypothesis that abnormalities in blood pressure regulation, insulin-stimulated glucose uptake, and insulin secretion coexist.
Genetic divergence between the Wistar-Kyoto rat and the spontaneously hypertensive rat.
Authors: Johnson M L , Ely D L , Turner M E
Published: June 2012

A method of restriction fragment length polymorphism (RFLP) analysis was used to estimate the amount of genetic divergence between the spontaneously hypertensive rat (SHR) strain and the Wistar-Kyoto (WKY) strain. DNA from each strain was digested with eight restriction endonucleases and hybridized with six single copy gene sequences. The number of hybridization bands in each digestion was used to estimate the total number of bases analyzed and RFLPs were scored as single mutations. Divergence was then estimated by dividing the number of mutations by the number of bases analyzed. In a total of 808 bases analyzed in WKY rats, a minimum of 13 mutations were scored in SHR, which yields a nucleotide divergence of 1 change per 62 bp. This is an extremely high amount of divergence given the known origin of these two strains and is comparable to the maximum divergence possible between unrelated humans.
Endothelium-dependent relaxation and L-arginine metabolism in genetic hypertension.
Authors: Lee L , Webb R C
Published: June 2012

This study characterizes the effects of L-arginine and NG-monomethyl L-arginine on dilator responsiveness of vascular tissue from Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats. Rings of abdominal aorta were suspended in tissue baths for measurement of isometric force. After contraction induced by phenylephrine, cumulative addition of acetylcholine, L-arginine, or A23187 to the muscle bath caused a similar relaxation of aortic rings in both animal groups. To test the hypothesis that arginine metabolism is altered in hypertension, aortic rings were incubated with NG-monomethyl L-arginine. NG-monomethyl L-arginine (10-300 microM) did not affect contractile responses to phenylephrine (10(-10) to 10(-4) M) in either animal group (EC50, 10(-7) M). Exposure of aortic rings to NG-monomethyl L-arginine resulted in a greater inhibition of relaxation response to acetylcholine (10(-10) to 10(-6) M) in hypertensive animals. NG-monomethyl L-arginine (300 microM) caused complete inhibition of relaxation to acetylcholine in the hypertension group. Incubation with L-arginine (10-100 microM) overcame the inhibition of acetylcholine-induced relaxation produced by NG-monomethyl L-arginine in both groups. Exposure of aortic ring segments to NG-monomethyl L-arginine attenuated relaxation responses to A23187 (10(-10) to 3 x 10(-6) M) in both groups. L-Arginine-induced reversal of the inhibitory effect of NG-monomethyl L-arginine on the relaxation responses to A23187 was similar between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Relation between job strain, alcohol, and ambulatory blood pressure.
Authors: Schnall P L , Schwartz J E , Landsbergis P A , Warren K , Pickering T G
Published: June 2012

"Job strain" (defined as high psychological demands and low decision latitude on the job) has been previously reported to be associated with increased risk of hypertension and increased left ventricular mass index (LVMI) in a case-control study of healthy employed men, aged 30-60 years, without evidence of coronary heart disease. We hypothesized that job strain would be associated with increased ambulatory blood pressure (AmBP). A total of 264 men at eight work sites wore an AmBP monitor for 24 hours on a working day. In an analysis of covariance model, job strain was associated with an increase in systolic AmBP of 6.8 mm Hg (p = 0.002) and diastolic AmBP of 2.8 mm Hg at work (p = 0.03) after adjusting for age, race, body mass index, Type A behavior, alcohol behavior, smoking, work site, 24-hour urine sodium, education, and physical demand level of the job. Alcohol use also had a significant effect on AmBP. However, among subjects not in high-strain jobs, alcohol had no apparent effect on AmBP at work. Instead, alcohol use and job strain interacted such that workers in high-strain jobs who drank regularly had significantly higher systolic AmBP at work (p = 0.007). Among the other risk factors, only age, body mass index, and smoking had significant effects on AmBP. Job strain also had significant effects on AmBP at home and during sleep as well as on LVMI.(ABSTRACT TRUNCATED AT 250 WORDS)
Relation of central hemodynamics to obesity and body fat distribution.
Authors: Jern S , Bergbrant A , Björntorp P , Hansson L
Published: June 2012

