bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal nerves and the development of Dahl salt-sensitive hypertension.
Authors: Osborn J L , Roman R J , Ewens J D
Published: June 2012

Several experimental forms of hypertension require intact renal innervation for the development or maintenance (or both) of the elevated arterial pressure. We determined the relationships between urinary sodium and water excretion and arterial pressure in Dahl salt-sensitive rats (DS) with innervated (n = 6) and denervated (n = 7) kidneys after switching from a low to a high sodium diet. Arterial pressure significantly increased in both groups within 48 hours after they began to eat an 8% sodium chloride diet. This hypertension increased to 188 +/- 9 and 190 +/- 7 mm Hg, respectively, in rats with innervated and denervated kidneys after 12 days. Mean arterial pressures were not significantly different between groups on any day. The rise in arterial pressure of DS placed on a high sodium intake was associated with an elevation of urine flow rate and urinary sodium excretions in rats with either innervated or denervated kidneys. Urine flow rates and urinary sodium excretions were greater in denervated than in innervated rats on Days 4 through 7 after beginning the high sodium diet. This diuresis and natriuresis in rats with denervated kidneys were associated with greater water and sodium intakes on Days 4 to 7 of the high sodium diet when compared with rats with innervated kidneys. These results demonstrate that, following exposure to a high sodium intake, DS have increased arterial pressure within 24 hours. The development of this arterial hypertension is not dependent on intact renal innervation. In conscious DS, the renal innervation does participate in the regulation of urinary sodium excretion by promoting renal sodium and water reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)
Dynamic cardiovascular responses to infusions of atrial natriuretic factor in humans.
Authors: Ebert T J , Skelton M M , Cowley A W
Published: June 2012

We sought to demonstrate a hypotensive effect from infusions of atrial natriuretic factor (ANF) into humans and to describe the mechanism(s) of this effect. Cardiovascular and hormonal responses to human ANF-(99-126) (125 ng/kg bolus followed by a 30-minute infusion at 25 ng/kg/min) were determined in eight conscious volunteers and compared with responses of eight time-control subjects who received isotonic saline. Baseline levels of ANF (52.8 +/- 5.5 pg/ml) increased 8.8-fold after 30 minutes of ANF infusion but were unchanged in the time controls. Plasma levels of renin, aldosterone, vasopressin, sodium, potassium, and osmolality did not change during infusions. A transient 5% reduction in mean arterial pressure related to a 12% reduction in peripheral resistance was observed 10 minutes after the priming bolus of ANF. This response was not sustained during the remainder of the ANF infusion period, nor did it occur in two additional subjects who received ANF infusions without the priming bolus. Steady state responses consisted of significant reductions in central venous pressure (15%), stroke volume (13%), and cardiac output (10%), but no reduction in blood pressure. Plasma norepinephrine levels and peripheral resistance increased (34% and 9%, respectively) during ANF administration. These data indicate that steady state responses to ANF in humans consist of decreases in cardiac filling pressures, which reduce cardiac output, unload cardiopulmonary baroreceptors, and activate the sympathetic nervous system. Blood pressure is well maintained despite striking increases in plasma ANF.
Characterization of recombinant human prorenin and renin.
Authors: Carilli C T , Vigne J L , Wallace L C , Smith L M , Wong M A , Lewicki J A , Baxter J D
Published: June 2012

A cell line that secretes substantial quantities of recombinant human prorenin was prepared by transfecting Chinese hamster ovary cells with a gene encoding preprorenin. The prorenin was purified to homogeneity and was found to have a single amino terminus, reflecting cleavage after a typical 23 amino acid signal sequence. The purified inactive prorenin was not a substrate for active renin and was not capable of self-activation. Prorenin could be converted to renin by addition of exogenous protease, and deglycosylation of the prorenin did not alter the sensitivity to protease activation. The enzymatic activity of deglycosylated renin was kinetically identical to that of the native protein. Multimilligram quantities of recombinant human renin and prorenin were purified, providing suitable material for studies directed toward greater understanding of the function of these proteins and for structural studies such as x-ray diffraction for use in design of renin inhibitors.
Suppression of angiotensin II release by prostaglandin synthesis inhibitors in hind legs.
Authors: Mizuno K , Higashimori K , Inagami T
Published: June 2012

Previously we reported that immunoreactive angiotensin II (Ang II) release from isolated perfused rat mesenteric arteries was mediated by beta-adrenergic receptor activation. However, the precise mechanism of regulation of vascular renin-angiotensin is not completely understood. In this study, we examined the effect of indomethacin and meclofenamate on immunoreactive angiotensin I (Ang I) and immunoreactive Ang II release from perfused rat hind leg vasculature to delineate the possible relevance of prostaglandins to the vascular renin-angiotensin system in vitro. We also examined the effects of isoproterenol and propranolol on the immunoreactive Ang I and II release. Isolated rat hind legs were perfused with Krebs-Ringer solution, and immunoreactive Ang I and II released into the perfusate were measured directly by using a Sep-Pak C18 cartridge connected to the perfusion system. Indomethacin and meclofenamate (10(-8) to 2 X 10(-6) M) added to the perfusion medium suppressed immunoreactive Ang I and II release to similar extents in a dose-dependent manner (p less than 0.001); the maximal percent inhibition of immunoreactive Ang II release evoked by these inhibitors (2 X 10(-6) M) was 60 +/- 6% (p less than 0.001) for indomethacin and 50 +/- 4% (p less than 0.001) for meclofenamate. Isoproterenol (10(-6) M) failed to cause a change in the release of both peptides, but propranolol (10(-6) M) slightly decreased the release of immunoreactive Ang I and II by 28 +/- 4% (p less than 0.001) and 32 +/- 4% (p less than 0.001), respectively. There was a highly significant positive correlation between the released amount of immunoreactive Ang I and that of immunoreactive Ang II altered by indomethacin (r = 0.91), meclofenamate (r = 0.94), or propranolol administration (r = 0.90). These results suggest that the renin-angiotensin in the hind legs is modulated by prostaglandins and that a difference exists in the beta-adrenergic receptor-mediated release of Ang II among diverse vascular beds.
Endogenous digitalislike circulating substances in spontaneously hypertensive rats.
Authors: Wauquier I , Pernollet M G , Grichois M L , Lacour B , Meyer P , Devynck M A
Published: June 2012

