bluuebunny/crossref_metadata_2025 huggingface dataset:
Converting-enzyme inhibitor administration lowers urinary free 19-nor-deoxycorticosterone levels.
Authors: Griffing G T , Wilson T E , Melby J C
Published: June 2012

19-Nor-deoxycorticosterone (19-nor-DOC) is a human mineralocorticoid. The regulation of its secretion is poorly understood, as renin angiotensin II (ANG II) stimulation has minimal effects on 19-nor-DOC. This study sought to determine if ANG II inhibition would decrease 19-nor-DOC production. Six normal subjects on fixed electrolyte intake were admitted to a metabolic unit. After a 5-day control period to establish electrolyte balance, enalapril, p.o., 10 mg/day, was administered for 28 days. This treatment resulted in ANG II inhibition, which was reflected by a rise in plasma renin activity, a blunting of the postural plasma aldosterone increment, and a decrease in aldosterone secretion rate (ASR). Levels of urinary free (UF) 19-nor-DOC progressively decreased from 294 +/- 108 ng/day on Day 0 to 164 +/- 70 on Day 3, 141 +/- 62 on Day 7, 101 +/- 38 on Day 14, 68 +/- 18 on Day 21, and 106 +/- 31 on Day 28. The decrease in 19-nor-DOC levels was synchronous with the fall in ASR (R = 0.94, n = 5, p less than 0.005), but it was of greater magnitude (71% decrease in 19-nor-DOC levels versus 41% decrease in ASR). In addition, the decrease in 19-nor-DOC levels correlated with a fall in urinary potassium and an increase in both urinary sodium and chloride (R = 0.68, -0.79, -0.87 respectively; n = 6, p less than 0.05). The fall in ASR, on the other hand, was not significantly correlated with the changes in these urinary electrolyte levels (R = 0.65, 0.64, 0.57 respectively; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)
Vascular reactivity in the spontaneously hypertensive rat. Effect of high pressure stress and extracellular calcium.
Authors: Field F P , Soltis E E
Published: June 2012

The role of extracellular calcium and high blood pressure stress in altered vascular adrenergic responsiveness in rings of femoral artery from spontaneously hypertensive rats (SHR) was investigated. A model in which partial ligation of the external iliac artery prevents the increase in blood pressure to the ipsilateral femoral artery was used to assess the effect of the increase in pressure stress on these alterations. Age-matched (5-week-old) male Wistar-Kyoto rats (WKY) and SHR were used in the study. Partial ligation was performed before a substantial increase in blood pressure occurred (6 weeks of age), and studies on vascular reactivity were carried out at 10 to 12 weeks of age when the SHR were considered hypertensive (indirect systolic blood pressure greater than 150 mm Hg). Maximal contractility of rings of unprotected femoral artery from the SHR in response to KCl in either a normal (2.5 mM) or low (0.25 mM) calcium Krebs solution was significantly greater (p less than 0.05) than was that of protected vessels from the SHR or protected and unprotected vessels from the WKY; however, no difference in the sensitivity to KCl was observed. Isoproterenol-induced relaxation was significantly attenuated in rings of vascular smooth muscle from unprotected femoral arteries of the SHR (p less than 0.05), while the responses of protected vessels from the SHR were similar to controls. Equilibration of vascular smooth muscle in a low calcium Krebs solution resulted in an increase in beta-adrenergic mediated relaxation in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Application of immunochemical methods to the identification and characterization of rat kidney inactive renin.
Authors: Takii Y , Figueiredo A F , Inagami T
Published: June 2012

Identification of inactive prorenin in the kidney has been difficult due to rapid proteolytic conversion of the inactive zymogen to its active form in the tissue or during homogenization and purification. Immunochemical methods, Western blotting, direct radioimmunoassay, and immunoaffinity chromatography were used to isolate and identify rat kidney renin and prorenin and to determine their molecular weights without complete purification. Antisera to pure rat renin were raised in rabbits. A specific reaction between the antisera and rat renin was demonstrated by double immunodiffusion, inhibition of enzyme activity, and competitive radioimmunoassay. The anti-rat renin IgG did not cross-react with purified human renin or rat spleen or kidney cathepsin D. The IgG showed binding affinity to both inactive renin as well as active enzyme. A combination of affinity chromatographies consisting of pepstatin-Sepharose, IgG-Sepharose, and Affi-Gel Blue permitted rapid and complete separation of inactive renin from active renin in rat kidney extract. Neither inactive nor active renin preparations exhibited aspartyl protease activity on hemoglobin used as substrate. The apparent molecular weight of inactive renin was estimated as 50,000 by gel filtration. Electrophoresis of partially purified inactive renin in sodium dodecyl sulfate (SDS) polyacrylamide gel followed by transblotting of proteins to a nitrocellulose sheet and immunochemical staining with anti-renin IgG showed a single protein band with a molecular weight of 48,000. Activation of inactive renin by trypsin was accompanied by the reduction of the 48,000-dalton native protein to a 39,000-dalton protein as determined by the SDS polyacrylamide gel electrophoresis and the transblotting.(ABSTRACT TRUNCATED AT 250 WORDS)
Vasopressin contributes to hypertension caused by nucleus tractus solitarius lesions.
Authors: Sved A F , Imaizumi T , Talman W T , Reis D J
Published: June 2012

