bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of cellular calcium in salt sensitivity of patients with essential hypertension.
Authors: Oshima T , Matsuura H , Matsumoto K , Kido K , Kajiyama G
Published: June 2012

The mechanism by which excessive sodium chloride intake raises blood pressure has not been fully clarified. The present study was therefore undertaken in patients with essential hypertension to investigate the possible role of an intracellular calcium-dependent mechanism in salt sensitivity. The difference in mean blood pressure between a week of low sodium chloride diet (3 g/day) and a week of high sodium chloride diet (20 g/day) was studied in relation to the intracellular free calcium concentration in lymphocytes and an acute hypotensive response to a 10-mg sublingual dose of nifedipine in 12 inpatients. Sodium chloride loading induced significant increases in mean blood pressure (from 111 +/- 12 to 122 +/- 11 mm Hg; p less than 0.01), intracellular free calcium in lymphocytes (from 133 +/- 13 to 145 +/- 9 nmol/L; p less than 0.01), and the hypotensive response to nifedipine (from 19 +/- 6 to 31 +/- 10 mm Hg; p less than 0.01). In addition, serum total calcium concentration was decreased while urinary calcium excretion was increased. The elevation of mean blood pressure was closely and positively correlated with the increase in intracellular free calcium concentration (r = 0.71, p less than 0.05) and the increase in the hypotensive effect of nifedipine (r = 0.91, p less than 0.01) after sodium chloride loading. However, changes in these values had no relation to the change in serum concentration or urinary excretion of calcium. These data suggest that change in the cellular calcium-dependent vasoconstriction mechanism may be associated with salt sensitivity of patients with essential hypertension.
Role of pressor prostanoids in rats with angiotensin II-salt-induced hypertension.
Authors: Mistry M , Nasjletti A
Published: June 2012

This study was designed to assess the contribution of thromboxane A2 to high blood pressure in rats with angiotensin II (Ang II)-salt hypertension. Hypertension was induced in rats drinking 0.15 M NaCl by infusion of Ang II (125 ng/min i.p.) for 12 days. Relative to values in water-drinking rats without Ang II infusion, Ang II-salt hypertensive rats exhibited augmentation (p less than 0.05) of blood pressure (from 129 +/- 3 to 217 +/- 12 mm Hg), urinary thromboxane B2 excretion (from 5.4 +/- 0.9 to 25.4 +/- 2.1 ng/day), and thromboxane B2 release from renal cortex slices (from 71.3 +/- 6.7 to 121.1 +/- 14.4 pg/mg) and aortic rings (from 28.8 +/- 2.9 to 115.8 +/- 12.8 pg/mg). Treatment with an inhibitor of thromboxane A2 synthetase, UK 38485, had no effect on blood pressure in normotensive and Ang II-salt hypertensive rats. Treatment with a thromboxane A2 receptor blocker, SQ 29548, decreased blood pressure in Ang II-salt hypertensive rats from 191 +/- 9 to 152 +/- 9 mm Hg after 3 hours, but it had no effect on blood pressure in normotensive rats. Since SQ 29548 interfered with the pressor effects of the prostaglandin endoperoxide analogue U-46619, prostaglandin F2 alpha, and 9 alpha,11 beta-prostaglandin F2, we suggest that the SQ 29548-induced blood pressure reduction in Ang II-salt hypertensive rats is the manifestation of blockade of the vascular actions of one or more endogenous prostanoids including thromboxane A2 and prostaglandin endoperoxides. If so, pressor prostanoids may be contributory factors in the pathogenesis of severe Ang II-salt hypertension in rats.
Altered circadian blood pressure rhythm in patients with Cushing's syndrome.
Authors: Imai Y , Abe K , Sasaki S , Minami N , Nihei M , Munakata M , Murakami O , Matsue K , Sekino H , Miura Y
Published: June 2012

The circadian blood pressure rhythm was compared in patients with Cushing's syndrome, essential hypertension, and primary aldosteronism. In patients with essential hypertension or primary aldosteronism, a clear nocturnal fall in systolic and diastolic blood pressure and heart rate was observed. This fall was seen in untreated subjects as well as in patients receiving combined treatment with a calcium antagonist, diuretic, converting enzyme inhibitor, alpha-blocker and beta-blocker, or sympatholytic drug. In these groups, there was a positive correlation between heart rate and systolic or diastolic blood pressure. On the other hand, in patients with Cushing's syndrome, there was no nocturnal fall in blood pressure but in some patients a rise was observed. In all patients there was a nocturnal fall in heart rate. Thus, there was no significant correlation between heart rate and blood pressure in these patients. Exogenous glucocorticoid eliminated the normal nocturnal fall of blood pressure in patients with chronic glomerulonephritis or systemic lupus erythematosus. These results suggest that the changed circadian blood pressure pattern in patients with Cushing's syndrome is not due to antihypertensive treatment or to the mineralocorticoid excess accompanying this disease, but it is attributable to excess glucocorticoid or the associated disturbance in the adrenocorticotropic hormone-glucocorticoid system (or both). This conclusion also implies that the normal circadian rhythm of blood pressure may be regulated at least in part by the adrenocorticotropic hormone-glucocorticoid system.
Pressure-diuresis in volume-expanded rats. Tubular reabsorption in superficial and deep nephrons.
Authors: Roman R J
Published: June 2012