Circulating digitalislike compounds have been proposed to be involved in some Na+-dependent types of experimental hypertension and in human essential hypertension. The level of circulating Na+-K+ pump inhibitor(s) was investigated in the spontaneously hypertensive rat of the Okamoto strain (SHR), its normotensive control, Wistar-Kyoto rat (WKY), and the regular Wistar rat using the following criteria: the ability of whole plasma to inhibit the total active Na+ efflux from Wistar rat erythrocytes and to cross-react with digoxin antibodies and the ability of plasma extracts to inhibit Na+,K+-adenosine triphosphatase (ATPase) activity of membranes from rat kidney. SHR plasma inhibited the net Na+ efflux from Wistar erythrocytes by up to 27% compared with WKY or Wistar plasma. For a given number of cells, the inhibition increased with the amount of available plasma. Cross-reactivity with digoxin antibodies was twice as high in SHR as in WKY or Wistar plasma. It was already enhanced in 3- to 4-week-old rats. Plasma extracts from SHR significantly inhibited Na+,K+-ATPase activity when compared with WKY extracts (75.6 +/- 2.6 vs 89.3 +/- 2.4 mumol Pi/mg/hr; p less than 0.01) but did not differ from Wistar plasma extracts. These results strongly suggest that circulating digitalislike compound(s) are present in elevated amounts in SHR as early as 3 to 4 weeks of age, but their exact participation in blood pressure elevation or maintenance remains to be clarified.
Attenuation of fructose-induced hypertension in rats by exercise training.
Authors: Reaven G M , Ho H , Hoffman B B
Published: June 2012

This study was initiated to see if the insulin resistance, hyperinsulinemia, and hypertension that follow feeding normotensive Sprague-Dawley rats a fructose-rich diet could be prevented by letting rats run spontaneously in exercise wheel cages. Blood pressure in sedentary rats increased from (mean +/- SEM) 125 +/- 2 to 148 +/- 3 mm Hg in response to 2 weeks of a high fructose diet, and this increment was significantly (p less than 0.001) attenuated in exercising rats (from 121 +/- 1 to 131 +/- 2 mm Hg). In addition, mean (+/- SEM) plasma insulin concentration was lower in fructose-fed rats allowed to run spontaneously (44 +/- 2 vs 62 +/- 5 microU/ml; p less than 0.01). Finally, resistance to insulin-stimulated glucose uptake was assessed by determining the steady state plasma glucose response to a continuous glucose and exogenous insulin infusion during a period in which endogenous insulin secretion was suppressed. The results of these studies indicated that the mean (+/- SEM) steady state plasma glucose concentration was significantly lower in the exercise-trained rats (127 +/- 5 vs 168 +/- 6 mg/dl; p less than 0.001), despite the fact that the steady state plasma insulin levels were also lower in rats allowed to run spontaneously (75 +/- 4 vs 90 +/- 5 microU/ml; p less than 0.05). Thus, the ability of exercise-trained rats to stimulate glucose disposal was enhanced as compared with that of sedentary rats fed the same fructose-rich diet. These data demonstrate that the insulin resistance, hyperinsulinemia, and hypertension produced in normotensive rats by feeding them a high fructose diet can be attenuated if rats are allowed to run spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)
Sensitivity of caudal arteries and the mesenteric vascular bed to norepinephrine in DOCA-salt hypertension.
Authors: Longhurst P A , Rice P J , Taylor D A , Fleming W W
Published: June 2012

This study was undertaken to determine what factors might contribute to arterial supersensitivity to norepinephrine associated with deoxycorticosterone acetate (DOCA)-salt hypertension in the rat. Experimental groups of male rats were uninephrectomized and 1 week later began receiving twice weekly injections of DOCA (20 mg/kg s.c. in sesame oil) plus 1% NaCl and 0.2% KCl in their drinking water. For each experimental group, a group of age-matched male rats underwent a sham operation and received injections of sesame oil and the NaCl-KCl drinking water. Perfused caudal arteries from 3-week-hypertensive rats were supersensitive to intraluminal and extraluminal norepinephrine administration. However, this difference in sensitivity between hypertensive and control caudal arteries was demonstrable at low rates of perfusion, 0.5 to 1.0 ml/min, but not at rates of 2.0 to 2.6 ml/min. The supersensitivity was not due to differences in neuronal uptake or to inhibition of extraneuronal uptake by DOCA. The perfused mesenteric vascular bed from 3- or 6-week-hypertensive rats was also supersensitive to intraluminal norepinephrine. However, the demonstration of supersensitivity in the mesenteric vasculature was independent of perfusion rate (2.3-6.8 ml/min) and perfusion pressure in the range of 30 to 60 mm Hg. There was little or no supersensitivity to transmural nerve stimulation in either the caudal artery or the mesenteric vasculature, a finding consistent with the observed decrease in endogenous norepinephrine content. Microelectrodes were used to determine resting membrane potential in the smooth muscle cells. No differences in resting membrane potential were detected between caudal or mesenteric arteries from hypertensive compared with control rats 2, 3, or 6 weeks after initiation of the DOCA-salt regimen. It is concluded that 1) the perfusion rate is a critical factor in designing experiments to test the sensitivity of caudal arteries to drugs, 2) the perfused mesenteric vascular bed is a useful preparation for studying sensitivity of blood vessels in hypertension, 3) the supersensitivity of blood vessels in the DOCA-salt model may be of greater importance relative to circulating catecholamines than to sympathetic innervation, and 4) the supersensitivity of blood vessels to norepinephrine in the DOCA-salt model is not due to changes in neuronal uptake, extraneuronal uptake, or membrane potential of the vascular smooth muscle cells.
Significance of renal vasodilation after administration of atrial natriuretic factor in the conscious dog.
Authors: Hintze T H
Published: June 2012