Lesions of the nucleus tractus solitarius (NTS) were studied to determine whether they elevate plasma vasopressin levels and, if so, whether these elevated levels of vasopressin contribute to the hypertension caused by NTS lesions. Bilateral electrolytic lesions of the NTS caused acute, severe hypertension in rats anesthetized with chloralose and in conscious, freely moving rats. After placement of the NTS lesions there was a greater than tenfold elevation in plasma vasopressin levels. Administration of an antagonist of the vasoconstrictor action of vasopressin markedly diminished the hypertension in both conscious and anesthetized rats. Following ganglionic blockade with chlorisondamine, NTS lesions still elicited hypertension, and the magnitude of the hypertension was not different from that observed in rats not treated with chlorisondamine. The hypertension produced by lesions of the NTS in ganglionic-blocked rats was completely abolished by administration of a vasopressin antagonist. These results indicate that (1) NTS lesions elevate plasma vasopressin levels and (2) elevated plasma vasopressin contributes to the hypertension produced by such lesions.
Cyclic guanosine monophosphate mediates vascular relaxation induced by atrial natriuretic factor.
Authors: Ohlstein E H , Berkowitz B A
Published: June 2012

The biochemical mechanism of action of synthetic atrial natriuretic factor (atriopeptin II) was studied in vascular smooth muscle of the rabbit thoracic aorta. Atriopeptin II caused a time-dependent and concentration-dependent increase in tissue levels of cyclic guanosine monophosphate that corresponded in these same tissues with vascular relaxation. The elevation of arterial cyclic guanosine monophosphate levels preceded the onset of vascular relaxation. Atriopeptin II did not alter vascular levels of cyclic adenosine monophosphate. The presence of a functionally intact vascular endothelium was not necessary for atriopeptin II to elicit vascular relaxation. Atriopeptin II-induced vascular relaxation and elevation of cyclic guanosine monophosphate levels were inhibited by the guanylate cyclase inhibitor methylene blue. These data suggest cyclic guanosine monophosphate mediates vascular relaxation produced by atriopeptin II.
Autoregulation and vasoconstriction in the intestine during acute renal hypertension.
Authors: Meininger G A , Routh L K , Granger H J
Published: June 2012

The purpose of this study was to investigate whether local mechanisms of blood flow autoregulation mediate vasoconstriction during the early development of renal hypertension. Anesthetized rats were instrumented with Doppler flow probes on the celiac (CA), superior mesenteric (SMA), and renal arteries to measure flow velocity in these vessels. Acute two-kidney, one clip renal hypertension was produced by inflating a pneumatic occluder on the left renal artery to reduce flow velocity by 50%. Two hours after renal artery stenosis (RAS), femoral artery pressure (AP) was increased by 35%, CA resistance by 45%, and SMA resistance by 57%. No increases were observed in AP or in CA and SMA resistances for sham-operated, control rats. To determine if autoregulation contributed to the increase in SMA resistance, we protected the SMA vasculature from the increased arterial pressure by servocontrolled inflation of a pneumatic cuff implanted around the SMA. Although normalizing SMA pressure with the protective cuff significantly reduced (p less than 0.05) the increase in SMA resistance that occurred after RAS, SMA resistance remained elevated above control levels. These results suggest that (1) reduced intensity of SMA constriction produced by protection of the SMA is due to inhibition of a local autoregulatory mechanism that is contributing to the increase in SMA resistance during the acute development of renal hypertension, and (2) maintenance of elevated SMA resistance during protection from increased AP is the result of pressure-independent mechanisms that are activated subsequent to renal artery stenosis.
Cerebral autoregulation in young spontaneously hypertensive rats. Effect of sympathetic denervation.
Authors: Sadoshima S , Fujishima M , Yoshida F , Ibayashi S , Shiokawa O , Omae T
Published: June 2012

Autoregulation of cerebral blood flow was studied with the hydrogen clearance method during development of hypertension in young spontaneously hypertensive rats. To examine the influence of sympathetic nerves on autoregulatory range, the unilateral superior cervical ganglion was removed 2 hours or 2 or 5 weeks before the study. Wall-to-lumen ratio of cerebral arteries was determined with freeze substitution technique. Basal blood pressures were 87 +/- 1 mm Hg (mean +/- SEM) at 4 weeks of age, 105 +/- 2 at 6 weeks, and 126 +/- 3 at 9 weeks, although resting cerebral blood flow was unchanged. Initially, cerebral blood flow remained relatively constant when the blood pressure was raised by intravenous infusion of phenylephrine. The upper limits of cerebral blood flow autoregulation in these groups were 110 +/- 4 mm Hg, 126 +/- 7, and 159 +/- 6 respectively. Acute ganglionectomy significantly lowered the upper limits (p less than 0.05), but chronic denervation did not affect the autoregulatory range. The wall-to-lumen ratios of cerebral arteries were 0.136 +/- 0.007 at 4 weeks and 0.130 +/- 0.005 at 9 weeks. These differences were not significant, nor did sympathetic denervation alter the ratio. These results indicate that (1) the upward shift of the autoregulation is closely related to a rise in the basal blood pressure, (2) acute interruption of sympathetic nerves modulates the autoregulatory range, and (3) adaptation of cerebral blood flow autoregulation to early developmental hypertension may be attributed to factors other than vascular smooth muscle hypertrophy.
Calcium channel blockade with nitrendipine. Effects on sodium homeostasis, the renin-angiotensin system, and the sympathetic nervous system in humans.
Authors: Luft F C , Aronoff G R , Sloan R S , Fineberg N S , Weinberger M H
Published: June 2012