Micropuncture experiments were performed in volume-expanded rats to better define the nephron segments in which changes in renal perfusion pressure inhibit tubular reabsorption. Neural influences on the kidney were eliminated by renal denervation, and plasma levels of vasopressin, aldosterone, corticosterone, and norepinephrine were maintained at fixed levels by i.v. infusion. Fractional excretion of sodium, chloride, and water increased markedly after renal perfusion pressure was elevated from 110 to 150 mm Hg. Renal blood flow, glomerular filtration rate, and single nephron glomerular filtration rate measured from deep and superficial nephrons were unsaltered. Reabsorption of chloride and water in the proximal tubule of superficial nephrons decreased by 10% after renal perfusion pressure was elevated and contributed to the pressure-diuretic response. Changes in renal perfusion pressure also altered the reabsorption of water and chloride in juxtamedullary nephrons. The percentage of the filtered water load reaching the tip of the loop of Henle increased from 19.8 +/- 2.9 to 38.1 +/- 3.0% after renal perfusion pressure was elevated. Chloride delivery rose from 34.2 +/- 4.3 to 65.2 +/- 4.8% of the filtered load. These results support the view that alterations in medullary hemodynamics participate in the pressure-natriuretic response by inhibiting tubular reabsorption in the proximal tubule or the thin descending limb of the loop of Henle (or both) of juxtamedullary nephrons.
Left ventricular mass and exercise responses predict future blood pressure. The Muscatine Study.
Authors: Mahoney L T , Schieken R M , Clarke W R , Lauer R M
Published: June 2012

Increased blood pressure and left ventricular mass are associated with increased morbidity and mortality in adults with coronary heart disease. To define the predictors of subsequent childhood blood pressure and left ventricular mass, serial echocardiograms and blood pressure responses during exercise were studied in 274 children aged 6 to 15 years, whose systolic blood pressures were in the high, middle, or low range. Persistence of rank order for left ventricular mass and blood pressure, at rest and during exercise, was maintained over a mean follow-up period of 3.4 years, with correlations ranging from 0.33 to 0.44. Subsequent systolic blood pressure was best predicted from initial resting and maximal exercise systolic blood pressures and left ventricular mass. Subsequent left ventricular mass was best predicted from initial left ventricular mass and maximal exercise diastolic blood pressure, but resting systolic blood pressure did not add to this latter prediction. Since left ventricular mass relates best to exercise blood pressure and not to resting blood pressure, left ventricular mass may provide an integrated view of the effects of blood pressure both at rest and during stress. We speculate that increased left ventricular mass in childhood may be an important predictor of subsequent hypertension and its consequences.
Cerebral circulation in chronic arterial hypertension.
Authors: Baumbach G L , Heistad D D
Published: June 2012

Several new concepts have emerged recently regarding the effects of chronic hypertension on cerebral blood vessels. First, hypertrophy of large cerebral arteries in chronic hypertension attenuates increases in pressure of downstream vessels and protects the cerebral microvasculature. Second, in contrast to large cerebral arteries, which become less distensible during chronic hypertension, distensibility of cerebral arterioles increases during chronic hypertension despite hypertrophy of the arteriolar wall. Third, dilatation of cerebral blood vessels with disruption of the blood-brain barrier, and not vasospasm, appears to be the critical factor in the pathogenesis of hypertensive encephalopathy. This concept is supported by the finding that cerebral edema in stroke-prone spontaneously hypertensive rats is preceded by vasodilatation and disruption of the barrier. Fourth, alterations of endothelium-mediated dilatation may impair vasodilator responses in chronic hypertension and predispose to ischemia. Finally, chronic hypertension impairs dilatation of collateral blood vessels in the cerebral circulation. The implication of this finding is that increased susceptibility to cerebral infarction in chronic hypertension may be related in part to compromised responses of the collateral circulation.
The discovery of nitric oxide as the endogenous nitrovasodilator.
Authors: Moncada S , Palmer R M , Higgs E A
Published: June 2012

Endothelium-derived relaxing factor (EDRF) is a labile humoral agent released by vascular endothelium that mediates the relaxation induced by some vasodilators, including acetylcholine and bradykinin. EDRF also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to vascular endothelium. These actions of EDRF are mediated through stimulation of the soluble guanylate cyclase and the consequent elevation of cyclic guanosine 3',5'-monophosphate. EDRF has been identified as nitric oxide (NO). The pharmacology of NO and EDRF is indistinguishable; furthermore, sufficient NO is released from endothelial cells to account for the biological activities of EDRF. Organic nitrates exert their vasodilator activity following conversion to NO in vascular smooth muscle cells. Thus, NO may be considered the endogenous nitrovasodilator. NO is synthesized by vascular endothelium from the terminal guanido nitrogen atom(s) of the amino acid L-arginine. This indicates the existence of an enzymic pathway in which L-arginine is the endogenous precursor for the synthesis of NO. The discovery of the release of NO by vascular endothelial cells, the biosynthetic pathway leading to its generation, and its interaction with other vasoactive substances opens up new avenues for research into the physiology and pathophysiology of the vessel wall.
Effect of chronic hypertension on acute hypertensive disruption of the blood-brain barrier in rats.
Authors: Werber A H , Fitch-Burke M C
Published: June 2012