The contribution of alterations in renal hemodynamics to the diuretic and natriuretic actions of atrial natriuretic factor (ANF) was studied in chronically instrumented conscious dogs. Injection of ANF-(99-119), 10 micrograms/kg, had no effect on mean arterial pressure, heart rate, renal blood flow, or calculated renal vascular resistance; However, it increased urine flow rate (86 +/- 20%) and sodium (118 +/- 24%) and potassium (35 +/- 22%) excretion (p less than 0.05). In contrast, ANF-(99-122), 10 micrograms/kg, significantly increased renal blood flow (26 +/- 4.5%), reduced renal vascular resistance (24 +/- 2.9%) and arterial pressure (5.5 +/- 1.9%), and markedly increased urine flow rate (198 +/- 34%) and sodium (206 +/- 32%) and potassium (75 +/- 27%) excretion (p less than 0.05), being almost twice as effective in the first 10 minutes as was ANF-(99-119) infusion. During a brief infusion, ANF-(99-122) (10 micrograms/kg/min for 4 minutes) increased renal blood flow (24 +/- 2.7%), heart rate (18 +/- 5.7%), urine flow rate (199 +/- 25%), and sodium (290 +/- 81%) and potassium (104 +/- 17%) excretion. Injection of radioactive microspheres (15 or 9 micron) to measure intrarenal distribution of blood flow during the steady state increase in renal blood flow indicated that ANF-(99-122) infusion preferentially increased outer cortical blood flow. Blood flow in the four zones of the kidney cortex (Zone 1, outer, and Zone 4, inner) increased 96 +/- 25% (Zone 1), 199 +/- 87% (Zone 2), 139 +/- 47% (Zone 3), p less than 0.05, and 25 +/- 28% (Zone 4, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiogenic hypertension in maturing dogs.
Authors: Magrini F , Roberts N , Branzi G , Mondadori C , Reggiani P , Ciulla M , Meazza R
Published: June 2012

The purpose of this study was to evaluate whether the heart can induce high blood pressure by maintaining an inappropriately elevated cardiac output/body weight ratio during growth. Direct (femoral artery) mean arterial pressure (MAP), heart rate, cardiac output/body weight ratio (as defined by M-mode echocardiography), and total peripheral vascular resistance were measured and calculated every 2 months in nine conscious dogs during development from 2 to 10 months of age. In four dogs a J-shaped catheter for atrial pacing was chronically implanted at the age of 3 months, and their hearts were permanently paced at 130 beats/min until maturity. The aim of atrial pacing was to prevent the natural slowing of the heart rate and, consequently, to maintain a cardiac output/body weight ratio that was inappropriately high in relation to age during growth. Five dogs were studied as controls. No hemodynamic differences were observed until the age of 4 months. From the age of 5 to 10 months heart rate was kept at 130 beats/min by atrial pacing in the atrially paced group, and the mean cardiac output/body weight ratio did not decrease (196 +/- 24 vs 191 +/- 34 [SE] ml/min/kg). MAP rose from 62 +/- 4 to 116 +/- 8 mm Hg, and total peripheral resistance increased from 0.34 +/- 0.07 to to 0.61 +/- 0.09 mm Hg/ml/min/kg.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcium transport and vitamin D in three breeds of spontaneously hypertensive rats.
Authors: Schedl H P , Wilson H D , Horst R L
Published: June 2012

Conflicting results have been published by different laboratories comparing the rate of intestinal calcium transport and concentration of circulating 1,25-dihydroxyvitamin D (1,25-[OH]2D) in the spontaneously hypertensive rat (SHR) and control Wistar-Kyoto rat (WKY): They have been reported to be greater, the same, or lower in the SHR than in the WKY. We tested the possibility that the conflicting results might be breeder-related by measuring 1) the rate of intestinal mucosal calcium transport, 2) the concentration of circulating 25-hydroxyvitamin D (25-OH-D) and 1,25-(OH)2D, and 3) the concentration of intestinal mucosal receptor for 1,25-(OH)2D in the two strains of animals from three different breeders. Sodium and water transport were also measured because of their relevance to hypertension. Blood pressure was always higher and calcium, as well as mean sodium and water transport, was always lower in the SHR than in the WKY. The concentration of 1,25-(OH)2D was the same, higher, or lower in the SHR than in the WKY and was age- and breeder-dependent. Mean mucosal 1,25-(OH)2D receptor concentration was higher in the SHR and was variable, depending on breeder. We conclude that 1) the rate of calcium transport is lower in the SHR than in the WKY and independent of breeder and concentration of 1,25-(OH)2D in serum, 2) the variability in 1,25-(OH)2D concentration among investigators may be breeder-dependent, and 3) the higher receptor concentration in the intestinal mucosa of the SHR could be a compensatory response to the decreased rate of calcium transport. These differences in calcium and sodium transport may be an expression in the enterocyte of factors etiological for hypertension.
Glucocorticoid modulation of beta-adrenergic receptors of cultured rat arterial smooth muscle cells.
Authors: Jazayeri A , Meyer W J
Published: June 2012