To test the hypothesis that the antihypertensive effect of the calcium channel blocking drug nitrendipine is in part related to natriuresis, we gave 16 subjects (8 normal, 8 hypertensive) placebo for 8 days followed by nitrendipine titrated to 20 mg twice daily for 8 days. The same diet was prepared for each meal for the entire study. Sodium intake was fixed for each subject and averaged 150 mEq/day. All urine was collected every day. Blood was drawn at the end of the placebo and nitrendipine periods for renin, aldosterone, and norepinephrine values. Nitrendipine caused a significant increase (p less than 0.05) in cumulative sodium excretion of 161 mEq over 7 days in the normal subjects and 103 mEq in hypertensive subjects. Potassium excretion was unaffected. In both hypertensive and normal subjects, plasma renin and plasma norepinephrine activity increased significantly (p less than 0.05), while plasma aldosterone levels did not change. Upright systolic blood pressure decreased significantly (p less than 0.05) in both groups, whereas upright diastolic blood pressure decreased only in hypertensive subjects. We conclude that blood pressure lowering effects of this drug may be in part related to natriuresis and that calcium channel blockade may dissociate plasma renin activity from that of aldosterone.
Hypertension in hypoglycemic diabetics treated with beta-adrenergic antagonists.
Authors: Ryan J R , LaCorte W , Jain A , McMahon F G
Published: June 2012

To evaluate the response during insulin-induced hypoglycemia, diabetics treated with relatively selective or nonselective beta-adrenergic blocking agents were studied. Placebo, atenolol (100 mg/day), and propranolol (80 mg b.i.d.) were administered to 12 insulin-treated diabetics for 1 week in a double-blind, randomized, crossover fashion with a 2-week washout between treatments. Sufficient intravenous insulin (0.2-0.6 units/kg) was administered to decrease plasma glucose 68% from the basal level or to less than 60 mg/dl within 90 minutes. Blood pressure changes at the nadir of plasma glucose were +15.2/-9.9 mm Hg for placebo, +27.9/0 mm Hg for atenolol, and +38.8/+14.3 mm Hg for propranolol. Diastolic blood pressure changes induced by propranolol were significantly different from those induced by atenolol (p less than 0.01) and placebo (p less than 0.01), and systolic pressure changes were significantly different (p less than 0.02) between propranolol and atenolol. Mild seizures developed in two patients treated with propranolol. Their blood pressure changes at the plasma glucose nadir were +56/+22 and +86/+31 mm Hg. Other symptoms of hypoglycemia were more frequent during beta-blocker than during placebo treatment. Differences in response may be related to the relatively selective adrenergic blocking effect of these drugs.
Overall and regional hemodynamic effects of leukotriene D4 in spontaneously hypertensive rats.
Authors: Zukowska-Grojec Z , Bayorh M A , Kopin I J , Feuerstein G
Published: June 2012

Leukotriene D4, a constituent of slow-reacting substance of anaphylaxis, elicits a pressor response followed by hypotensive shock in spontaneously hypertensive rats but not in other rats. Hemodynamic mechanisms underlying this pattern in spontaneously hypertensive rats, pithed and vagotomized to eliminate circulatory reflexes, were studied using radiolabeled microspheres. One minute after leukotriene D4 administration (20 micrograms/kg i.v.), mean arterial pressure increased by 54 mm Hg, total peripheral resistance index increased by 68%, heart rate decreased by 34 beats/minute, and cardiac index was unchanged. Profound reductions of blood flow and increases of vascular resistance in the hepatosplanchnic area, skeletal muscles, and skin also occurred. Five minutes later, mean arterial pressure remained elevated (+35%), hematocrit rose (+17%), and total peripheral resistance index increased, which offset 40% decreases in cardiac and stroke volume indices. Ten minutes after leukotriene D4 administration, during hypotension, cardiac and stroke volume indices and blood flow to all vascular beds declined further while total peripheral resistance index and hematocrit (+28%) continued to rise. In Wistar-Kyoto rats, administration of leukotriene D4 caused less of a pressor response (+34 mm Hg) because vascular resistance was increased only in skeletal muscles, which was followed by a slight hypotension without any significant changes in cardiac and stroke volume indices, total or regional vascular resistance, and hematocrit. Thus, in spontaneously hypertensive rats the leukotriene D4-induced pressor response appears to be caused by generalized vasoconstriction, and the subsequent hypotension appears to result not from vascular collapse but from reduced cardiac output.
Hypertension in experimental diabetes mellitus. Renin-prostaglandin interaction.
Authors: Katayama S , Lee J B
Published: June 2012

To investigate mechanisms involved in the high incidence of hypertension in diabetes mellitus, the relationship between renin-angiotensin production and renal prostaglandin E2 synthesis was studied in rats 1 week after diabetes mellitus had been induced by streptozotocin injection. The diabetic rats became hypertensive, although plasma renin activity did not increase despite the plasma volume contraction resulting from polyuria and natriuresis. Subcutaneous insulin injection resulted in a marked increase in plasma renin activity, while more rigid control of diabetes mellitus achieved by constant insulin infusion decreased blood pressure. Cortical renin content and renin release as well as papillary prostaglandin E2 synthesis in vitro were significantly lower in diabetic rats than in nondiabetic controls. Isoproterenol and prostaglandin E2 stimulated renin release in controls, while diabetic rats responded only to isoproterenol. Insulin infusion by pump reversed these abnormalities. An additive effect of a maximum dose of isoproterenol (10(-5) M) and prostaglandin E2 (10(-4) M) on renin release was observed in nondiabetic controls and in diabetic rats treated with insulin pump, but not in untreated diabetic rats. The results suggest that 1) renal renin release and prostaglandin E2 synthesis in diabetes mellitus are insulin dependent, 2) inappropriately lower plasma renin activity in diabetes mellitus may be attributed to a diminished renal renin pool and a lack of renin release in response to renal prostaglandin E2, the synthesis of which is also impaired in diabetes, prostaglandin E2-induced renin release may operate independently from isoproterenol-induced renin release, and impaired renal prostaglandin E2 synthesis may contribute to the development of hypertension in the face of an unchanged prohypertensive renin-angiotensin II system.
The relative contribution of body fat and fat pattern to blood pressure level.
Authors: Weinsier R L , Norris D J , Birch R , Bernstein R S , Wang J , Yang M U , Pierson R N , Van Itallie T B
Published: June 2012

