bluuebunny/crossref_metadata_2025 huggingface dataset:
Thallium-201 stress imaging in hypertensive patients.
Authors: Schulman D S , Francis C K , Black H R , Wackers F J
Published: June 2012

To assess the potential effect of hypertension on the results of thallium-201 stress imaging in patients with chest pain, 272 thallium-201 stress tests performed in 133 hypertensive patients and 139 normotensive patients over a 1-year period were reviewed. Normotensive and hypertensive patients were similar in age, gender distribution, prevalence of cardiac risk factors (tobacco smoking, hyperlipidemia, and diabetes mellitus), medications, and clinical symptoms of coronary disease. Electrocardiographic criteria for left ventricular hypertrophy were present in 16 hypertensive patients. Stepwise probability analysis was used to determine the likelihood of coronary artery disease for each patient. In patients with mid to high likelihood of coronary disease (greater than 25% probability), abnormal thallium-201 stress images were present in 54 of 60 (90%) hypertensive patients compared with 51 of 64 (80%) normotensive patients. However, in 73 patients with a low likelihood of coronary disease (less than or equal to 25% probability), abnormal thallium-201 stress images were present in 21 patients (29%) of the hypertensive group compared with only 5 of 75 (7%) of the normotensive patients (p less than 0.001). These findings suggest that in patients with a mid to high likelihood of coronary artery disease, coexistent hypertension does not affect the results of thallium-201 exercise stress testing. However, in patients with a low likelihood of coronary artery disease, abnormal thallium-201 stress images are obtained more frequently in hypertensive patients than in normotensive patients.
Enhanced 5-hydroxytryptamine release from vascular adrenergic nerves in spontaneously hypertensive rats.
Authors: Kawasaki H , Urabe M , Takasaki K
Published: June 2012

The release of 5-hydroxytryptamine from the vascular adrenergic nerve by periarterial nerve stimulation in spontaneously hypertensive rats (SHR) was compared with that in normotensive Wistar-Kyoto rats (WKY). The isolated mesenteric vascular bed was perfused at a constant flow rate of 5 ml/min. Vasoconstrictor responses to periarterial nerve stimulation (4, 8, 12, and 16 Hz for 30 seconds) and 5-hydroxytryptamine (1 microM), but not norepinephrine (1 nmol), were significantly greater in SHR than in WKY. After treatment with 5-hydroxytryptamine (1 microM) for 15 minutes, vasoconstrictor responses to periarterial nerve stimulation previously reduced by prazosin (50 nM) were restored and a frequency-dependent pressor response reappeared. However, 5-HT treatment did not significantly affect the pressor response to exogenously administered norepinephrine (1 nmol), which was previously inhibited by prazosin. The degree of the restoration in SHR was significantly greater than that in WKY at all frequencies used. The restoration of the pressor response to periarterial nerve stimulation after 5-hydroxytryptamine treatment did not occur in the presence of the selective 5-hydroxytryptamine2 receptor antagonists ketanserin (10 nM) or LY53857 (10 nM). In the perfused mesenteric vascular bed of both WKY and SHR prelabeled with [3H]5-hydroxytryptamine, periarterial nerve stimulation (4-16 Hz) evoked a frequency-dependent increase in tritium efflux that was abolished by Ca2+-free Krebs-Ringer solution or tetrodotoxin (100 nM) and treatment with 6-hydroxydopamine. The tritium efflux evoked by periarterial nerve stimulation was significantly greater in SHR than in WKY at all frequencies used. These results suggest that the release of 5-hydroxytryptamine from adrenergic nerve endings by periarterial nerve stimulation is enhanced in the mesenteric vascular bed of the SHR.
Inhibition of muscle sympathetic nerve activity in humans by arginine vasopressin.
Authors: Floras J S , Aylward P E , Abboud F M , Mark A L
Published: June 2012

Arginine vasopressin, a potent vasoconstrictor, does not raise arterial pressure in normal humans even at pathophysiological plasma levels. To examine whether the pressor effect of vasopressin in humans is buffered by baroreceptor reflex inhibition of sympathetic nerve activity, we recorded postganglionic muscle sympathetic nerve activity directly from the peroneal nerve in 12 normal men before, during, and after a 20-minute intravenous infusion of vasopressin, 4 ng/kg/min, that increased mean plasma concentrations from 6.2 +/- 0.6 to 320 +/- 68 (SE) pg/ml. During the first 5 minutes (n = 8), mean arterial pressure increased from 91 +/- 3 to 97 +/- 4 mm Hg (p less than 0.05) and integrated sympathetic nerve activity decreased from 271 +/- 45 to 156 +/- 33 units (p less than 0.05). At 15 minutes (n = 12), arterial pressure did not differ from control values whereas forearm vascular resistance fell (p less than 0.05) and central venous pressure and heart rate increased (p less than 0.05). Sympathetic nerve activity remained below control levels throughout the infusion (202 +/- 31 vs 254 +/- 40 units before infusion; p less than 0.05). An effect of vasopressin on ganglionic transmission was excluded, since the sympathoexcitatory response to apnea was not attenuated during vasopressin. Thus, pathophysiologic levels of vasopressin in humans cause inhibition of muscle sympathetic nerve activity that is not due to a ganglionic blocking action. The sympathoinhibition may be caused in part by the modest increases in mean arterial and central venous pressures and attendant stimulation of arterial and cardiac baroreceptors. The reflex decrease in sympathetic nerve activity would be expected to buffer the direct vasoconstrictor effects of vasopressin.
Do hypertensive patients have a different diurnal pattern of electrolyte excretion?
Authors: Dyer A R , Stamler R , Grimm R , Stamler J , Berman R , Gosch F C , Emidy L A , Elmer P , Fishman J , Van Heel N
Published: June 2012