Since both glucocorticoids and catecholamines are involved in the regulation of normal blood pressure, we investigated the modulation of beta-adrenergic receptors of cultured rat arterial smooth muscle cells by glucocorticoids. The synthetic glucocorticoids dexamethasone and RU 28362, at 10(-8) M concentration, increased maximum beta-adrenergic binding but had no effect on the dissociation constant (Kd). Each steroid caused an increase in maximum [3H]dihydroalprenolol binding over the concentration range of 10(-8) to 10(-6) M, but not at 10(-9) M. The glucocorticoid effect on beta-adrenergic receptors of arterial smooth muscle cells required a minimum of 20 hours of incubation in the presence of the steroid and was significantly inhibited by cycloheximide (10 micrograms/ml), indicating that the glucocorticoid effect required protein synthesis. The effect of dexamethasone on [3H]dihydroalprenolol binding was significantly inhibited by the glucocorticoid antagonist RU 38486. Basal and agonist-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) levels in arterial smooth muscle cells, before and after glucocorticoid treatment, were measured as an indicator of the physiological significance of the observed glucocorticoid-induced increase in beta-adrenergic receptor binding. While causing no change in the basal cAMP level, treatment of arterial smooth muscle cells with 10(-6) M dexamethasone for 24 hours increased the 10(-6) M isoproterenol-stimulated cAMP levels.
Adrenal and vascular tyrosine hydroxylase activity in Goldblatt hypertension.
Authors: Rauch A L , Campbell W G
Published: June 2012

To examine the role of the sympathetic nervous system in hypertension, the in vitro activity of tyrosine hydroxylase was examined in one-kidney, one clip (1K1C) and two-kidney, one clip (2K1C) hypertensive rabbits and their respective controls 2 weeks after surgical procedures. The in vitro activity of tyrosine hydroxylase provides a measure of catecholamine synthesis and serves as a biochemical index of activity of noradrenergic neurons and the adrenal medulla. Mean atrial pressure rose from 91.5 +/- 1.0 to 128.5 +/- 5.6 mm Hg (p less than 0.01) in the 1K1C group and from 91.8 +/- 1.3 to 106.5 +/- 5.0 mm Hg (p less than 0.02) in the 2K1C group, whereas no change in blood pressure was found in their respective controls. Adrenal tyrosine hydroxylase activity was increased 85% in the 1K1C group, as compared with values in one-kidney controls (from 11.8 +/- 1.5 to 21.8 +/- 1.1 pmol CO2/min/mg; p less than 0.0002), and was increased 49% in the 2K1C group, as compared with values in two-kidney controls (from 8.01 +/- 1.2 to 11.9 +/- 1.1 pmol CO2/min/mg; p less than 0.02). In the 1K1C group, proximal mesenteric tyrosine hydroxylase activity was decreased 46% compared with values in one-kidney controls (from 23.5 +/- 5.0 to 12.8 +/- 2.5 pmol CO2/min/mg; p less than 0.03) and distal mesenteric tyrosine hydroxylase activity was decreased 42% (from 7.73 +/- 1.2 to 4.46 +/- 0.8 pmol CO2/min/mg; p less than 0.03). In the 2K1C group, neither proximal nor distal mesenteric tyrosine hydroxylase activity was altered. Tyrosine hydroxylase activity was not detectable in the femoral arteries, or in the thoracic and abdominal aorta.(ABSTRACT TRUNCATED AT 250 WORDS)
Age and blood pressure changes. A 20-year follow-up study in nuns in a secluded order.
Authors: Timio M , Verdecchia P , Venanzi S , Gentili S , Ronconi M , Francucci B , Montanari M , Bichisao E
Published: June 2012

In a prospective study, 144 white nuns belonging to a secluded monastic order and 138 white control laywomen were followed for 20 years to investigate whether living for a long time in a stress-free environment influences the effect of aging on blood pressure. Silence, meditation, and isolation from society are the distinctive features of the life-style examined. At study entry, blood pressure was not dissimilar in the nuns and the control group, but it increased over time only in the controls, with a mean slope of the regression line (beta coefficient) of 0.089 in the nuns (NS) and 2.171 in the controls (p less than 0.0001) for systolic blood pressure and of 0.054 in the nuns (NS) and 0.742 in the controls (p less than 0.0001) for diastolic blood pressure. Weight and body mass index increased similarly over time in the two groups. Family history of hypertension was not dissimilar between the groups. Serum cholesterol and triglycerides, higher at study entry in the nuns, increased similarly over time in the two groups. Twenty-four-hour urinary sodium excretion, collected randomly in both groups, did not differ over time between nuns and controls. None of the women smoked or used oral contraceptives. Educational level was higher in the control group, but subgroups of 48 nuns and 52 laywomen of comparable educational level maintained the same difference in the blood pressure trend over time as in the main cohort. Parity affected the increase of systolic, but not of diastolic, blood pressure with age among the laywomen, but nuns and no-childbirth controls maintained a significantly different blood pressure trend over time.(ABSTRACT TRUNCATED AT 250 WORDS)
Mediators produced by the endothelial cell.
Authors: Gryglewski R J , Botting R M , Vane J R
Published: June 2012