Although the association between body weight and blood pressure is irrefutable, body fat mass and blood pressure level may not necessarily be directly related. To clarify the relative contribution of fat mass to blood pressure level, we analyzed data on 399 adults consecutively entering a weight control program. Although most subjects were notably overweight (mean ideal body weight 177%), the population represented a wide spectrum of body weights and blood pressure levels. Study parameters included body fat mass (by total body water, 40K, and Steinkamp formula), lean body mass, body build (chest to height ratio), fat cell number and size from bilateral buttock biopsy specimens, upper fat pattern by arm to thigh circumference ratio, and central fat pattern by subscapular to triceps skinfold ratio. Our results concurred with previously noted correlations between obesity and blood pressure (as mean arterial pressure): weight (r = 0.44), percentage of body fat (r = 0.19), and absolute fat mass (r = 0.38; all p less than 0.01); however, lean body mass, age, and body build correlated highly with both fat mass and mean arterial pressure, thereby confounding this relationship. Multivariate analysis was performed to evaluate the relative contribution of fat mass to mean arterial pressure in the presence of these and other potentially confounding variables. Lean body mass, age, body build, and an upper body fat pattern were found to contribute significantly to the variation in mean arterial pressure (p less than 0.01). In their presence, percentage of body fat, absolute fat mass, central fat pattern, fat cell characteristics, and age of onset of obesity did not significantly improve the predictability of mean arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Percutaneous transluminal renal angioplasty in nonatherosclerotic renovascular hypertension. Long-term results.
Authors: Millan V G , McCauley J , Kopelman R I , Madias N E
Published: June 2012

Nineteen stenotic arteries in 16 patients with severe renovascular hypertension of nonatherosclerotic nature (fibromuscular dysplasia in 13, neurofibromatosis in 3) were treated with percutaneous transluminal renal angioplasty. The procedure was technically successful in 12 of 14 (86%) stenoses in the fibromuscular dysplasia subgroup but in only one of five (20%) lesions in the neurofibromatosis subgroup. Hypertension was abated (3 patients) or disappeared (8 patients) in 11 of the 12 (92%) patients with fibromuscular dysplasia who had a technically successful angioplasty, an effect that was sustained at latest follow-up (avg, 37 mo; range, 10-73 mo). The only complication encountered was a retroperitoneal hematoma that resolved uneventfully. Coupled with those from other centers, the results of the present study indicate that angioplasty offers a strong potential for curability in patients with renovascular hypertension caused by fibromuscular dysplasia and that percutaneous transluminal renal angioplasty should be considered the treatment of choice for the initial management of all patients with fibromuscular renovascular hypertension.
Blood pressure changes during adolescence and subsequent adult blood pressure level.
Authors: Woynarowska B , Mukherjee D , Roche A F , Siervogel R M
Published: June 2012

Serial data were analyzed for blood pressure recorded between the ages of 9 to 18 years for 278 children and for a subset of this group whose blood pressure was measured at the age of 30 +/- 5.0 years (n = 93). Blood pressures were measured by auscultation over the antecubital fossa with the participant seated. Systolic blood pressure was recorded when the first sound was heard, and diastolic blood pressure was recorded when all sounds disappeared (fifth phase). A linear regression model was fitted to the data for each individual, and adjustments were made for regression toward the mean using maximum likelihood procedures. There were no significant correlations between the estimated initial values of blood pressure and the rate of change from 9 to 18 years of age. The associations between the levels of blood pressure at 9 years of age and at 30 years of age were significant for systolic blood pressure only in male subjects and were not significant for diastolic blood pressure in either sex. The correlations between the rate of blood pressure change from 9 to 18 years of age and blood pressure levels at 30 years of age were nonsignificant. When the initial values and the rate of change in blood pressure from 9 to 18 years of age were taken into account simultaneously, they accounted for approximately 20% of the variation in systolic blood pressure levels at 30 years of age. This finding indicates that children with higher blood pressure levels at about 9 years of age and with rapid increases in blood pressure during pubescence may have an increased risk of becoming hypertensive.(ABSTRACT TRUNCATED AT 250 WORDS)
Inability of dorsal spinal rhizotomy to prevent renal wrap hypertension in rats.
Authors: Pan J Y , Bishop V S , Ball N A , Haywood J R
Published: June 2012