The effect of chronic hypertension on acute hypertensive disruption of the blood-brain barrier has been studied in only two models of hypertension, with inconsistent results. The purpose of this study was to reinvestigate whether chronic hypertension has a consistent effect on acute hypertensive disruption of the blood-brain barrier and to determine whether one of the previously studied models has an unusual response to chronic hypertension. We studied four rat models of chronic hypertension: spontaneously hypertensive rats (SHR), two-kidney, 1 clip Goldblatt rats (2K1C), rats treated with deoxycorticosterone acetate (DOCA) and NaCl, Dahl salt-sensitive rats fed a high salt diet, and two groups of normotensive controls: Wistar-Kyoto rats (WKY) and Dahl salt-sensitive rats fed a low salt diet. We caused acute hypertension in some rats with the use of bicuculline (1.2 mg/kg) and aortic occlusion. Rats without acute hypertension served as controls. Blood-brain barrier disruption was quantitated using the brain/blood ratio of 125I-labeled albumin. Acute hypertensive disruption was less in SHR, rats treated with DOCA-NaCl, and Dahl salt-sensitive rats fed a high salt diet, but not in 2K1C rats, as compared with normotensive controls. Acute hypertensive disruption was greater in Dahl salt-sensitive rats fed a low salt diet than in WKY. A series of control WKY, SHR, rats treated with DOCA-NaCl, 2K1C rats, and Dahl salt-sensitive rats fed low or high salt diets, but not subjected to acute hypertension, were also studied. Brain/blood 125I-albumin ratios were significantly less in these control rats not subjected to acute hypertension than in rats subjected to acute hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Propranolol increases prostacyclin synthesis in patients with essential hypertension.
Authors: Beckmann M L , Gerber J G , Byyny R L , LoVerde M , Nies A S
Published: June 2012

We tested the hypothesis that vascular prostacyclin synthesis is increased by propranolol and could account for some of the drug's antihypertensive effect. We studied 10 white patients with mild essential hypertension in a randomized, double-blind design to assess the effects of indomethacin with or without the addition of propranolol on blood pressure and vascular prostacyclin biosynthesis, as assessed by the urinary excretion of the major enzymatically produced metabolite of prostacyclin, 2,3-dinor-6-keto-prostaglandin F1 alpha (PGF1 alpha), F1 alpha (PGF1 alpha), measured by gas chromatography-mass spectrometry. Seven patients responded to propranolol with a lowering of mean arterial blood pressure in both supine and upright postures. The fall in mean arterial blood pressure (-14.1 +/- 2.1 mm Hg sitting; -17.4 +/- 1.7 mm Hg supine) with propranolol alone was significantly greater than that produced when propranolol was given to patients receiving indomethacin (-7.8 +/- 1.9 mm Hg sitting; -7.7 +/- 3.0 mm Hg supine). Our drug-responsive patients demonstrated a significantly lower excretion rate of 2,3-dinor-6-keto-PGF1 alpha than was found in an age and sex-matched group of normal volunteers. With propranolol treatment, drug-responsive patients showed a significant increase in the excretion of 2,3-dinor-6-keto-PGF1 alpha, such that the mean excretion was not significantly different from that in normal volunteers. Indomethacin caused a significant rise in mean arterial blood pressure and a significant fall in 2,3-dinor-6-keto-PGF1 alpha excretion, and it blocked the rise in urinary 2,3-dinor-6-keto-PGF1 alpha associated with propranolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in autonomic regulation induced by physical training in mild hypertension.
Authors: Pagani M , Somers V , Furlan R , Dell'Orto S , Conway J , Baselli G , Cerutti S , Sleight P , Malliani A
Published: June 2012

The adaptive effects of physical training on cardiovascular control mechanisms were studied in 11 subjects with mild hypertension. In these subjects we assessed the gain of the heart period-systolic arterial pressure relationship in the unfit and the fit state by using 1) an open loop approach, whereby the gain is expressed by the slope of the regression of heart period as a function of systolic arterial pressure, during a phenylephrine-induced pressure rise and 2) a closed loop approach with proper simplification, whereby the gain is expressed by the index alpha, obtained through simultaneous spectral analysis of the spontaneous variabilities of heart period and systolic arterial pressure. Both methods indicated that training significantly increased the gain of the relationship between heart period and systolic arterial pressure at rest and reduced arterial pressure and increased heart period significantly. This gain was drastically reduced during bicycle exercise both in the unfit and fit state. In a second group of normotensive (n = 7; systolic pressure, 133 +/- 3 mm Hg) and hypertensive (n = 7; systolic pressure, 180 +/- 10 mm Hg) subjects undergoing 24-hour diagnostic continuous electrocardiographic and high fidelity arterial pressure monitoring, the index alpha was significantly reduced in the hypertensive group at rest. Furthermore, when analyzed continuously over the entire 24-hour period, this index underwent minute-to-minute changes with lower values during the day and higher values during the night. We propose the index alpha as a quantitative indicator of the changes in the gain of baroreceptor mechanisms occurring with physical training in mild hypertension and during a 24-hour period in ambulatory subjects.
Increased membrane-bound calcium in platelets of hypertensive patients.
Authors: Cooper R , Lipowski J , Ford E , Shamsi N , Feinberg H , Le Breton G
Published: June 2012