This review discusses the role of three mediators, synthesized by vascular endothelial cells, that help to keep the surface of the normal endothelium nonthrombogenic. The first is prostacyclin, a product of arachidonic acid metabolism discovered in 1976. This labile prostanoid, with a half-life of approximately 3 minutes, relaxes vascular smooth muscle and inhibits the aggregation of blood platelets. Prostacyclin and its analogues are currently being tested clinically for use in cardiovascular diseases such as primary pulmonary hypertension. The second mediator discussed is endothelium-derived relaxing factor (EDRF), discovered in 1980, which also relaxes smooth muscle and inhibits the aggregation and adhesion of platelets. Substances that stimulate the release of EDRF include acetylcholine, bradykinin, and adenosine 5'-diphosphate. EDRF is even more labile than prostacyclin, with a half-life of about 6 seconds, and it has recently been identified as nitric oxide. Prostacyclin and EDRF are released together following stimulation of endothelial receptors and synergize to inhibit platelet aggregation. 13-Hydroxy-9,11-octadecadienoic acid, a third suggested mediator, is not released but acts from inside the cell to make the endothelial surface nonadhesive for circulating blood cells. It is proposed that these three mediators form the endothelial defense mechanism against blood-borne cells and chemicals and that breakdown of this barrier results in diseases such as hypertension and atherosclerosis.
Relationship of dietary sodium, potassium, calcium, and magnesium with blood pressure. Belgian Interuniversity Research on Nutrition and Health.
Authors: Kesteloot H , Joossens J V
Published: June 2012

From 1979 through 1984, a randomized epidemiological survey in Belgium assessed the dietary intake of sodium, potassium, calcium, and magnesium using 24-hour food records checked by trained dietitians. Dietary cation intake levels were correlated with blood pressure both in the total group (4167 men and 3891 women) and in the group not taking antihypertensive medication (3814 men and 3329 women). Serum sodium, potassium, calcium, and phosphorus were also measured. Multiple regression analysis adjusting for age, body mass index, heart rate, alcohol intake, and total caloric intake revealed a significant positive correlation between sodium intake and blood pressure in the group not treated for hypertension except for diastolic blood pressure in women. A significant negative correlation was found between dietary calcium intake and diastolic blood pressure in men and between dietary magnesium intake and systolic blood pressure in women. No independent effect of dietary potassium intake on blood pressure could be established. Significant but weak correlations were found between the dietary intake of sodium, potassium and calcium and their serum values. The study confirms the hypothesis that at the population level dietary cations are related to the regulation of blood pressure.
A gene for high urinary kallikrein may protect against hypertension in Utah kindreds.
Authors: Berry T D , Hasstedt S J , Hunt S C , Wu L L , Smith J B , Ash K O , Kuida H , Williams R R
Published: June 2012

The inheritance of 12-hour overnight total urinary kallikrein excretion and its association with family history of essential hypertension were studied in 405 normotensive adults and 391 youths in 57 Utah pedigrees. Total urinary kallikrein excretion was highly familial with 51% of the total variance attributable to a dominant allele for high total urinary kallikrein excretion and 27% attributable to the combined effects of polygenes and shared family environment. An estimated 28% of the population has one or two copies of the dominant allele for high total urinary kallikrein excretion (2.3 SD units higher than the low homozygotes). About 83% of the population could be assigned to one of the two genotypic populations. Individuals with the high total urinary kallikrein excretion genotype were significantly less likely to have one or two hypertensive parents (relative odds = 0.56, p = 0.042). We conclude that a dominant allele expressed as high total urinary kallikrein excretion may be associated with decreased risk of essential hypertension. Further studies should be performed to confirm this finding and to test for interactions between this apparently protective gene and other genetic and environmental determinants of essential hypertension.
Left ventricular function and collagen content after regression of hypertensive hypertrophy.
Authors: Motz W , Strauer B E
Published: June 2012

To determine whether regression of hypertensive hypertrophy through blood pressure control also involves left ventricular collagen and consecutive alterations in left ventricular diastolic and systolic function, antihypertensive treatment with the calcium channel blocker nifedipine (30 mg/kg.day) was employed in 20-week-old spontaneously hypertensive rats (n = 15) for a period of 20 weeks. Age-matched (40 weeks old) untreated (n = 13) and 20-week-old spontaneously hypertensive rats representing the state before therapy (n = 14) were used for comparison. Myocardial stiffness was described by the tangent modulus Km of the elastic stiffness-stress relation. Left ventricular collagen was determined by means of hydroxyproline (OH-proline) concentration. Myocardial working capacity of the left ventricle was measured as the peak developed systolic pressure per weight unit muscle mass and systolic peak pump function as the maximum achievable cardiac output under volume loading. After the 20-week course of nifedipine treatment, systolic aortic pressure dropped from 187 +/- 11 to 144 +/- 6 mm Hg (p less than 0.001). Regression of hypertrophy was shown by a left ventricular muscle/body weight ratio of 2.13 +/- 0.18 mg/g (p less than 0.01) in the 40-week-old nifedipine-treated hypertensive rats, whereas the ratios of the 20-week-old and 40-week-old untreated spontaneously hypertensive rats were 2.3 +/- 0.30 and 2.34 +/- 0.18 mg/g, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanical properties of carotid arteries from DOCA hypertensive swine.
Authors: Kamm K E , Gerthoffer W T , Murphy R A , Bohr D F
Published: June 2012