Central obesity increases the risk for cardiovascular disease, but little is known about its hemodynamic effects. The aims were to investigate the influence of obesity (as defined by body mass index) and abdominal fat accumulation (as defined by the waist/hip ratio) on hemodynamics at rest and during mental stress. Invasive hemodynamic studies were performed in 20 healthy, normotensive young men (aged 18-22 years) recruited from an unbiased population sample. Their body mass index and waist/hip ratio ranged between 18.5 and 30.2 (mean 24.1) and 0.77 and 0.98 (mean 0.87), respectively. Hemodynamics were related to the two anthropometric indexes by bivariate regression analyses. Cardiac output and stroke volume were positively correlated to body mass index (p = 0.05 and p = 0.005), but inversely to waist/hip ratio (p = 0.01 and p = 0.01). Mental stress augmented the hemodynamic patterns. Total peripheral resistance during stress correlated inversely to body mass index (p = 0.02), whereas high waist/hip ratio was associated with higher systemic vascular resistance p = 0.002). The delta CO/delta MAP ratio, i.e., relative contribution of cardiac output for the stress-induced increase in mean arterial pressure, showed a strong positive association with body mass index (p = 0.004), but was inversely related to the waist/hip ratio (p = 0.002). Serum insulin correlated significantly to the stress-induced change in total peripheral resistance (r = 0.54; p = 0.02), whereas the increase in cardiac output was inversely related to insulin (r = -0.59; p = 0.007). Thus, central obesity is associated with a specific hemodynamic pattern characterized by higher total peripheral resistance, lower cardiac output, and a vasoconstrictor response to psychosocial stress.
Salt-dependency of endothelin-induced, chronic hypertension in conscious rats.
Authors: Mortensen L H , Fink G D
Published: June 2012

The effect of salt intake on the hypertensive response to long-term infusion of endothelin-1 was investigated. Chronically instrumented male Sprague-Dawley rats (325-375 g) were used in a 15-day protocol that included 3 control days followed by 7 days of endothelin-1 infusion at 5.0 pmol.kg-1.min-1 and 5 days of recovery. Rats were maintained on either a normal sodium chloride intake (2.0 meq Na+ per day; normal sodium) or a high sodium chloride intake (6.0 meq Na+ per day; high sodium) throughout the protocol. Control rats received normal or high sodium intakes but not endothelin-1. In high-sodium rats, endothelin-1 produced a significant increase in mean arterial pressure and total peripheral resistance; a significant bradycardia was observed only on the first day after the start of the endothelin-1 infusion. Cardiac output, stroke volume, water balance, and urinary sodium and potassium excretion remained unchanged. Termination of endothelin-1 infusion resulted in rapid normalization of both arterial pressure and peripheral resistance. In contrast, normal sodium rats exhibited no alteration in mean arterial pressure, heart rate, total peripheral resistance, stroke volume, water balance, or urinary sodium and potassium excretion throughout the endothelin-1 infusion protocol. The hypertension produced by endothelin-1 infusion cannot be explained by alterations in salt or water balance since endothelin-1 infusion in high sodium animals produced significant increases in mean arterial pressure with no observable changes in water or electrolyte balance. These results indicate that endothelin-induced hypertension in conscious rats is a salt-dependent model of hypertension.
Pressor responsiveness in corticosteroid-induced hypertension in humans.
Authors: Pirpiris M , Sudhir K , Yeung S , Jennings G , Whitworth J A
Published: June 2012

In previous studies short-term cortisol increased cold pressor responses and the rise in forearm vascular resistance accompanying intra-arterial norepinephrine without an increase in overall resting sympathetic nervous activity. The present study examined whether these alterations in pressor response are glucocorticoid or mineralocorticoid effects, or both. Normal male subjects (n = 12) received either fludrocortisone, 0.3 mg daily (n = 6), or dexamethasone, 3 mg daily (n = 6), for 7 days. Hemodynamic studies were performed before and on day 7 of treatment. Fludrocortisone increased body weight from 69.3 +/- 1.8 to 71.1 +/- 2 kg (p less than 0.001), cardiac output from 5.0 to 6.0 l/min (+/- 0.1, p less than 0.01), mean arterial pressure from 82 +/- 1 to 91 +/- 1 mm Hg (p less than 0.001), cold pressor responsiveness from 13.0 to 39.0 mm Hg/ml per 100 ml per minute (R units) (+/- 4.3, p less than 0.01), and forearm vascular response to intra-arterial norepinephrine (F = 59.4, p less than 0.01) and angiotensin II (F = 30.8, p less than 0.01) infusions. Total peripheral resistance fell from 22.0 to 20.1 mm Hg/l per minute (+/- 0.3, p less than 0.05). Dexamethasone did not increase cardiac output, 5.1 to 5.2 l/min (+/- 0.1), or body weight but did increase mean arterial pressure from 82 +/- 3 to 91 +/- 3 mm Hg (p less than 0.001), cold pressor responsiveness from 8.6 to 17.1 R units (+/- 2.8, p less than 0.05), and forearm vascular response to intra-arterial norepinephrine (F = 33.0, p less than 0.01) and angiotensin II (F = 54.9, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Plasma norepinephrine responses to head-up tilt are misleading in autonomic failure.
Authors: Meredith I T , Eisenhofer G , Lambert G W , Jennings G L , Thompson J , Esler M D
Published: June 2012