Studies generally indicate that excretion of sodium, potassium, and water is greater during the day than during the night. To determine whether hypertensive patients exhibit this same pattern of excretion, diurnal variations in excretion of sodium, potassium, creatinine, and water were examined in 107 hypertensive men and women from a clinical trial on control of hypertension by nonpharmacological means--the Hypertension Control Program. Each participant provided two carefully timed 24-hour urine collections divided into daytime and overnight specimens. The median ratios of 24-hour to 8-hour overnight excretion were 2.84, 3.95, 2.99, and 2.77 for sodium, potassium, creatinine, and water, respectively. Thus, more than half of this hypertensive group exhibited a greater rate of sodium and water excretion during sleep than during daytime hours, a reversal of the usual pattern. When the group was subdivided based on age, sex, race, trial randomization group, use of diuretics, and hypertension severity, women had significantly lower ratios of 24-hour to overnight excretion for sodium and water than men and blacks had significantly lower 24-hour to overnight ratios for water and potassium than whites. When the 24-hour to overnight ratios for these hypertensive patients were compared with those for a group of 30 men and women with high-normal blood pressure, those with high-normal blood pressure had significantly larger ratios for sodium and water excretion than the hypertensive group. The results of this study suggest that hypertensive patients may have a different diurnal pattern of sodium and water excretion than normotensive subjects and that further research is needed to clarify this issue.
Consequences of worksite hypertension screening. Changes in absenteeism.
Authors: Rudd P , Price M G , Graham L E , Beilstein B A , Tarbell S J , Bacchetti P , Fortmann S P
Published: June 2012

To confirm reports of increased absenteeism after worksite hypertension screening, we performed a three-stage blood pressure screening among 5888 self-selected heterogeneous workers at 11 electronics plants using standardized screening and labeling procedures. A total of 296 subjects with mean systolic blood pressure of 140 mm Hg or greater or diastolic blood pressure of 90 mm Hg or greater on all three occasions were considered to have sustained hypertension. From the untreated normotensive subjects matched for eight sociodemographic and occupational variables, we prospectively selected one to three controls for each sustained hypertensive subject. Uncorrected absenteeism rates for sustained hypertensive subjects increased 22% from baseline in the postscreening year. Correction by logarithmic transformation for skewed distributions and by rates for matched controls for temporal trends reduced these changes to statistical insignificance with high statistical power. Several subgroups exhibited trends to increased absenteeism. At 12-month follow-up, the blood pressure of the sustained hypertensive subjects showed mean decreases of 12.6/6.7 mm Hg (p less than 0.0001) after the majority had received pharmacological antihypertensive treatment. These results suggest that worksite hypertension screening and labeling produce insignificant absenteeism change overall among self-selected heterogeneous work force populations.
Nifedipine enhances the vasodepressor and natriuretic effects of atrial natriuretic peptide.
Authors: Seino M , Abe K , Nushiro N , Yoshinaga K
Published: June 2012

We examined a possible interaction between the calcium entry blocker nifedipine and atrial natriuretic peptide on blood pressure and natriuresis in anesthetized rabbits. The administration of atrial natriuretic peptide (0.05 micrograms/kg/min) produced a significant decrease in mean arterial pressure. Similar reductions in blood pressure were obtained during the administration of nifedipine (1.0 micrograms/kg/min). Atrial natriuretic peptide produced a consistent increase in glomerular filtration rate that was higher than the increase in renal blood flow; hence, the filtration fraction was significantly elevated. Atrial natriuretic peptide also elicited a significant increment in urine volume and urinary sodium excretion, while nifedipine was devoid of any significant effects on renal hemodynamics and renal excretory function during the experimental period. The administration of atrial natriuretic peptide superimposed on an ongoing infusion of nifedipine resulted in a greater fall of blood pressure than that seen during the administration of atrial natriuretic peptide or nifedipine alone. Sodium excretion was also potentiated, but there were no changes in renal hemodynamics or in the filtration fraction. These results suggest that calcium entry blockers potentiate the vasodepressor and the natriuretic effects of atrial natriuretic peptide but prevent its renal hemodynamic effects.
Abnormal regulation of adrenal angiotensin II receptors in spontaneously hypertensive rats.
Authors: Bradshaw B , Moore T J
Published: June 2012