The fluorescent indicator chlortetracycline was used to estimate membrane-bound calcium in mild, untreated hypertensive patients (n = 39) and normotensive controls (n = 42). All participants were black. After incubation with chlortetracycline, platelet-rich plasma was centrifuged into a pellet and fluorescence was measured with a microspectrofluorometer. At an interval of 45 minutes mean fluorescence values were 11% higher in the hypertensive than in the normotensive group (567 +/- 95 vs. 512 +/- 100 counts/sec, p less than 0.02). With both groups of participants combined, a correlation of borderline statistical significance was noted between diastolic blood pressure and chlortetracycline fluorescence (r = 0.213, p = 0.056). In parallel experiments, sodium and potassium concentrations were measured in red blood cells. Intracellular sodium was also significantly higher in the hypertensive group (p less than 0.01). These data indicate that the total cell burden of calcium is increased in the platelets of hypertensive individuals, possibly a result of abnormal cell metabolism of calcium, and further suggest that circulating platelets in hypertensive individuals may be in a hyperaggregable state.
Red-cell sodium-lithium countertransport and fractional excretion of lithium in normal and hypertensive humans.
Authors: Weinberger M H , Smith J B , Fineberg N S , Luft F C
Published: June 2012

To examine the relations between erythrocyte sodium-lithium countertransport and renal proximal tubular sodium handling, we measured countertransport, and then subjected 30 normal and 32 hypertensive subjects, both white and black, to provocative maneuvers of volume expansion and contraction. The fractional excretions of sodium and lithium were measured simultaneously. In agreement with previous studies, we found that countertransport in erythrocytes was elevated in hypertensive patients compared with normal subjects. We also observed that whites have a higher level of countertransport than blacks. In the basal state, we found that fractional sodium excretion of hypertensive patients was no different than in normal subjects, whereas the fractional lithium excretion of hypertensive persons was increased compared with normotensive values. Volume expansion with 2 1 0.9% saline administered intravenously during a 4-hour period provoked an exaggerated natriuresis and a greater increase in fractional lithium clearance in hypertensive patients compared with the control group. With volume expansion and contraction, fractional lithium clearance and countertransport were directly correlated. Our data suggest that hypertensive persons do not have increased proximal tubular sodium reabsorption compared with normal subjects. Further, the exaggerated natriuresis of hypertension is, in part, the result of increased distal solute delivery. The fact that our hypertensive patients were older may partially explain the discrepancies between this report and previous observations.
Distribution of sodium-lithium countertransport and blood pressure in Caucasians five to eighty-nine years of age.
Authors: Turner S T , Weidman W H , Michels V V , Reed T J , Ormson C L , Fuller T , Sing C F
Published: June 2012

Case-control studies suggest that increased erythrocyte sodium-lithium countertransport may predict increased susceptibility to the development of essential hypertension. To characterize interindividual variation in sodium-lithium countertransport and its relation to blood pressure levels in the general population, we studied 1,475 Caucasians between 5 and 89 years of age (711 males and 764 females) ascertained through 266 households with children in the schools of Rochester, Minnesota. Individuals who were taking antihypertensive agents or combinations of estrogen and progesterone were not included in the sample. A third-order polynomial regression on age accounted for only a small fraction of variability in sodium-lithium countertransport (2.8% in males, p less than 0.001; 2.1% in females, p less than 0.01), whereas a fourth-order regression on age accounted for a large proportion of variability in systolic blood pressure (45.7% in males, p less than 0.001; 52.5% in females, p less than 0.001) and diastolic blood pressure (39.8% in males, p less than 0.001; 33.0% in females, p less than 0.001). Mean sodium-lithium countertransport was higher in males than females at all ages; but the rank order of male and female means for systolic and diastolic blood pressure was age dependent. Positively skewed distributions for age-, height-, and weight-adjusted sodium-lithium countertransport in male and female cohorts between 5-19.9, 20-49.9, and 50-89.9 years of age were explained significantly better by postulating a mixture of two partially overlapping sodium-lithium countertransport distributions rather than a single normal distribution (p less than 0.01). Among men in the 20-49.9-year-old cohort, adjusted sodium-lithium countertransport values in the upper distribution were associated with higher systolic and diastolic blood pressure (mean +/- SD) than values in the lower distribution (for systolic blood pressure: 115 +/- 11 vs. 111 +/- 11 mm Hg, p less than 0.07; for diastolic blood pressure: 71.2 +/- 8.0 vs. 68.4 +/- 8.6 mm Hg, p less than 0.08). Among females in the 50-89.9-year-old cohort, adjusted sodium-lithium countertransport values in the upper distribution were associated with significantly greater diastolic blood pressure than values in the lower distribution (77 +/- 10 vs. 70 +/- 9 mm Hg, p less than 0.03).(ABSTRACT TRUNCATED AT 400 WORDS)
Neurogenic pressor episodes fail to cause hypertension, but do induce cardiac hypertrophy.
Authors: Julius S , Li Y , Brant D , Krause L , Buda A J
Published: June 2012