Carotid arteries from control and deoxycorticosterone acetate (DOCA) hypertensive swine were examined for alterations in structure and in contractile properties. Vessels were excised 7 weeks after subcutaneous implantation of the steroid and subsequent elevation in mean arterial pressure from 102 to 133 mm Hg. The carotid media was 1.8 times thicker in arteries from hypertensive animals than in arteries from control animals. This enlargement was associated with an increase in muscle mass, as the fraction of the media composed of smooth muscle cells remained unchanged. Maximal active stress induced by several agonists normalized for cell cross-sectional area was unaltered. No change was observed in sensitivity or maximal response to norepinephrine, histamine, or KCl depolarization. Isotonic shortening rates were also comparable, as was the time course of shortening velocity to a constant afterload during tonic contractions. It is concluded that an enlargement of the carotid media develops in this model of hypertension. However, this response is not associated with detectable alterations in contractile system function.
Effect of oral calcium on blood pressure response in salt-loaded borderline hypertensive patients.
Authors: Saito K , Sano H , Furuta Y , Fukuzaki H
Published: June 2012

To clarify the mechanism of the antihypertensive effect of oral calcium loading, we studied the effect of low versus high calcium intake on salt-induced blood pressure elevations in patients with borderline hypertension. After a 7-day period of dietary salt restriction (50 meq/day), 27 patients were placed on a high salt (300 meq/day), low calcium (250 mg/day) diet for 7 days; 14 of these patients were given 2,160 mg/day of supplementary calcium (Ca group), and 13 patients were given placebo (non-Ca group). With a high salt intake, the percent increase in mean blood pressure was smaller in the Ca group than in the non-Ca group (+2.85 +/- 1.22% vs. +8.63 +/- 1.66%, respectively, p less than 0.01). The Ca group showed a smaller weight gain (p less than 0.05) and a greater urinary excretion of sodium (p less than 0.005) than the non-Ca group. In the Ca group, but not in the non-Ca group, high salt intake resulted in an increase in intraerythrocyte magnesium content (p less than 0.01), which was correlated inversely with the salt-induced changes in mean blood pressure (r = -0.54, p less than 0.05). While the increase in cellular magnesium was greater in the Ca group, the changes in red blood cell sodium and sodium/potassium ratio were not different between the two groups. The results suggest that oral calcium supplementation may prevent a rise in blood pressure in patients on a high salt, low calcium diet by attenuating the sodium retention.(ABSTRACT TRUNCATED AT 250 WORDS)
Epidermal growth factor responsiveness in smooth muscle cells from hypertensive and normotensive rats.
Authors: Scott-Burden T , Resink T J , Baur U , Bürgin M , Bühler F R
Published: June 2012

Aortic smooth muscle cells from spontaneously hypertensive rats (SHR) exhibit inappropriate proliferation characteristics in culture that suggest a modified response to serum mitogens or growth factors. The present study compares vascular smooth muscle cells from SHR and normotensive Wistar-Kyoto (WKY) rats with respect to their proliferative and functional response to growth factors. Specific attention was focused on the interaction of these vascular smooth muscle cells with epidermal growth factor. An increased growth rate of vascular smooth muscle cells from SHR (vs. WKY rats) was observed when cells were cultured in the presence of serum (10% and 0.5%), but not under serum-free conditions. The additional presence of low serum concentrations (0.5%) was required for epidermal growth factor to elicit a proliferative response, whereupon smooth muscle cells from SHR displayed an increased (vs. WKY rats) growth rate. Saturation binding of [125I]epidermal growth factor to intact smooth muscle cells indicated a twofold increase in receptor density in SHR-derived cells (p less than 0.001 vs. WKY rats) without an alteration in affinity for the growth factor. Cells derived from SHR also exhibited greater functional responsiveness to epidermal growth factor when compared with smooth muscle cells from WKY rats as evidenced by amplifications of both S6 kinase activation, phosphoinositide catabolism, elevation of intracellular pH, and DNA synthesis (nuclear labeling). We conclude that increased responsiveness of SHR-derived smooth muscle cells to epidermal growth factor could contribute to alterations in vascular smooth muscle growth and tone that may be fundamental to the pathogenesis of hypertension and atherosclerosis.
Blunted pressure natriuresis in the Brattleboro diabetes insipidus rat.
Authors: Gonzalez-Campoy J M , Awazu M , Granger J P , Haas J A , Romero J C , Knox F G
Published: June 2012

Antidiuretic hormone is known to stimulate the renal synthesis of prostaglandins. These autacoids, in turn, modulate the pressure natriuresis phenomenon. Accordingly, the present study was done to test the hypothesis that, in the absence of antidiuretic hormone and antidiuretic hormone-dependent prostaglandin synthesis, the pressure natriuresis response is blunted. Experiments were performed on Brattleboro diabetes insipidus rats (n = 7) and Long Evans control rats (n = 14). A change in perfusion pressure in the Long Evans rats from 89.3 +/- 1.0 to 108.7 +/- 1.1 mm Hg (p less than 0.05) was associated with significant increases in the fractional excretion of sodium (1.1 +/- 0.2 to 2.3 +/- 0.3%) and the urinary prostaglandin excretion (32.6 +/- 6.8 to 56.6 +/- 10.0 pg/min). In contrast, a similar change in perfusion pressure in the diabetes insipidus rat from 88.6 +/- 1.4 to 106.2 +/- 1.5 mm Hg (p less than 0.05) resulted in no significant increases in either sodium or prostaglandin excretions. Treatment of a third group of diabetes insipidus rats (n = 9) with 1-desamino-8-D-arginine vasopressin (1 microgram/day) restored the natriuretic response to increases in renal perfusion pressure. Treated diabetes insipidus and Long Evans control rats had comparable natriuretic responses to increases in renal perfusion pressure. Untreated diabetes insipidus rats, on the other hand, had blunted responses. In summary, the pressure natriuresis response in diabetes insipidus rats is blunted compared with Long Evans control rats. We conclude that antidiuretic hormone is necessary for the complete expression of the pressure natriuresis response.
Cardiovascular regulatory functions in elderly patients with hypertension.
Authors: Kawamoto A , Shimada K , Matsubayashi K , Chikamori T , Kuzume O , Ogura H , Ozawa T
Published: June 2012