The aldosterone response to angiotensin II is blunted in spontaneously hypertensive rats (SHR). To determine whether this blunting is due to a defect in angiotensin II receptors, we assessed angiotensin II binding to intact adrenal glomerulosa cells in SHR and normotensive Wistar-Kyoto rats (WKY) that had been fed high or low sodium diets before sacrifice. In rats on high salt intake, we observed no difference between the two strains in either receptor affinity (Kd = 1.0-1.2 nM) or binding capacity (36,000-38,000 receptors/cell). When sodium-restricted, WKY increased receptor content more than fourfold to 167,000 sites/cell. SHR increased receptor number to only 103,000 sites/cell, which was significantly (p less than 0.01) less than the WKY increase. The cause of the abnormal receptor regulation remains unclear. Two known receptor regulators, the plasma angiotensin II level and the state of potassium balance, were similar in the two strains. Our results suggest that the blunted aldosterone response to angiotensin previously reported in SHR is due to abnormal angiotensin receptor up-regulation in the adrenal gland in response to sodium restriction.
Factors influencing blood pressure and heart rate variability in hypertensive humans.
Authors: Floras J S , Hassan M O , Jones J V , Osikowska B A , Sever P S , Sleight P
Published: June 2012

We examined the influence of baroreceptor reflex sensitivity (the increase in pulse interval in response to a phenylephrine-induced increase in blood pressure), age, blood pressure, and beta-adrenergic receptor blockade on the variability of blood pressure and heart rate in essential hypertension. Fifty-six subjects were studied before treatment; intra-arterial blood pressure was recorded outside the hospital for 24 hours. Variability was defined (from all beats occurring while subjects were awake) as the standard deviation about the average waking value for mean arterial pressure (MAP) or pulse interval. The correlation (r) between baroreceptor reflex sensitivity and blood pressure variability was -0.47 (p less than 0.0002). Baroreceptor reflex sensitivity was the only independent determinant of blood pressure variability on multiple regression analysis. Thirty subjects were restudied after 5 months of beta-adrenergic receptor blockade. Ambulatory blood pressure was lower during treatment, whereas pulse interval, its variability, and baroreceptor reflex sensitivity were higher. Blood pressure variability was unchanged. The variability of MAP was inversely correlated with baroreceptor reflex sensitivity before (r = -0.42, p less than 0.02) and during (r = -0.45, p less than 0.02) treatment, but it was unrelated to the average ambulatory MAP or to the variability of pulse interval either before or during beta-blockade. Sixteen subjects whose average waking ambulatory blood pressure was 140/90 mm Hg or less were not treated. This group of borderline hypertensive subjects had less variable MAP than did the remaining 40 subjects (12.4 +/- 2.3 [SD] vs 14.5 +/- 2.5 mm Hg; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Plasma and urinary catecholamines in salt-sensitive idiopathic hypertension.
Authors: Gill J R , Güllner G , Lake C R , Lakatua D J , Lan G
Published: June 2012

Nineteen patients with normal renin idiopathic hypertension were arbitrarily classified as salt-sensitive or salt-resistant depending on whether their mean arterial pressure did or did not increase by 8% or more when sodium intake was increased. The responses of the two subsets and of five normal subjects to sodium intakes of 9, 109, and 249 mEq/day given for 7 days were as follows: The salt-sensitive subjects retained more sodium than normal and plasma or urinary norepinephrine did not decrease when they were given a high sodium intake; urinary dopamine was normal but did not increase normally when sodium intake was increased. The salt-resistant subjects excreted sodium normally and plasma and urinary norepinephrine was decreased by 30 and 37%, respectively, when they were given a high sodium intake; urinary dopamine was supernormal and did not increase further when sodium intake was increased. Cumulative sodium retention during the high sodium intake was directly related to the percentage of change in plasma norepinephrine in the hypertensive subjects, suggesting that renal adrenergic activity was a factor in the impaired sodium excretion in the salt-sensitive patients. Cumulative sodium retention and the percentage of change in plasma norepinephrine were inversely related to urinary dopamine in the hypertensive subjects, suggesting that increased formation of dopamine in renal and neural tissue in the salt-resistant subjects may have been responsible for the differences between the subsets in renal and adrenergic responses to a high sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS)
Functional versus structural changes of forearm vascular resistance in hypertension.
Authors: Schulte K L , Braun J , Meyer-Sabellek W , Wegscheider K , Gotzen R , Distler A
Published: June 2012

Structural changes in resistance vessels have been considered an important factor in triggering and maintaining chronic hypertension in humans and in experimental animals. To determine whether the increased forearm vascular resistance observed following vasodilator maneuvers in hypertensive patients is predominantly due to structural or to functional changes, we examined the influence of different vasodilator stimuli on forearm blood flow and blood pressure in 22 male patients with established essential hypertension and in 22 age-matched normotensive men (age range, 28-52 years). Blood pressure was measured directly, and blood flow was measured by venous occlusion plethysmography. The maneuvers applied were 1) arterial occlusion combined with handgrip exercise and local heating, 2) intra-arterial infusion of the calcium entry blocker nifedipine, 3) intra-arterial infusion of the nonspecific vasodilator sodium nitroprusside, 4) arterial occlusion initiated after intra-arterial infusion of nifedipine. Vascular resistance during vasodilation induced by arterial occlusion or infusion of nifedipine or sodium nitroprusside remained significantly higher in the hypertensive than in the normotensive subjects. However, the maximal vasodilation achieved by the combination of arterial occlusion and nifedipine resulted in a similar resistance in both groups (1.6 +/- 0.2 in the hypertensive vs 1.4 +/- 0.2 mm Hg/ml/min/100 ml tissue in the normotensive subjects. These data suggest that there is an important functional component of the elevated resistance in patients with essential hypertension.
Lingual epithelium of spontaneously hypertensive rats has decreased short-circuit current in response to NaCl.
Authors: Mierson S , Welter M E , Gennings C , DeSimone J A
Published: June 2012