Renal hypertension has been shown to be prevented and reversed by renal denervation. It has been postulated that the afferent nerves from the kidney are responsible for mediating the hypertensive stimulus that activates the sympathetic nervous system and increases arterial pressure. This study was designed to directly test the hypothesis that the afferent renal nerves are necessary for the development and maintenance of renal hypertension. In the first experiment, dorsal spinal rhizotomies or sham rhizotomies were performed in rats between T9 and L1, through which afferent renal nerves have been shown to traverse. After the one-kidney, one-wrap procedure, the increase in systolic arterial pressure and water intake was similar in the two groups of rats. To determine whether the removal of afferent renal nerves reversed the hypertensive process, animals with established renal hypertension were subjected to dorsal rhizotomy or the sham-rhizotomy procedure. Again, there was no significant effect on systolic arterial pressure and water intake. Although combined dorsal and ventral rhizotomy and subdiaphragmatic vagotomy did not affect the onset of hypertension, spinal transection at the level of C8 effectively prevented the rise in arterial pressure. Although efferent neural mechanisms contribute to the hypertensive process, these studies suggest that afferent renal nerves are not directly involved in the development and maintenance of one-kidney, one-wrap renal hypertension.
Demonstration of a ouabainlike plasma compound in hypertension prone and hypertension resistant rats.
Authors: Lichtstein D , Minc D , Shimoni Y , Deutsch J , Mekler J , Ben-Ishay D
Published: June 2012

Material extracted and partially purified from plasma of the Sabra hypertension prone rats was found to be capable of 1) inhibiting the binding of 3H-ouabain to rat brain synaptosomes, 2) inhibiting the activity of rat brain microsomal Na, K activated adenosine triphosphatase, and 3) increasing the contractile force of rat heart muscle. The results demonstrate the presence of a ouabainlike compound in the plasma of these rats. The plasma concentration of this compound in Sabra hypertension prone rats was 698 +/- 199 nmol/ml in ouabain equivalents (SEM; n = 11) versus 2543 +/- 1140 nmol/ml (n = 9) in the Sabra normotensive strain. The presence of ouabainlike compound in the plasma is consistent with the hypothesis that this compound functions as a hormone that regulates Na, K activated adenosine triphosphatase activity and the physiological processes in which this enzyme is involved.
Cardiac mass and peripheral vascular structure in hydralazine-treated spontaneously hypertensive rats.
Authors: Jespersen L T , Nyborg N C , Pedersen O L , Mikkelsen E O , Mulvany M J
Published: June 2012

We have examined the effect of antihypertensive treatment on heart weight and on structural and functional characteristics of isolated mesenteric resistance vessels (internal diameter 170-220 micron) in spontaneously hypertensive rats (SHR) and in Wistar-Kyoto rats (WKY). The SHR and WKY were treated with hydralazine from the age of 4 weeks and were examined at ages 12 to 14 weeks and 23 to 27 weeks. Treated SHR had a mean blood pressure as much as 29% below that of control WKY, which in turn was 25 to 40% less than that of control SHR. In 12- to 14-week-old rats the heart to body weight ratio (which in control SHR was 13% greater than of WKY) was unaffected by treatment. Thereafter, the heart to body weight ratio of treated SHR did not increase as much as usual. At both ages, the media thickness and contractile response of the resistance vessels of the SHR (which were, respectively, 37% and 30% greater than those of vessels of WKY) were unaffected by treatment. However, because treatment caused a small (8%) increase in the lumen diameter of the vessels of the SHR, treatment did cause small, but possibly physiologically important, decreases both in the media to lumen ratio (11%) and in the pressure against which these vessels would have been able to contract (10%). Treatment had little effect on the pharmacological characteristics of vessels of either SHR or WKY. The results suggest that the increased heart weight, media thickness, and contractile response in mesenteric resistance vessels of SHR up to ages 23 to 27 weeks are due primarily to factors other than increased pressure.
Angiotensinogen levels in the brain and cerebrospinal fluid of the genetically hypertensive rat.
Authors: Healy D P , Printz M P
Published: June 2012

The present experiments were designed to document changes in the regional distribution of angiotensinogen in the rat brain with the development of hypertension in spontaneously hypertensive rats (SHR) relative to age-matched normotensive Wistar-Kyoto rats (WKY). Levels of angiotensinogen were measured in discrete brain nuclei and cerebrospinal fluid from rats at 4, 7, and 16 weeks of age and in cerebrospinal fluid obtained by cisternal puncture at 7 and 16 weeks. Age-dependent changes in angiotensinogen were found, with levels higher in both strains at 4 weeks of age compared with 7 or 16 weeks. In contrast, plasma levels of angiotensinogen were essentially the inverse of the brain levels, low at 4 weeks and higher at 7 and 16 weeks. Levels in a number of regions adjacent to the rostral third ventricle from the 4-week-old SHR (prehypertensive phase) were significantly elevated relative to the WKY (p less than 0.05), while levels in the amygdala and posterior hypothalamus were significantly lower in the SHR (p less than 0.05). In 7-week-old rats (evolving phase), levels in nine brain regions were significantly elevated in the SHR relative to the WKY and included the nucleus tractus solitarii (p less than 0.01). Unlike the prehypertensive and evolving phases, in 16-week-old rats (maintenance phase) only two brain areas, the nucleus of the diagonal band and the lateral hypothalamus, had significantly elevated levels in the SHR (p less than 0.05). Cerebrospinal fluid levels of angiotensinogen did not correlate well with brain levels of angiotensinogen.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac beta-adrenergic receptors in salt-dependent genetic hypertension.
Authors: Limas C , Limas C J
Published: June 2012