To dissociate the effects of an elevated blood pressure on the cardiovascular regulatory functions from those of aging in the hypertensive elderly individual, resting hemodynamic measurements and circulatory autonomic functions in 30 elderly (mean age, 66 years) hypertensive (World Health Organization stages I and II) patients were compared with those in 30 healthy elderly (mean age, 65 years) normotensive volunteers. The elderly hypertensive group showed a significantly lower cardiac index and higher total peripheral resistance. beta-Receptor sensitivity, as determined by chronotropic dose of infused isoproterenol, and baroreceptor reflex sensitivity index, derived from phase II, but not phase IV, of Valsalva's maneuver, were only slightly but significantly reduced in the hypertensive group. The variability of heart rate at rest as an index of parasympathetic control of heart was similar between these two groups. Plasma norepinephrine level was significantly inversely related to resting mean blood pressure (r = -0.31, p less than 0.05) when analyzed as a whole group. Plasma renin activity, but not plasma aldosterone, was significantly decreased in the hypertensive group. To define the effects of age itself, these parameters in normotensive elderly subjects were also compared with those in 12 young normotensive subjects (mean age, 23 years). Although resting hemodynamic measurements did not differ, various circulatory autonomic functions were significantly different between these two age groups. The variability of heart rate in 24-hour ambulatory monitoring, beta-receptor responsiveness, resting vagal cardiac activity, and baroreceptor reflex sensitivity derived from phase IV of Valsalva's maneuver were significantly depressed in the elderly. Resting plasma norepinephrine level was elevated and renin-aldosterone system decreased in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)
Hyposecretion of atrial natriuretic factor by prehypertensive Dahl salt-sensitive rat.
Authors: Onwochei M O , Rapp J P
Published: June 2012

Studies were carried out to determine if the release of atrial natriuretic factor (ANF) is altered in the inbred Dahl salt-sensitive (SS/Jr) rat. Isolated heart-lung preparations of prehypertensive young SS/Jr rats (6-8 weeks of age) and age-matched inbred Dahl salt-resistant (SR/Jr) rats were used. At this relatively young age the blood pressure difference between strains (SS/Jr, 108 +/- 3 mm Hg; SR/Jr, 103 +/- 2 mm Hg) was minor. ANF release was stimulated with preload-induced or afterload-induced atrial stretch. Increased preload produced increases in right and left atrial pressures that were equivalent between young SS/Jr and SR/Jr rats; increased afterload produced increases only in left atrial pressures, which again were equivalent for young rats of the two strains. At any preload-induced change in atrial pressure SS/Jr rat hearts released less ANF than those of SR/Jr rats. Similarly, at any afterload-induced increase in left atrial pressure, SS/Jr rat hearts released less ANF than those of SR/Jr rats. In contrast to the above results in young rats, the strain differences were dramatically reversed when older rats (5-6 months of age) were used; at this age SS/Jr rats were markedly hypertensive (SS/Jr, 211 +/- 8 mm Hg; SR/Jr 130 +/- 4 mm Hg). Hearts from adult hypertensive SS/Jr rats released more ANF than hearts from adult normotensive SR/Jr rats at any left atrial pressure as afterload was increased. This reversal of SS/Jr rats from hyposecreters to hypersecreters of ANF is probably a consequence of hypertension-induced changes such as cardiac hypertrophy and recruitment of the ventricles to produce ANF. It is concluded that the hyposecretion of ANF by prehypertensive SS/Jr rats may represent a genetic trait relevant to the pathogenesis of genetic hypertension and that this is obscured by adaptive changes in the heart as hypertension progresses.
Chronic inhibition of angiotensin converting enzyme decreases Ca2+-dependent tone of aorta in hypertensive rats.
Authors: Sada T , Koike H , Nishino H , Oizumi K
Published: June 2012

Long-term effects of a novel angiotensin converting enzyme (ACE) inhibitor, CS-622, on Ca2+-dependent tone in aortic smooth muscles of spontaneously hypertensive rats (SHR) were examined. CS-622 (3 or 10 mg/kg/day), when orally administered to SHR for 21 weeks, exhibited a dose-dependent antihypertensive action. In Krebs-Henseleit solution, removal of Ca2+ caused much greater relaxation in aortas excised from control SHR than those from SHR treated with CS-622. Restoration of Ca2+ from zero to 2.5 mM elicited a marked contraction in aortas from control SHR but only a small contraction in aortas from both CS-622-treated SHR and normotensive Wistar-Kyoto rats. These findings suggested that myogenic tone that resulted from increased Ca2+ permeability in aortas of SHR was suppressed by long-term treatment with CS-622. The aortic tone from the individual rats correlated well with systolic blood pressure in both CS-622-treated and control SHR. The exaggerated myogenic tone in aortas of SHR was attenuated in the medium containing nicardipine but was not altered in the presence of CS-622 diacid (active form of CS-622) at a concentration high enough to fully inhibit aortic ACE. The myogenic tone in normal Ca2+ concentration was not decreased in aortas excised from SHR treated with hydralazine (5 mg/kg/day) for 21 weeks. We conclude that after prolonged administration CS-622 reduced the high vascular tension resulting from increased Ca2+ permeability of vascular smooth muscle membrane in SHR and that the restoration of normal Ca2+ permeability of vascular smooth muscles may underlie long-term antihypertensive action of ACE inhibitors.
Nisoldipine inhibition of sodium influx into aorta from aldosterone-salt-hypertensive rats.
Authors: Smith J M , Cragoe E J , Jones A W
Published: June 2012