Alterations in ion transport associated with hypertension have been found in a variety of organs. We used a modified Ussing chamber to compare the NaCl dependence of the short-circuit current across the dorsal lingual epithelium in vitro from spontaneously hypertensive rats (SHR) with that from Wistar-Kyoto rats (WKY). The short-circuit current in response to mucosal NaCl was less in SHR than in WKY at hyperosmotic concentrations (above 0.15 M and up to 2.0 M). Since ion transport in the lingual epithelium has been found to play a role in early events of salt taste transduction, the attenuation in the short-circuit current in hypertensive animals may be a factor in the enhanced salt preference of SHR compared with WKY.
Activation of the humoral antihypertensive system of the kidney increases diuresis.
Authors: Karlström G , Arnman V , Folkow B , Göthberg G
Published: June 2012

Isolated kidneys taken from normotensive Wistar-Kyoto rats were cross-perfused extracorporeally by normotensive strain-matched donor rats. The extracorporeal perfusion circuit was arranged so that the perfusion pressure to the normotensive recipient kidney could be varied from 90 to 200 mm Hg without any change in total flow through this circuit. This setup avoided hemodynamic or mechanical interferences with reflexogenic circulatory control in the normotensive donor rat when the recipient kidney was manipulated. Diuresis and natriuresis were measured in the normotensive donor rat and the normotensive recipient kidney. A few minutes after normotensive recipient kidney perfusion pressure had been raised, mean arterial pressure (MAP) and heart rate started to decline rapidly in the normotensive donor rat, and circulatory collapse ensued within 15 to 100 minutes. During the control period at 90 mm Hg normotensive recipient kidney perfusion pressure, urinary flow, MAP and heart rate were stable in the normotensive donor rat and the normotensive recipient kidney. When perfusion pressure was raised to 200 mm Hg in the recipient kidney, the urinary flow in the donor rat increased 62% on average in the first 10 minutes over values recorded before the pressure rise (p less than 0.05) while MAP simultaneously fell by 16% and HR remained unchanged. During the subsequent period, the urinary flow of the donor rat declined together with MAP and heart rate. In the extracorporeally high-pressure perfused recipient kidneys, an eightfold to ninefold increase in diuresis and natriuresis occurred during the first 45 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of the renin inhibitor A-64662 in monkeys and rats with varying baseline plasma renin activity.
Authors: Kleinert H D , Martin D , Chekal M A , Kadam J , Luly J R , Plattner J J , Perun T J , Luther R R
Published: June 2012

The efficacy of the potent, primate selective renin inhibitor A-64662 was studied in monkeys and rats with varying baseline plasma renin activity (PRA) to elucidate the relationship between PRA and the hypotensive response induced by this compound. The effect of a single bolus of vehicle or A-64662 at 0.001, 0.01, 0.1, 1.0, and 10.0 mg/kg i.v. was compared in 30 normal and 30 salt-depleted, anesthetized monkeys (n = 5/dose). Baseline mean arterial pressure (MAP) was similar among all groups, but baseline PRA was elevated in salt-depleted monkeys. A-64662 induced a comparable dose-related fall in MAP, affecting the magnitude and duration of action, accompanied by inhibition of PRA, the duration of which was dose-related in both the normal and salt-depleted groups. However, the minimum effective doses required to reduce MAP by approximately 10% were 0.01 mg/kg for the salt-depleted monkeys and 0.1 mg/kg for the normal monkeys. In a second study, three consecutive boluses of vehicle or A-64662 at 0.1, 1.0, and 10.0 mg/kg were administered to anephric monkeys, human renin-infused anephric monkeys, and normal monkeys (n = 4/group). A dose of 0.1 mg/kg was ineffective, but the 1.0 mg/kg dose lowered MAP by 11 +/- 3% (mean +/- SE) in the anephric monkeys. The infusion of renin into anephric monkeys restored the efficacy of A-64662 at the 0.1 and 1.0 mg/kg doses to responses comparable to those of the normal monkeys. A-64662 at 10.0 mg/kg caused a similar fall in MAP of 50 to 60% in anephric, renin-infused anephric, and normal monkeys in the absence of detectable PRA.(ABSTRACT TRUNCATED AT 250 WORDS)
The antihypertensive mechanism of verapamil. Alteration of glomerular filtration rate regulation.
Authors: Lin H B , Young D B
Published: June 2012