The pattern of cardiac beta-adrenergic receptor changes in different hypertrophy models varies according to the pathophysiology. In salt-sensitive Dahl rats, high dietary salt intake leads to a moderate degree of cardiac hypertrophy associated with increased numbers of cardiac beta-adrenergic receptors but unchanged affinity for agonists. Isoproterenol-stimulated cardiac adenylate cyclase is also higher in salt-loaded hypertensive rats without any change in basal or NaF-stimulated activities. In contrast, neither beta-adrenergic receptors nor adenylate cyclase activities are affected by variations in dietary salt in salt-resistant Dahl rats. The extent of isoproterenol-induced down regulation of beta-adrenergic receptors on isolated cardiac myocytes as well as the recovery from this down regulation is not significantly different in either strain of Dahl rats and is not influenced by dietary salt. The enhancement of beta-adrenergic pathways in salt-dependent genetic hypertension may be involved both in the initiation of cardiac hypertrophy and the preservation of contractile function.
Endogenous opiate peptides, stress reactivity, and risk for hypertension.
Authors: McCubbin J A , Surwit R S , Williams R B
Published: June 2012

Endogenous opiate peptides can regulate neuroendocrine and circulatory responses to behavioral stress and may be important in the pathogenic effects of sympathoadrenal reactivity. We tested this hypothesis by examining the effect of the opiate antagonist naloxone on blood pressure responses to behavioral stress in young adults with high, medium, or low casual blood pressures. Naloxone increased mean arterial pressure responses to stress in subjects with low casual pressure, but had no significant effect on responses in subjects with high casual pressure. These results suggest opioidergic inhibition of sympathetic nervous system responses may be deficient in persons at risk for essential hypertension.
Dissociation of 24-hour catecholamine levels from blood pressure in older men.
Authors: Stern N , Beahm E , McGinty D , Eggena P , Littner M , Nyby M , Catania R , Sowers J R
Published: June 2012

Increased plasma norepinephrine levels have been observed in some persons with early essential hypertension. Although both plasma norepinephrine level and mean arterial blood pressure rise with age, little is known about the state of catecholamine secretion in elderly patients with essential hypertension. We studied the 24-hour cycle levels of plasma norepinephrine, epinephrine, and dopamine in 12 elderly hypertensive subjects and 13 age-matched normotensive controls (mean ages, 63.8 +/- 1.2 yr and 64.8 +/- 1.8 yr [SEM] respectively). Blood samples were obtained at bihourly intervals from 0900 to 2100 hours and every 30 minutes from 2100 to 0900 hours, during which time sleep and breathing were continuously monitored. A circadian rhythm was displayed in both groups by plasma epinephrine levels (mesor, 49 +/- 2 pg/ml and 38 +/- 1 pg/ml; amplitude, 15 +/- 2 pg/ml and 11 +/- 1 pg/ml; acrophase, 12.20 +/- 0.40 hr and 14.41 +/- 0.34 hr in the normotensive and hypertensive groups respectively) but not by plasma norepinephrine or dopamine levels. During the 24-hour cycle plasma epinephrine, but not norepinephrine or dopamine, levels were positively related to mean arterial blood pressure (r = 0.60 for the normotensive subjects, r = 0.57 for the hypertensive subjects, p less than 0.01 for both).(ABSTRACT TRUNCATED AT 250 WORDS)
Lymphocyte abnormalities in three types of hypertension in the rat.
Authors: Furspan P B , Bohr D F
Published: June 2012

Lymphocyte number and weight and their sodium and potassium contents and net passive fluxes were measured in spontaneously hypertensive stroke-prone rats, deoxycorticosterone acetate-treated rats, and two-kidney, one clip renal hypertensive rats. Wistar-Kyoto rats were used as controls for the spontaneously hypertensive stroke-prone rats, and normal intact Sprague-Dawley rats were used as controls for the others. Blood lymphocyte count was higher and lymphocyte weight was lower in the hypertensive rats. Intralymphocytic sodium content (millimoles per kilogram of dry weight) was elevated in the three forms of hypertension as compared with control values (spontaneously hypertensive stroke-prone rats, 43.0 +/- 1.7 vs Wistar-Kyoto rats, 37.3 +/- 1.3; deoxycorticosterone acetate-treated rats, 44.4 +/- 3.1 vs Sprague-Dawley rats, 36.1 +/- 1.7; one-kidney, one clip rats, 50.5 +/- 3.7 vs Sprague-Dawley rats, 38.9 +/- 2.0). Intralymphocytic potassium content was not significantly altered in any of the forms of hypertension. Lymphocytes from spontaneously hypertensive stroke-prone rats and deoxycorticosterone acetate-treated rats exhibited elevated net sodium fluxes (millimoles per kilogram of dry weight per hour) as compared with those of controls (spontaneously hypertensive stroke-prone rats, 7.00 +/- 0.99 vs Wistar-Kyoto rats, 4.89 +/- 0.63; deoxycorticosterone acetate-treated rats, 7.58 +/- 0.97 vs Sprague-Dawley rats, 5.6 +/- 0.64). Net potassium fluxes were significantly elevated only in the spontaneously hypertensive stroke-prone rats (14.07 +/- 1.70 vs 8.23 +/- 1.04 in Wistar-Kyoto rats). Sodium and potassium fluxes in lymphocytes from two-kidney, one clip rats and Sprague-Dawley rats were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
Direct measurement of sodium influx in vascular smooth muscle. Stimulation by aldosterone.
Authors: Menard M R , Friedman S M
Published: June 2012