Repeated neurogenic pressor episodes by hindquarter compression were elicited in nine experimental dogs. Conscious dogs underwent 6 hours of compression every day over a period of 9 weeks. The average mean blood pressure increase during the compression periods was 25 mm Hg, but after decompression the blood pressure promptly returned to baseline values. This blood pressure response was constant and did not change over the 9-week period. The blood pressure increase was associated with a significant increase of plasma norepinephrine values. After validity of the model was established, echocardiographic measurements were performed at baseline and after 3, 6, and 9 weeks of compression in six experimental and six time-control dogs. Concentric left ventricular hypertrophy was already detectable at 3 weeks, and at the ninth week, the left ventricular mass was 28% above the baseline value. The left ventricular mass in time-control dogs remained unchanged over the same period of time. The time-left ventricular mass curves in experimental dogs were significantly different (by profile analysis), had different means (p less than 0.005), were not parallel (p less than 0.0006), and the overall group difference was highly significant (p less than 0.00001). Since left ventricular hypertrophy, a poor prognostic sign in clinical situations, can evolve before established hypertension, present therapeutic recommendations based on permanently elevated blood pressure values may not be entirely justified.
Angiotensin II induces c-fos expression in smooth muscle via transcriptional control.
Authors: Naftilan A J , Pratt R E , Eldridge C S , Lin H L , Dzau V J
Published: June 2012

Angiotensin II (Ang II) has been shown to cause hypertrophy of cultured quiescent rat aortic smooth muscle cells. This observation along with the recent demonstration of angiotensinogen messenger RNA (mRNA) in the vessel wall has led us to postulate a role for Ang II in hypertensive smooth muscle hypertrophy. One of the earliest responses in a wide variety of cells in response to a growth-promoting agent is the induction of the proto-oncogene c-fos. To investigate the mechanism of the action of Ang II, we investigated the effect of Ang II on the expression of the c-fos gene in rat aortic smooth muscle cells that were made quiescent by being grown in a defined serum-free media for 48 hours. Ang II (10(-6)-10(-10) M) resulted in a dose-dependent increase in c-fos mRNA expression. This induction was angiotensin-receptor specific since it was completely abolished by the competitive inhibitor saralasin. Inhibition of protein synthesis did not block the rise in c-fos mRNA expression; it resulted in a superinduction and stabilization of the c-fos mRNA. Using a nuclear runoff transcription assay, we demonstrated that Ang II stimulated the transcription rate of the c-fos gene. This activation of c-fos gene expression may be an important mechanism in the angiotensin-induced smooth muscle hypertrophy.
Cardiovascular effects of the N-methyl-D-aspartate receptor antagonist MK-801 in conscious rats.
Authors: Lewis S J , Barres C , Jacob H J , Ohta H , Brody M J
Published: June 2012

Evidence from microinjection studies in anesthetized rats suggests that central excitatory amino acid pathways using N-methyl-D-aspartate receptors are involved in the regulation of the cardiovascular system. To test the hypothesis that these pathways are tonically involved in the maintenance of or the baroreceptor reflex regulation of cardiovascular function, we have examined the effects of intravenous injection of the centrally acting, noncompetitive N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), on the mean arterial pressure, heart rate, renal sympathetic nerve activity, and behavior of conscious, freely moving sham-operated and sinoaortic baroreceptor-denervated rats. Administration of MK-801 produced, within 5 minutes, dose-dependent elevations in mean arterial pressure, heart rate, and renal sympathetic nerve activity that were sustained for 0.5 to 2.5 hours. For an equivalent dose, MK-801 produced approximately twice the peak changes in mean arterial pressure and heart rate in the sinoaortic baroreceptor-denervated rats than in the sham-operated rats. Pretreatment results were as follows: 1) The ganglion blocker chlorisondamine markedly attenuated the hypertension and tachycardia in the sham-operated and sinoaortic baroreceptor-denervated rats, 2) pretreatment with the alpha 1-adrenergic receptor antagonist prazosin virtually abolished the hypertension, and 3) the beta 1-adrenergic receptor antagonist atenolol markedly reduced the tachycardia. MK-801 also produced stereotypic behaviors and ataxia in the sham-operated and sinoaortic baroreceptor-denervated rats; however, qualitatively and quantitatively similar changes in behavior were induced in the latter by doses approximately five time lower than required in sham operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of cytosolic free Ca2+ concentration in vascular smooth muscle cells by A- and C-kinases.
Authors: Sharma R V , Bhalla R C
Published: June 2012

The cytosolic free Ca2+ concentration [( Ca2+]i) was measured in cultured human umbilical vein smooth muscle cells using fura-2 as a Ca2+ indicator and microscopic digital image analysis system. Activation of cells with histamine and vasopressin resulted in a prompt though transient rise in [Ca2+]i 10- to 12-fold higher than the resting [Ca2+]i. The [Ca2+]i then declined rapidly during the first 30-40 seconds after hormonal stimulation and then gradually decreased to near resting levels in 2-3 minutes in the continued presence of hormones. The magnitude of the increase in peak [Ca2+]i was similar in buffered salt solution containing 1.8 mM Ca2+, zero Ca2+, and zero Ca2+ buffered salt solution containing 10 mM La3+, suggesting that receptor-mediated increase in [Ca2+]i is primarily due to the release of Ca2+ from the intracellular stores. Addition of La3+ produced oscillations in [Ca2+]i in approximately half the cells in response to both hormones. Addition of 10 microM forskolin did not significantly affect the resting [Ca2+]i, the hormone-stimulated peak [Ca2+]i, or the time course of hormone-stimulated [Ca2+]i transients. These data suggest that mechanisms involved in A-kinase-mediated smooth muscle relaxation may be subsequent to the changes in [Ca2+]i. Activation of C-kinase by 1 microM 12 deoxyphorbol 13-isobutyrate-20 acetate (DPBA) did not affect the resting [Ca2+]i, though it attenuated the histamine and vasopressin-mediated peak elevation in [Ca2+]i. Since DPBA inhibited the peak [Ca2+]i response to both the hormones to the same extent, it would appear that C-kinase activation may uncouple the receptor-mediated activation of phospholipase C.
Urinary sodium pump inhibitor raises cytosolic free calcium concentration in rat aorta.
Authors: Goto A , Yamada K , Ishii M , Yoshioka M , Ishiguro T , Eguchi C , Sugimoto T
Published: June 2012