The renal hemodynamic and renin release responses to verapamil were analyzed to determine if the antihypertensive action of the calcium entry blocker could be due to its renal effects. Hemodynamic and renin release measurements were compared in a control group of nine anesthetized rabbits and in a group of 10 rabbits given verapamil (200 micrograms/kg i.v. initially, 4 micrograms/kg/min thereafter), starting 30 minutes before data collection. Measurements were made over a range of controlled renal perfusion pressure from 100 to 40 mm Hg. The renal blood flow at 100 mm Hg of the verapamil-treated group was 18% greater (p less than 0.02) than that of the control group, while the glomerular filtration rate was 51% greater (p less than 0.001) than that of the control group. Renal blood flow and glomerular filtration rate autoregulation were highly effective in the control group down to 80 mm Hg, but both variables were poorly regulated in the verapamil-treated group. The filtration fraction of the treated group was 36.9 +/- 1.5% versus 28.5 +/- 1.6% in the control group (p less than 0.003) at 100 mm Hg, and the filtration fraction of the treated group remained significantly greater down to 40 mm Hg. Renin release rates of the two groups were similar at the 100 mm Hg pressure level, but the increase in release due to the progressive reduction in perfusion pressure was significantly greater in the treated group than in the control group. At the 80 mm Hg pressure level, the mean release rate for the treated group was more than three times greater (p less than 0.05) than that of the control group. These findings demonstrate that verapamil is an effective renal vasodilator and that the effect is proportionally greater on the preglomerular than on the postglomerular resistance. This action could be the basis for its antihypertensive efficacy.
Genetics and salt modulate renal responses to atrial natriuretic factor.
Authors: Steele T H , Challoner-Hue L
Published: June 2012

We examined the consequences of genetic susceptibility or resistance to NaCl-induced hypertension and of prior salt loading (high or low NaCl intake) on the responses of isolated perfused Dahl salt-sensitive (DS) and Dahl salt-resistant rat (DR) kidneys to atriopeptin II. Atriopeptin II increased the glomerular filtration rate only in kidneys from high NaCl-fed rats, irrespective of their DS or DR status. Superimposition of norepinephrine on atriopeptin II further increased the glomerular filtration rate only in kidneys from low NaCl-fed rats (which had not reacted to atriopeptin II alone), irrespective of their DS or DR status, and did not change the glomerular filtration rate of high NaCl-fed rats. Norepinephrine alone, without atriopeptin II, uniformly decreased the glomerular filtration rate by about 80%. Atriopeptin II increased sodium excretion of high NaCl and low NaCl DR kidneys by more than five times as much as in the corresponding DS kidneys. Therefore, the glomerular filtration rate response to atriopeptin II varied globally with dietary NaCl, independently of genetic predisposition or resistance to NaCl-induced hypertension. The natriuretic response to atriopeptin II was blunted in kidneys from rats genetically susceptible to NaCl-induced hypertension, independently of their NaCl consumption. Atriopeptin II also ameliorated or reversed the adverse effect of norepinephrine on the glomerular filtration rate.
Hypertensive mechanisms associated with centrally administered aldosterone in dogs.
Authors: Kageyama Y , Bravo E L
Published: June 2012

The mechanism by which intracerebroventricularly administered aldosterone increases arterial pressure was investigated in trained, conscious dogs with cannulas chronically implanted in a lateral cerebral ventricle. In salt-replete and salt-depleted dogs, artificial cerebrospinal fluid with or without aldosterone (0.05 microgram/kg/hr) was infused intracerebroventricularly for 12 days by an osmotic minipump. A similar dose of aldosterone was infused subcutaneously for 12 days. Aldosterone infused intracerebroventricularly increased blood pressure significantly in both salt-replete and salt-depleted dogs. In salt-replete animals the hypertension was associated with increased total peripheral resistance without concomitant changes in blood volume, cardiac output, or in any of the neurohumoral parameters measured. We conclude that this type of hypertension is resistance-mediated from its outset and appears to be relatively independent of salt and water retention. The mechanism by which intracerebroventricularly administered aldosterone increases vascular resistance remains to be determined.
Vascular and sympathoadrenal responses to bradykinin and a bradykinin analogue.
Authors: Mulinari R , Benetos A , Gavras I , Gavras H
Published: June 2012

These experiments were designed to assess the interaction of bradykinin and its antagonist (Arg-Pro-Hyp-Gly-Phe-Ser-DPhe-Phe-Arg-trifluoroacetic acid) with the sympathoadrenal system. Three groups of male Wistar rats received 5-minute intra-arterial infusions of either dextrose (Group 1, n = 6), bradykinin, 250 micrograms/min (Group 2, n = 5), or bradykinin, 25 micrograms/min (Group 3, n = 4). Six other groups received a similar infusion of the bradykinin antagonist at 250 micrograms/min. They were either intact rats (Group 4, n = 10) or rats previously submitted to chemical sympathectomy (Group 5, n = 17), to adrenal enucleation (Group 6, n = 8), to combined alpha-adrenergic and beta-adrenergic blockade (Group 7, n = 7), to alpha 1-adrenergic receptor blockade (Group 8, n = 8), or to alpha 2-adrenergic receptor blockade (Group 9, n = 8). Bradykinin infusion produced a sustained fall in mean arterial pressure (MAP) in Groups 2 and 3 (by -48 +/- 3 and -36 +/- 7 mm Hg, respectively) associated with similar increases in plasma epinephrine levels (100-fold), and norepinephrine (sevenfold) as compared with Group 1. The bradykinin antagonist infusion in intact rats produced a 23 +/- 4 mm Hg rise in MAP associated with a sixfold increase in epinephrine and a twofold increase in norepinephrine. Group 5 rats with lower baseline catecholamine levels had an even larger MAP rise (30 +/- 6 mm Hg) accompanied by a rise in epinephrine and norepinephrine proportionally similar to that of intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Intralymphocytic sodium and free calcium and plasma renin in essential hypertension.
Authors: Oshima T , Matsuura H , Kido K , Matsumoto K , Fujii H , Masaoka S , Okamoto M , Tsuchioka Y , Kajiyama G , Tsubokura T
Published: June 2012