The influx of 22Na into the smooth muscle cells of incubated rat tail arteries was measured directly, in the presence and absence of 2.8 X 10(-7) M D-aldosterone. During the analysis, extracellular 22Na and 23Na were removed by incubation of the tissue in sodium-free lithium-substituted physiological salt solution at less than 3 degrees C. Aldosterone increased the influx rate coefficient by 10% (0.104 +/- 0.004 [SE] min-1, n = 13, vs 0.095 +/- 0.003 [SE] min-1, n = 13 without aldosterone; p less than 0.01) but did not significantly reduce the sodium content. We conclude from direct measurements that aldosterone acts to increase the influx of sodium in incubated tail arteries from normal rats; we conclude from measurements of the sodium influx and sodium content that aldosterone also acts to increase the efflux of sodium in this preparation.
Angiotensin-producing serum enzyme II. Formation by inhibitor removal and proenzyme activation.
Authors: Haas E , Lewis L V , Scipione P , Koshy T J , Varde A U , Renerts L
Published: June 2012

A highly active angiotensin-producing enzyme (enzyme II) was obtained from dog serum by acid treatment and fractionation to remove angiotensinase and converting enzyme, separate an inhibitor, and convert an inactive precursor (proenzyme II) to enzyme II. Proenzyme II was found to be converted to enzyme II by an endogenous activating enzyme identified as plasmin. Conversion was also caused by the interaction of bacterial streptokinase with human proactivator, by trypsin, and by an activator formed from liver tissue extract and dog serum. Neither plasma kallikrein nor the labile, human extrinsic tissue-type plasminogen activator induced activation. The inhibitor, which normally blocks the activation of proenzyme II, was unusually stable against high temperatures and extremes of pH, and it was not identical to any of the six known protease inhibitors of serum. Enzyme II was not identical to other angiotensin-producing enzymes such as enzyme I, renin, cathepsin D, pepsin, plasmin, tonin, or cathepsin G. Enzyme II reacted maximally at pH 4.7 and produced up to 2250 ng of angiotensin I/ml serum/hr from the substrate of dog serum (i.e., amounts 3200-fold higher than that produced by endogenous renin of normal dog serum). Since at pH 7.2, angiotensin I formation is still about 30 times higher than that of renin, enzyme II may be physiologically active under some conditions.
Crucial role of endothelium in the vasodilator response to increased flow in vivo.
Authors: Pohl U , Holtz J , Busse R , Bassenge E
Published: June 2012

Experiments were designed to investigate the importance of vascular endothelium in the vasomotor response to increases in flow as observed in conduit arteries (flow-dependent dilation). The diameter changes of femoral arteries (sonomicrometry) in response to increases in flow before and after endothelial damage procedures were studied in 23 dogs anesthetized with sodium pentobarbital. The functional integrity of the endothelial cells underneath the diameter sensors was tested by intra-arterial acetylcholine (local acetylcholine dilation) applied proximally to the sensors while a constant flow was maintained. Unilateral augmentation of femoral arterial flow (4.6 +/- 1.9-fold) induced by peripheral vasodilation or by arteriovenous shunt, elicited dilation (increase in diameter, 116 +/- 91 microns) in 18 of 23 dogs, whereas the diameter of the contralateral control artery was not affected. Mechanical removal of the endothelial cells by means of a balloon catheter abolished both the flow-dependent dilation and the local acetylcholine dilation, whereas the vasomotor responses to norepinephrine and nitroglycerin were not affected. Brief perfusions (1 minute) of the arteries with cell-free hydrogen peroxide solution (90 mM) also abolished the flow-dependent dilation and attenuated the local acetylcholine dilation (by 27 +/- 19%; p less than 0.02), while the responses to norepinephrine and nitroglycerin were not altered. These results suggest that endothelial cells act as mediators of flow-dependent dilation.
Evidence against the role of calcium deficiency in genetic hypertension.
Authors: Lau K , Gafter U , Rydell D , Eby B , Pesigan M , Tropp I , Garno J , Zikos D
Published: June 2012

Epidemiological studies suggest an association between reduced calcium uptake and hypertension, while clinical trials and rat experiments indicate a small but significant hypotensive effect with oral calcium supplements. These data imply that calcium deficiency has a role in genetic hypertension. We reasoned that if the hypothesis is correct, the hypertension should be aggravated by further reducing calcium balance but attenuated by augmenting calcium balance. We tested this hypothesis by evaluating the blood pressure response in spontaneously hypertensive rats (SHR) as calcium balance was decreased by dietary restriction of calcium or increased by supplementation with magnesium or 1 alpha, 25-dihydroxycholecalciferol (calcitriol). A low calcium diet within the physiological range did not accentuate the hypertension in SHR during the 11 weeks of treatment, even though calcium balance was reduced by half. Similar results were obtained with dietary calcium restriction in parathyroidectomized SHR, which excludes any offsetting effects of changes in parathyroid hormone levels. Conversely, 7 weeks of a high magnesium diet, which increased calcium balance without reducing PO4 balance, did not correct the hypertension of SHR. Similarly, long-term administration of calcitriol failed to reduce the blood pressure of parathyroidectomized SHR and normotensive Wistar-Kyoto (WKY) controls, despite the presence of increased serum calcium levels comparable to those produced by oral calcium loading. Finally, external calcium balance was measured directly in 25-day-old, prehypertensive SHR. As a result of the increased calcium absorption and reduced calcium excretion, SHR retained more calcium than did the normotensive WKY, which directly refutes the existence of calcium deficiency at this normotensive stage. These data do not support the role of calcium deficiency in genetic hypertension.
Effects of sodium chloride on pregnant sheep with reduced uteroplacental perfusion pressure.
Authors: Leffler C W , Hessler J R , Green R S , Fletcher A M
Published: June 2012