We were able to purify two distinct sodium pump inhibitors to homogeneity from human urine based on [3H]ouabain-displacing activity from intact human erythrocytes. The polar and less polar compounds were eluted off the C18 reverse-phase column with 18% and 31% acetonitrile, respectively. The polar compound cross-reacted very weakly with specific antidigoxin antibody and lacked a characteristic ultraviolet absorption peak between 190 and 300 nm. The less polar compound showed a prominent digoxinlike immunoreactivity and had an ultraviolet spectrum similar to that of digoxin. We examined the effects of these compounds on cytosolic free calcium concentration in cultured rat vascular smooth muscle cells (A10 cells) using the fluorescent calcium chelator fura-2. Only the polar ouabain-displacing compound caused a significant increase, from 108 +/- 7 to 162 +/- 8 nM (n = 6, p less than 0.01), in cytosolic free calcium concentration in A10 cells. The rise in cytosolic free calcium concentration induced by the polar ouabain-displacing compound tended to be slower in onset and more sustained than that induced by arginine vasopressin. In contrast, ouabain and bufalin had no appreciable effects on cytosolic free calcium concentration in A10 cells. These results suggest that the polar ouabain-displacing compound we isolated from human urine may possess a vasoactive property and may play an important role in the modulation of vascular tone.
Pathogenesis of weight-related changes in blood pressure in dogs.
Authors: Rocchini A P , Moorehead C P , DeRemer S , Bondie D
Published: June 2012

We have previously shown that weight gain in the dog results in an increase in blood pressure. To study the pathogenesis of the rise in blood pressure associated with weight gain, we compared the serial changes in blood pressure, body weight, sodium balance, plasma volume, and three hormones known to affect sodium balance (norepinephrine, insulin, and aldosterone) in seven dogs fed a high fat diet for 6 weeks and seven dogs fed a control diet. The sodium content of both diets was equal. During a 2-week control period, no differences were noted between the two groups. Weight gain was associated with a progressive increase in blood pressure (mean pressure increased by 18.5 +/- 2.1 mm Hg in the high fat group) and plasma volume (plasma volume increased from 1,426 +/- 202 to 2,053 +/- 250 ml in the high fat group). Sodium retention occurred after 1 week of the high fat diet and persisted. Over the 6-week period, the dogs on the high fat diet increased their cumulative sodium balance by 2,024 +/- 462 meq versus an increase of only 289 +/- 97 meq for the dogs on the control diet. In the high fat diet group of dogs, there was a significant relation between change in cumulative sodium balance and the change in blood pressure and plasma volume. After 1 week of the high fat diet, norepinephrine was the only hormone that significantly increased from baseline. Over the next 5 weeks norepinephrine increased no further, whereas fasting insulin and aldosterone progressively increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of kinin in regulation of rat submandibular gland blood flow.
Authors: Berg T , Carretero O A , Scicli A G , Tilley B , Stewart J M
Published: June 2012

In tissues rich in kallikrein, vasodilator kinins, acting as paracrine hormones, may play a role in the local regulation of blood flow. We studied the role of kinins in the regulation of blood flow in the rat submandibular gland using a kinin analogue with antagonistic properties, [DArg0]Hyp3-Thi5-8[DPhe7]bradykinin. When infused into the carotid artery (20 micrograms/min/rat), this antagonist blocked the effect of bradykinin (25-250 ng/kg, intracarotid injection) on glandular blood flow. In nephrectomized rats, the antagonist also blocked the increase in glandular blood flow caused by enalaprilat, a kininase II converting enzyme inhibitor. At a dose of 20 micrograms/min/rat, the antagonist produced no detectable change in basal glandular blood flow; however, at a higher dose (100 micrograms/min/rat), it caused a significant decrease (p less than 0.001). In eight of 10 rats, blood flow decreased by 75% or more; this effect was not blocked by the alpha-adrenergic receptor antagonist phentolamine. After antagonist infusion was stopped, blood flow returned toward normal. Sympathetic nerve stimulation of the gland induced vasoconstriction followed by poststimulatory vasodilatation. In rats displaying severe vasoconstriction after the antagonist, postsympathetic vasodilatation was abolished even when stimulation was performed after the antagonist infusion had been stopped and blood flow returned toward normal. Although a direct vasoconstrictor effect of the kinin antagonist cannot be completely ruled out, these data suggest that, in the rat submandibular gland, kinins may play a role in regulation of basal blood flow and vasodilatation after converting enzyme inhibitor or sympathetic stimulation.
Ethnic differences in blood pressure, pulse rate, and related characteristics in young adults. The CARDIA study.
Authors: Liu K , Ballew C , Jacobs D R , Sidney S , Savage P J , Dyer A , Hughes G , Blanton M M
Published: June 2012