Intracellular sodium, potassium, and free calcium concentrations were investigated in lymphocytes of 30 patients with essential hypertension and 30 normotensive controls. All subjects were placed on a diet containing 8 to 10 g of sodium chloride per day. Lymphocyte sodium concentration was higher in hypertensive patients than in normotensive controls (19.8 +/- 1.8 vs 18.4 +/- 1.8 mmol/kg wet weight; p less than 0.01), whereas lymphocyte potassium concentration was similar in both groups. Lymphocyte free calcium concentration was also higher in hypertensive patients than in normotensive controls (134.6 +/- 13.2 vs 120.2 +/- 16.4 nmol/L; p less than 0.01). There was a positive correlation between lymphocyte sodium and free calcium concentrations in normotensive controls, in hypertensive patients, and in the subjects combined (r = 0.59, p less than 0.01; r = 0.71, p less than 0.001; and r = 0.70, p less than 0.001, respectively). Lymphocyte potassium concentration was not related to lymphocyte sodium or free calcium concentration in each group. In patients with essential hypertension, intracellular sodium and free calcium concentrations were negatively correlated with plasma renin activity (r = -0.66, p less than 0.001; r = -0.60, p less than 0.001, plasma norepinephrine concentration. These results suggest that a considerable relationship exists between intracellular sodium and free calcium in lymphocytes and that, in essential hypertension, the alteration in cellular metabolism of sodium and calcium may be linked to the renin system but not to blood pressure, age, or adrenergic activity.
Thromboxane and vascular smooth muscle cell growth in genetically hypertensive rats.
Authors: Ishimitsu T , Uehara Y , Ishii M , Ikeda T , Matsuoka H , Sugimoto T
Published: June 2012

The vascular wall has the capacity to produce thromboxane A2. However, the role of vascular thromboxane A2 is still uncertain. In this study, we examined the relationship between vascular thromboxane A2 generation and vascular smooth muscle cell growth in spontaneously hypertensive rats (SHR). Vascular thromboxane A2 generation was significantly enhanced by 49% in 5-week-old and by 117% in 15-week-old SHR as compared with age-matched Wistar-Kyoto rats (WKY). Thromboxane A2 generation was also significantly enhanced by 59% in the cultured vascular smooth muscle cells of SHR when compared with production in WKY. Vascular smooth muscle cells of SHR exhibited a significantly shortened doubling time (by 32%) and greater [3H]thymidine uptake (by 56%), as compared with those of WKY. OKY 046 (10(-5) M), a thromboxane synthase inhibitor, significantly tempered the rapid vascular smooth muscle cell growth in SHR by 9% for doubling time and by 10% for [3H]thymidine uptake. OKY 046 did not influence the doubling time of WKY. Conversely, a stable analogue of thromboxane A2 dose-dependently stimulated the [3H]thymidine uptake by vascular smooth muscle cells of WKY, and, at a concentration of 10(-5) M, shortened the doubling time of vascular smooth muscle cells of WKY by 11%, whereas it showed slight effects on SHR. These data indicate that vascular thromboxane A2 is involved in the regulatory mechanism of vascular smooth muscle cell growth and that enhanced vascular thromboxane A2 generation is partly responsible for the rapid proliferation of vascular smooth muscle cells of SHR. The alterations of vascular thromboxane production may be a key trait for genetic hypertension.
Adenosine in renin-dependent renovascular hypertension.
Authors: Ohnishi A , Li P , Branch R A , Biaggioni I O , Jackson E K
Published: June 2012

Our previous studies support the hypothesis that activation of the renin-angiotensin system by renal ischemia elevates adenosine levels and that adenosine acts in a negative feedback loop to limit renin release and to mitigate some of the hypertension-producing effects of angiotensin II. To further test this hypothesis, we compared the time course of caffeine-induced increases in plasma renin activity with the time course of changes in plasma levels of adenosine in two models of renin-dependent renovascular hypertension. Also, we compared the effects of caffeine on plasma renin activity and arterial blood pressure in renin-dependent versus renin-independent renovascular hypertension. In comparison to sham-operated rats, plasma levels of adenosine in the left and right renal veins and aorta were elevated severalfold in two-kidney, one clip rats (2K1C) 1 week after left renal artery clipping. However, adenosine levels declined during the second and third weeks after clipping. In 2K1C rats treated chronically with caffeine, plasma renin activity was markedly elevated during the first week after operation as compared to non-caffeine-treated 2K1C rats. However, during the second and third weeks after clipping, caffeine had lesser effects on plasma renin activity. A temporal relationship between plasma adenosine levels and caffeine-induced hyperreninemia was also observed in rats with aortic ligation. Caffeine accelerated hypertension in 2K1C rats and rats with aortic ligation (renin-dependent renovascular hypertension), but it had no effect on plasma renin activity or blood pressure in one-kidney, one clip rats (renin-independent renovascular hypertension). These results lend further support to the hypothesis that adenosine functions to mitigate the renin-angiotensin system in renin-dependent renovascular hypertension.
Arteriolar diameter and tissue oxygen tension during muscle contraction in hypertensive rats.
Authors: Boegehold M A , Bohlen H G
Published: June 2012