This study investigated the effects of NaCl supplementation (5 mEq/kg/day) on the arterial pressure of pregnant and nonpregnant sheep with and without reduction of uteroplacental perfusion pressure. In pregnant sheep receiving NaCl supplementation during the third trimester, reduction of aortic pressure caudal to the kidneys to 65% of the upstream pressure (occlusion) caused a progressive increase in mean arterial pressure from 89 +/- 3 to 110 +/- 3 mm Hg over 2 weeks. Occlusion was accompanied by a decrease in urine flow. Six of seven sheep died or were killed because of severe respiratory distress. No abnormalities were detected in nonpregnant sheep or pregnant sheep receiving NaCl supplementation only. Pregnant sheep that were occluded but received no supplementary NaCl did not become hypertensive but aborted about 2 weeks after occlusion. These results indicate that reduction of uteroplacental perfusion pressure causes hypertension in NaCl-supplemented pregnant sheep but not in sheep receiving a normal, low sodium diet.
Hemodynamic characteristics of the intestinal microcirculation in renal hypertension.
Authors: Meininger G A , Fehr K L , Yates M B , Borders J L , Granger H J
Published: June 2012

This study investigated the microvascular changes that affect vascular resistance in the rat small intestine during two-kidney, one clip renal hypertension 4 weeks after renal artery stenosis. To study the intestinal microcirculation, a loop of the small intestine was exteriorized with intact circulation and innervation and a section of the bowel wall was prepared for observation with an intravital video microscopy system. Microvascular diameter, pressure, and flow velocity were measured for first, second, and third branch order arterioles and venules, using an image shearing monitor, servo-null micropipette system, and an optical Doppler velocimeter, respectively. The diameters of the first order arterioles and venules were significantly (p less than 0.05) reduced in hypertensive rats; however, diameters were unaltered in smaller second and third order arterioles and venules as compared with normotensive vessels. In hypertensive rats, mean arterial pressure was significantly (p less than 0.05) elevated (47%) and pressures also were elevated significantly (p less than 0.05) throughout the microcirculation, although by a proportionally smaller amount. Total network flow (i.e., first order arteriole flow) was significantly (p less than 0.05) reduced (40%) in hypertensive rats, but volume flows in individual second and third order arterioles were similar to flows measured in normotensive rats. Calculated total network resistance was increased (124%) in hypertensive rats. Thus, the intestinal microcirculation in rats with two-kidney, one clip renal hypertension is disturbed by elevated pressure and decreased total flow. The presence of normal flows in individual second and third order arterioles without any demonstrable difference in their diameters suggests that the predominant cause of elevated resistance across this segment of the intestinal microcirculation is a reduction in the number of perfused small arterioles.
Childhood familial pheochromocytoma. Conflicting results of localization techniques.
Authors: Turner M C , DeQuattro V , Falk R , Ansari A , Lieberman E
Published: June 2012

Childhood familial pheochromocytoma was investigated in four patients by abdominal computed tomographic scan, [131I]metaiodobenzylguanidine scan, and vena caval catecholamine sampling. Results conflicted with surgical findings. Computed tomographic scan identified all four adrenal tumors but missed two midline tumors in one patient. [131I]metaiodobenzylguanidine scan identified two of three adrenal tumors but also suggested extra-adrenal tumors not confirmed at operation in two of three patients. Vena caval sampling for catecholamines confirmed all adrenal tumors but suggested additional tumors not verified at operation in two of three patients. All patients are asymptomatic and have normal urinary catecholamines 15 to 51 months after operation. Because of the frequency of multiple tumors in familial pheochromocytoma, different diagnostic techniques were employed. False-positive results were more frequent with [131I]metaiodobenzylguanidine and vena caval sampling. Reinterpretation of the [131I]metaiodobenzylguanidine scans at a later date led to less false-positive interpretation, although the false-negative rate remained unchanged. More pediatric experience with [131I]metaiodobenzylguanidine scans and vena caval sampling in familial pheochromocytoma is needed. Confirmation of tumor and its localization rest with meticulous surgical exploration.
Genetic association of hypertension and vascular changes in stroke-prone spontaneously hypertensive rats.
Authors: Bruner C A , Myers J H , Sing C F , Jokelainen P T , Webb R C
Published: June 2012

Isolated tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP) exhibit oscillatory contractile activity in response to norepinephrine, whereas those from normotensive Wistar-Kyoto rats (WKY) do not. To determine whether the norepinephrine-induced oscillations are related to high blood pressure or to separable genetic differences between strains, the response to norepinephrine was studied in adult SHRSP, WKY, and progeny of genetic crosses of SHRSP and WKY (F1, F2, F1 X SHRSP, F1 X WKY). Helical tail artery strips were mounted in a tissue bath for isometric force recording. Rats were classified as responders if oscillatory activity in the presence of 1.8 X 10(-7) M norepinephrine exceeded 250 mg/10 min (milligrams of force amplitude during a 10-minute interval). The blood pressures (mm Hg +/- SEM; tail cuff method) and percentage of rats exhibiting norepinephrine-induced oscillations were as follows: WKY: 109 +/- 3, 0%; F1: 129 +/- 4, 0%; F2: 150 +/- 4, 38%; F1 X WKY: 137 +/- 3, 9%; F1 X SHRSP: 188 +/- 7, 71%; SHRSP: 207 +/- 7, 100%. The distribution of the frequency of animals with oscillatory activity among the progenies was consistent with the hypothesis that a single gene locus determines the observed difference in oscillatory activity between the WKY and SHRSP strains. The allele from the SHRSP that determines the activity phenotype is recessive to the allele contributed by the normotensive WKY strain. In the segregating F2 progeny, the blood pressure of the responders was higher than that of the nonresponders (161 +/- 6 vs 144 +/- 4 mm Hg; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)