The purpose of this study was to determine whether increased sodium (Na) influx into the aorta was associated with aldosterone-salt hypertension in the rat and, if present, to determine what mechanisms contributed to the increase. Basal 24Na influx was elevated in aorta from the hypertensive rats (2.21 +/- 0.10 mmol/l cell H2O/min, n = 25) compared with control-salt rats (1.75 +/- 0.04 mmol/l cell H2O/min, n = 24). The calcium (Ca) antagonist nisoldipine inhibited the Na influx into aorta from hypertensive rats in a concentration-dependent manner. At 10 nM nisoldipine, the Na influx in hypertensive rats (1.52 +/- 0.14 mmol/l cell H2O/min, n = 10) was similar to control rats (1.66 +/- 0.18 mmol/l cell H2O/min, n = 7). The basal Na influx in aorta from hypertensive rats was not altered by dichlorobenzamil or ethylisopropylamiloride, selective inhibitors of Na-Ca and Na-H exchange, respectively. The Na influx was 2.21 +/- 0.10, 2.03 +/- 0.24, and 2.11 +/- 0.19 mmol/l cell H2O/min for basal (n = 25), dichlorobenzamil (n = 4), and ethylisoproisopropylamiloride (n = 11), respectively. Inhibition of Na influx in hypertensive rats by 0.1 microM nisoldipine (delta Na influx = -0.72 +/- 0.18 mmol/l cell H2O/min, n = 9) was not significantly altered when applied with dichlorobenzamil (-0.72 +/- 0.21 mmol/l cell H2O/min, n = 4) or ethylisopropylamiloride (-0.55 +/- 0.15 mmol/l cell H2O/min, n = 11). These agents did not alter Na influx in control aorta.(ABSTRACT TRUNCATED AT 250 WORDS)
Long-term improvement in renal function after short-term strict blood pressure control in hypertensive nephrosclerosis.
Authors: Pettinger W A , Lee H C , Reisch J , Mitchell H C
Published: June 2012

Seventy-nine hypertensive nephrosclerosis patients entered a prospective randomized single-blind study to 1) establish the pattern of decay of renal function in this population and the variability therein and 2) to determine if strict diastolic blood pressure (DBP) control (less than or equal to 80 mm Hg) is more effective than conventional levels (90-95 mm Hg) in conserving renal function. Because of unexpected significant improvement in renal function in patients from both groups, which changed the perspectives on the course of this disease as described herein, this report is being published before completion of the trial. The selection criteria were 1) serum creatinine concentration of 1.6-7.0 mg/dl, 2) glomerular filtration rate of less than 70 ml/min/1.73 m2, and 3) absence of diseases (other than hypertension) known to destroy renal function. Renal function was assessed by glomerular filtration rate [( 125I]iothalamate clearance) and serum creatinine concentration. Before randomization, DBP was aggressively treated to reduce it to less than 80 mm Hg. Twenty-two subjects (14 in the strict DBP control group and eight in the conventional DBP control group) have been enrolled in the study for 36 months. In contrast to results from previous studies in humans and rats, renal function improved in both patient groups. Thus, irrevocable progression of renal damage after onset of renal failure from high blood pressure does not necessarily occur, and in fact, long-term improvement of renal function resulted from the effects of the study itself.(ABSTRACT TRUNCATED AT 250 WORDS)
Atrial natriuretic factor effects on cyclic nucleotides in a human renal cell line.
Authors: Cole F E , Rovigatti U , Iwata T , Vaughn J , Frohlich E D
Published: June 2012

The natriuretic effects of atrial peptide hormones have been attributed, at least in part, to their stimulation of guanylate cyclase activity in renal cell membranes. The effects of atrial natriuretic factor (ANF) on stimulation of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) accumulation were investigated in cloned human kidney tumor (hKT) cells and parent cells from a human renal tumor epithelial cell line (SK-NEP-1). Human ANF-(99-126) (10(-6)M) stimulated (p less than 0.001) cellular cGMP accumulation in a dose-dependent manner from a basal level of 0.26 +/- 0.04 to 3.73 +/- 0.81 pmol/mg protein/5 mi (mean +/- SEM, n = 13). ANF stimulation of cGMP accumulation was specific, in that high concentrations (10(-6)M) of atriopeptin I [rat ANF-(103-123)], angiotensin II, arginine vasopressin, and amiloride (10(-4)M) did not increase basal cGMP. Amiloride (10(-4)M) enhanced (p less than 0.01, n = 6) the ANF stimulation of cGMP accumulation (1.24 +/- 0.39 pmol/mg protein/5 min), particularly at low doses of ANF (10(-10)M) where stimulation by ANF without amiloride (0.34 +/- 0.08 pmol/mg protein/5 min) was barely distinguishable from a basal level (0.19 +/- 0.02 pmol/mg protein/5 min) of cGMP accumulation. The stimulatory effect of ANF (1.59 +/- 0.07 pmol/mg protein/5 min) was attenuated (0.75 +/- 0.06 pmol/mg protein/5 min, p less than 0.01, n = 6) by preincubation of the cells with pertussis toxin but not by cholera toxin. ANF (4.56 +/- 0.93 pmol/mg protein/5 min, n = 8) did not affect cAMP accumulation (4.32 +/- 0.98 pmol/mg protein/5 min) in hKT cells. This is the first report of an ANF responsive human renal cell line, and its use should facilitate investigation of ANF-receptor interactions.