This study evaluated the possibility that in hypertension, mechanisms that maintain near normal arteriolar diameters at elevated arteriolar pressures limit the ability of skeletal muscle arterioles to dilate in response to an increase in tissue metabolism. The spinotrapezius muscles of 16- to 20-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were contracted at frequencies of 1, 2, 4, and 8 Hz. The inner diameters of first-order through third-order arterioles were measured at rest and following 3 minutes of contractions. Tissue oxygen tension (PO2) at the venous end of capillaries was monitored during 8-Hz contractions. At rest, following contractions, and after maximum dilation with adenosine, the inner diameters of arterioles of equivalent branch order were not significantly different in SHR and WKY. Opening of closed arterioles during muscle contraction and adenosine application occurred in less than 5% of the observations in both groups. The resting tissue PO2 was 25.5 +/- 1.3 mm Hg in normal rats and 26.1 +/- 2.1 mm Hg in SHR. At nearly maximum vasodilation during 8-Hz stimulation, tissue PO2 recovered to 81.9 +/- 12.7% of control in WKY but only to 41.2 +/- 13.0% of control in SHR. These observations indicate that the expression of local regulatory mechanisms related to tissue metabolism is virtually normal in the spinotrapezius muscle vasculature of SHR in the context of arteriolar dilation. However, at near maximum performance, factors other than absolute arteriolar diameter preclude the normal preservation of tissue PO2 in the spinotrapezius muscle of SHR.
Dietary sodium change in primary aldosteronism. Atrial natriuretic factor, hormonal, and vascular responses.
Authors: Pedrinelli R , Bruschi G , Graziadei L , Taddei S , Panarace G , Orlandini G , Natali A , Borghetti A , Salvetti A
Published: June 2012

Atrial natriuretic factor (ANF) may be physiopathologically involved in several clinical conditions including human hypertension. However, few data are available regarding this putative hormone and its relationship to aldosterone, blood pressure, and vascular responsiveness to alpha-adrenergic receptor stimulation in primary aldosteronism, a volume-expanded, low-renin model of human hypertension. For this reason, the behavior of supine and upright plasma ANF as related to aldosterone, blood pressure, and forearm alpha-adrenergic sensitivity (plethysmographic technique) to intra-arterial norepinephrine infusion was studied in eight patients with primary aldosteronism (five with adenomas, three with hyperplasia) before and at the end of two sequential 1-week low (20 mmol/day) and high sodium (200 mmol/day) diet periods. Basal, predict ANF concentrations decreased and increased after low and high sodium intakes, respectively. Furthermore, highly significant postural ANF decrements after 1 hour of standing occurred with each diet, although they were lower after the low than after the high sodium diet. Plasma aldosterone, either supine or upright, was insensitive to dietary sodium manipulations, suggesting the absence of ANF-mediated control of aldosterone secretion in our patients. In spite of about twofold higher ANF concentrations during the high than during the low sodium diet, forearm vascular sensitivity to intra-arterial norepinephrine infusion did not change during the study. Furthermore, systemic arterial blood pressure rose to a highly significant extent after dietary sodium content was increased, thus casting doubt on a role for ANF as an endogenous long-term modulator of systemic blood pressure and peripheral alpha-adrenergic sensitivity in patients with primary aldosteronism.
Erythrocyte water, Na+-K+ cotransport, and forearm vascular function in humans.
Authors: Weder A B , Egan B M
Published: June 2012

We examined the relationships between erythrocyte (RBC) composition (Na+, K+, and water content) and ouabain-insensitive transports (Na+-K+ cotransport, Li+-Na+ countertransport) and forearm vascular hemodynamics under standardized basal conditions and during vasoconstriction (intra-arterial infusion of graded doses of norepinephrine and angiotensin II) and vasodilation (intra-arterial phentolamine and postischemic exercise). RBC water content correlated positively and significantly (r = 0.53, p = 0.001) with minimum forearm vascular resistance, a measure of vascular structural change, and negatively with maximal forearm blood flow (r = -0.55, p less than 0.001). Similar correlations with forearm vascular resistance and blood flow were observed under all experimental conditions. RBC Na+-K+ cotransport correlated positively and significantly (r = 0.43, p = 0.01) with the change in forearm blood flow produced by phentolamine, a functional measure of alpha-adrenergic tone, and was as strong an independent predictor of phentolamine-induced blood flow change as was arterial norepinephrine concentration. RBC Na+-K+ cotransport was also significantly positively correlated with residual forearm blood flow and resistance after phentolamine administration, where nonadrenergic influences predominate. RBC water correlated negatively with Li+-Na+ countertransport (r = -0.33, p less than 0.05) and Na+-K+ cotransport (r = -0.44, p less than 0.01). We propose that RBC water is a marker for a vascular structural property that contributes to vascular reactivity. RBC Na+-K+ cotransport seems to relate most strongly to the sympathetically mediated control of forearm blood flow and may also be linked to the intrinsic myogenic tone of the forearm vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)
High NaCl predisposes Dahl rats to cerebral infarction after middle cerebral artery occlusion.
Authors: Coyle P
Published: June 2012