This study examined ethnic differences in blood pressure and pulse rate in young adults to see whether the differences, if they exist, can be explained by differences in body mass index, lifestyle, psychological, and socioeconomic characteristics. Data used were from the baseline examination of the Coronary Artery Risk Development in (Young) Adults Study (CARDIA). CARDIA is a longitudinal study of lifestyle and evolution of cardiovascular disease risk factors in 5,116 young adults, black and white, men and women, aged 18-30 years, of varying socioeconomic status. Young black adults had higher mean systolic blood pressure and slightly higher mean diastolic blood pressure than young white adults. For both men and women, the blood pressure differences between blacks and whites tended to be greater for the age group 25-30 than for the age group 18-24 years. Among the variables studied, body mass index, duration of exercise on the treadmill, number of cigarettes smoked per day, and number of alcoholic drinks per week were consistently associated with blood pressure. The blood pressure differences were greatly reduced after adjusting for these variables. Black participants had lower mean pulse rate than white participants. The differences tended to be greater for the age group 18-24 than for the age group 25-30 years. Among the variables studied, only duration on treadmill and number of cigarettes smoked per day were consistently correlated with pulse rate. With adjustment for duration on treadmill, the differences in pulse rate increased. These results suggest that differences in ethnic pattern of blood pressures and pulse rate with age may be due in part to obesity, physical fitness, alcohol consumption, and cigarette smoking.
Role of angiotensin converting enzyme and other peptidases in in vivo metabolism of kinins.
Authors: Ishida H , Scicli A G , Carretero O A
Published: June 2012

Arterial plasma kinins and mean arterial pressure were measured in intact and bilaterally nephrectomized rats infused with vehicle or bradykinin to study the role of 1) angiotensin converting enzyme (ACE) and other peptidases and 2) the kidney (a kininase-rich organ) in the metabolism of kinins in vivo. Before the infusion, rats were pretreated with vehicle, enalaprilat (an ACE inhibitor), or a cocktail of kininase inhibitors containing 1) enalaprilat, 2) DL-2-mercaptomethyl-3-guanidinoethyl-thiopropanoic acid (MGTA), a carboxypeptidase N inhibitor, 3) phosphoramidon, a neutral endopeptidase 24.11 inhibitor, and 4) bestatin, an aminopeptidase B inhibitor. In the rats with vehicle (n = 8), the cocktail did not significantly increase endogenous kinins (from 31 +/- 6 to 41 +/- 9 pg/ml, p = 0.94). In the rats infused with bradykinin (peptidase substrate), plasma kinins increased threefold in the group pretreated with the vehicle, 21-fold in the enalaprilat group, and 22-fold in the cocktail group. These increases were doubled by nephrectomy but were not affected by ureteral ligation. In the groups pretreated with the cocktail or enalaprilat, the hypotensive effect of bradykinin was correlated with plasma kinin concentration (r = 0.75, p less than 0.001). After bradykinin infusion was stopped, plasma kinins decreased by half in 10-12 seconds in the rats pretreated with vehicle, enalaprilat, or cocktail. We concluded that ACE and the kidney are important to the metabolism of circulating kinins while carboxypeptidase N, neutral endopeptidase 24.11 and aminopeptidase B are not. We also concluded that other tissue peptidases, not affected by either the above inhibitors or nephrectomy, play an important role in kinin metabolism.
Arginine vasopressin-induced hypertrophy of cultured rat aortic smooth muscle cells.
Authors: Geisterfer A A , Owens G K
Published: June 2012

Recently we reported that the contractile agonist angiotensin II induces hypertrophy, not hyperplasia, in cultured rat aortic smooth muscle cells (Geisterfer AAT, Peach MJ, Owens GK: Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res 1988;62:749-756). We have further explored the hypothesis that contractile agonists are important regulators of smooth muscle cell growth by examining the effects of another contractile agonist, arginine vasopressin, on growth of cultured rat aortic smooth muscle cells. Autoradiographic analysis as well as cell number determinations showed that arginine vasopressin (1 microM) did not stimulate proliferation in cells made quiescent in a defined serum-free media nor did it augment proliferation in 0.4% fetal bovine serum. However, flow cytometric analysis of cellular protein content demonstrated that arginine vasopressin (1 microM) did induce cellular hypertrophy in quiescent cultures after 4 days of treatment, increasing smooth muscle cell protein content by 35% as compared with vehicle-treated controls. The increase in protein content showed a concentration dependence. Cellular hypertrophy was accompanied by an increase in [35S]methionine incorporation, which was elevated 45% by 24 hours. Both the increase in [35S]methionine incorporation and the increase in protein content could be prevented by the specific arginine vasopressin receptor antagonist. [1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine] arginine vasopressin. An increase in [35S]methionine incorporation was observed between 12 and 24 hours after treatment of quiescent smooth muscle cells for only 5 minutes with arginine vasopressin (1 microM). Arginine vasopressin-induced increases in [35S]methionine incorporation was increased within 6 hours after treatment. These studies show that arginine vasopressin, like angiotensin II, induces hypertrophy but not hyperplasia of cultured rat aortic smooth muscle cells.
Effect of decaffeinated versus regular coffee on blood pressure. A 12-week, double-blind trial.
Authors: van Dusseldorp M , Smits P , Thien T , Katan M B
Published: June 2012