The failure of plasma norepinephrine to rise during upright posture is accepted as a diagnostic sign of autonomic nervous failure in patients with postural hypotension. Our clinical experience has been that this test is misleading, with an increase in plasma norepinephrine commonly occurring. To test whether this might result from absent reflex postural venous constriction lowering cardiac output and plasma norepinephrine clearance, we measured norepinephrine plasma kinetics during recumbency and 30 degrees head-up tilting in six patients with pure autonomic failure and eight healthy subjects. Mean arterial pressure fell by 54 +/- 8 mm Hg with head-up tilt in the patients with pure autonomic failure. The plasma norepinephrine concentration (arterial sampling) increased 73 +/- 29 pg/ml (mean difference +/- SED, p less than 0.02), solely because of a 36% reduction in the clearance of norepinephrine from plasma (0.78 +/- 0.09 l/min, p less than 0.0001). In normal subjects, plasma norepinephrine concentration rose by 112 +/- 20 pg/ml (p less than 0.001), largely because of a 24% increase in norepinephrine spillover to plasma (190 +/- 20 ng/min, p less than 0.005). When the postural fall in blood pressure and cardiac output in the pure autonomic failure patients was prevented by the selective venoconstrictor dihydroergotamine (10 micrograms/kg i.v.), no fall in plasma clearance or rise in plasma concentration of norepinephrine occurred. Measurement of the change in plasma norepinephrine with postural stimulation in patients with orthostatic hypotension is not a reliable diagnostic test for autonomic failure because elevations can occur in the plasma concentration that are entirely attributable to reduced plasma norepinephrine clearance.
Increased vascular angiotensin formation in female rats harboring the mouse Ren-2 gene.
Authors: Hilgers K F , Peters J , Veelken R , Sommer M , Rupprecht G , Ganten D , Luft F C , Mann J F
Published: June 2012

Rats harboring the mouse Ren-2 transgene develop hypertension despite low levels of plasma renin activity. We tested the hypothesis that these rats exhibit an increase in vascular angiotensin formation caused by the presence of the transgene. We measured the release of angiotensins I and II from isolated perfused hindquarters by high-performance liquid chromatography and radioimmunoassay. Female rats heterozygous for the transgene had significantly elevated mean arterial pressure compared with control rats (189.3 +/- 9.5 versus 110.0 +/- 5.4 mm Hg, p less than 0.05). Plasma angiotensin II was significantly decreased in transgenic rats. Transgenic rat hindquarters released more angiotensin I (121 +/- 37 versus 39 +/- 12 fmol/30 min, n = 7 each) and more angiotensin II (210 +/- 21 versus 62 +/- 12 fmol/30 min, p less than 0.05, n = 7 each) than control rat hindquarters. Captopril increased angiotensin I release and decreased angiotensin II values in both transgenic and control rat hindquarters. Bilateral nephrectomy 24 hours before hindquarter perfusion greatly reduced angiotensin release from control rat hindquarters but not from transgenic rat hind limbs. We also tested for the presence of Ren-2 messenger RNA in mesenteric and aortic tissue by RNase protection assay and Northern blot analysis. We found that Ren-2 messenger RNA was present in mesenteric and aortic tissue of transgenic but not of control rats. We conclude that the Ren-2 transgene is expressed in vascular tissue of transgenic rats and may be responsible for substantial increases in vascular angiotensin formation.