The effect of decaffeinated versus regular coffee on blood pressure and heart rate was investigated. In a randomized double-blind, crossover trial, 45 healthy volunteers (23 women and 22 men, 25-45 years old) with a habitual intake of 4-6 cups coffee/day received 5 cups of regular coffee each day for a period of 6 weeks, and 5 cups of decaffeinated coffee for the next 6 weeks or vice versa. The background diet was kept constant. The total amount of caffeine ingested was 40 mg during the decaffeinated coffee period and 445 mg during the regular coffee period. Use of decaffeinated coffee led to a significant but small decrease in systolic (mean +/- SEM, -1.5 +/- 0.4 mm Hg; p = 0.002) and diastolic (-1.0 +/- 0.4 mm Hg; p = 0.017) ambulant blood pressure and to a small increase in ambulant heart rate (+1.3 +/- 0.6 beats/min; p = 0.031). Individual differences in rate of caffeine metabolism did not explain differences in long-term response of blood pressure to caffeine. We conclude that in normotensive adults replacement of regular by decaffeinated coffee leads to a real but small fall in blood pressure. However, it remains to be established whether a mass switch from regular to decaffeinated coffee would significantly reduce the total incidence of hypertension-related disorders.
INTERSALT study findings. Public health and medical care implications.
Authors: Stamler J , Rose G , Stamler R , Elliott P , Dyer A , Marmot M
Published: June 2012

INTERSALT found a significant association between 24-hour urine sodium excretion and systolic blood pressure in individuals. There was also a significant association between sodium and slope (increase) of blood pressure with age across population samples. The weight of evidence from animal-experimental, clinical, intervention, and epidemiological data favors a causal relation. INTERSALT data from 52 centers in 32 countries permit an estimate of effect on average population blood pressure of lower sodium intake. Based on the sodium-blood pressure association in individuals, it was estimated that a habitual population sodium intake that was lower by 100 mmol/day (e.g., 70 vs. 170 mmol/day) would correspond to an average population systolic pressure that was lower by at least 2.2 mm Hg. This size difference in systolic blood pressure in major US and UK population studies is associated with 4% lower risk of coronary death and 6% lower risk of stroke death in middle age. If habitual diet is both lower in sodium and higher in potassium with lower alcohol intake and less obesity, INTERSALT data estimate average population systolic pressure would be lower by 5 mm Hg. This was calculated to correspond to a 9% lower risk of coronary death and a 14% lower risk of stroke death. INTERSALT cross-population data also suggest that, with a 100 mmol/day lower sodium intake over the life span, the average increase in population systolic pressure from age 25 to 55 years would be less by 9 mm Hg, corresponding at age 55 to a 16% lower risk of subsequent coronary death and 23% lower risk of stroke death.(ABSTRACT TRUNCATED AT 250 WORDS)
Perivascular innervation of the mesenteric artery in spontaneously hypertensive rats.
Authors: Kawamura K , Ando K , Takebayashi S
Published: June 2012

Perivascular innervation of the mesenteric arteries of 7-week-old and 6-month-old spontaneously hypertensive rats and normotensive Wistar-Kyoto rats was examined. The densities of neuropeptide Y-containing nerve fibers and adrenergic nerve fibers were increased in the distal regions of mesenteric arteries of spontaneously hypertensive rats as compared with findings in Wistar-Kyoto rats. However, the densities of cholinergic nerve fibers, vasoactive intestinal polypeptide-containing, and substance P-containing nerve fibers in the mesenteric arteries of the spontaneously hypertensive rats were unchanged in comparison with findings in the Wistar-Kyoto rats. Thus, not only adrenergic nerve fibers but also neuropeptide Y-containing nerve fibers may play an important role in the development and maintenance of hypertension in spontaneously hypertensive rats.
Atrial natriuretic factor modulates proximal glomerulotubular balance in anesthetized rats.
Authors: Zhuo J L , Harris P J , Skinner S L
Published: June 2012

The extent to which the natriuretic effect of a prolonged low dose infusion of atrial natriuretic factor (30 ng/kg/min) is dependent on interference with the prevailing intrarenal actions of angiotensin II was examined before and after blockade of angiotensin production with the converting enzyme inhibitor enalaprilat (5 mg/kg). Lithium clearance was used to assess proximal tubular sodium and water reabsorption. Atrial natriuretic factor and enalaprilat caused similar increases in sodium excretion (10-fold and sevenfold, respectively) and glomerular filtration rate (each 34%) and similar decreases in fractional proximal reabsorption of sodium (17% and 13%, respectively) and blood pressure. Each also caused a major disruption in the effectiveness of proximal glomerulotubular balance (30% and 50% of perfect balance). Infusion of atrial natriuretic factor during converting enzyme inhibition increased glomerular filtration rate further by 23%, reaching 63% above control without change in renal blood flow but with a rise in filtration fraction to 0.48. Sodium excretion increased further but fractional proximal sodium reabsorption remained constant and proximal glomerulotubular balance appeared to improve. Atrial natriuretic factor therefore possesses a glomerular action that persists during converting enzyme inhibition and is indeed additive to the removal of angiotensin II when the proximal effect of atrial natriuretic factor is no longer apparent. It is concluded that failure of atrial natriuretic factor to further suppress fractional proximal sodium reabsorption during converting enzyme inhibition is caused by either prior removal of the stimulatory action of angiotensin II on proximal tubular transport or extreme changes in peritubular physical factors consequent on the high filtration fraction.