High (8%) and low (0.3%) NaCl diets were administered for 3 weeks before testing inbred Dahl salt-sensitive (SS/Jr) or salt-resistant rats (SR/Jr) for altered susceptibility to cerebral infarction after occlusion of the middle cerebral artery. At occlusion time, mean systolic blood pressure (BP) was 201 +/- 7 mm Hg in SS/Jr fed a high NaCl diet. Two weeks later an atrophied infarct was present in the territory of the occluded artery of all (n = 10) hypertensive SS/Jr, and infarct size was correlated with BP at occlusion time (p less than 0.01). In normotensive control SS/Jr fed a low NaCl diet (n = 11), BP (118 +/- 3 mm Hg), frequency of infarction (18%), and infarct size were all significantly less (p less than 0.05) than in the hypertensive rats. In SR/Jr fed a high (n = 11) or low (n = 10) NaCl diet, BP was not statistically different (112 +/- 4 vs 116 +/- 4 mm Hg). Cerebral infarction frequency was significantly (p less than 0.05) greater in SR/Jr fed a high NaCl diet (73%) than in SR/Jr receiving a low NaCl diet (20%), but infarct size was not correlated with BP in SR/Jr (p greater than 0.05). Thus, elevated NaCl intake in SS/Jr and SR/Jr before middle cerebral artery occlusion predisposes to cerebral infarction, but differences in infarct size and its correlation with BP suggest the controlling factors are not identical in the two strains.
Central attenuation of aortic baroreceptor reflex in prehypertensive DOCA-salt-loaded rats.
Authors: Nakamura Y , Takeda K , Nakata T , Hayashi J , Kawasaki S , Lee L C , Sasaki S , Nakagawa M , Ijichi H
Published: June 2012

To determine whether the arterial baroreceptor reflex can act to oppose the development of hypertension, deoxycorticosterone acetate (DOCA)-salt hypertension was produced in sinoaortic-denervated and sham-operated rats. Systolic blood pressure measured by tail cuff started to increase in both sinoaortic-denervated and sham-operated rats 7 days after DOCA treatment, and the hypertension developed identically in both denervated and sham-operated rats. These findings suggest that the baroreceptor reflex cannot act against the development of hypertension. To determine whether the baroreceptor reflex is attenuated before the development of hypertension, bradycardiac and sympathoinhibitory responses to i.v. injections of norepinephrine were examined. Bradycardic and sympathoinhibitory responses were significantly smaller in DOCA-salt-treated rats in both prehypertensive (5th day after DOCA-salt treatment) and hypertensive stages (21st day after treatment). In urethane-anesthetized DOCA-loaded and control rats on the 5th day after treatment, aortic depressor nerve stimulation elicited frequency-dependent depressor and bradycardic responses accompanied by inhibition of sympathetic nerve activity in both DOCA-loaded and control rats. However, those responses were significantly smaller in DOCA-loaded rats than in control rats. These results suggest that the central component of the baroreceptor reflex mediated by the aortic depressor nerve is impaired before hypertension develops and that this impairment may contribute to the development of hypertension in DOCA-salt-treated rats.
Central modulation of baroreceptor reflex response to phenylephrine by dihydropyridines in rats.
Authors: Lacolley P , Laurent S , Tsoucaris-Kupfer D , Legrand M , Brisac A M , Schmitt H
Published: June 2012

The effects of two dihydropyridine derivatives, the calcium channel agonist BAY k 8644 or the antagonist PN 200-110, on the central nervous components of the baroreceptor reflex control of heart rate during activation of baroreceptors by phenylephrine (2 micrograms i.v.) were studied in pentobarbital-anesthetized normotensive (Wistar) rats and spontaneously hypertensive rats (SHR). To rule out an effect on peripheral vessels or on the sinoauricular node (or on both), BAY k 8644 and PN 200-110 were administered intracerebroventricularly (i.c.v.) at doses that did not change blood pressure. Baroreceptor reflex sensitivity was calculated as the slope of the relationship between systolic arterial pressure and heart period. Baroreceptor reflex sensitivity increased with time following the onset of anesthesia. In SHR, injection of BAY k 8644 (3 micrograms/kg i.c.v.) suppressed the time-dependent increase in baroreceptor reflex sensitivity. The inhibitory effect of BAY k 8644 (3 micrograms/kg i.c.v.) on the time-dependent increase in baroreceptor reflex sensitivity was suppressed by pretreatment with PN 200-110 (0.6 microgram/kg i.c.v.) but not with the solvent, indicating that the central effect of BAY k 8644 occurred at the level of specific dihydropyridine binding sites. In addition, the inhibitory effect of BAY k 8644 (3 micrograms/kg i.c.v.) on the time-dependent increase in baroreceptor reflex sensitivity was suppressed by pretreatment with the muscarinic antagonist atropine methylnitrate (80 micrograms/kg i.c.v.) but not with the solvent. In normotensive rats, the time-dependent increase in baroreceptor reflex sensitivity was not significantly altered by BAY k 8644 (3 micrograms/kg i.c.v.).(ABSTRACT TRUNCATED AT 250 WORDS)
Fate of recombinant human renin administered exogenously to anesthetized monkeys.
Authors: Hiruma M , Kim S , Ikemoto F , Murakami K , Yamamoto K
Published: June 2012

Highly purified recombinant human renin (rh-renin), synthesized by Chinese hamster ovary cells, was labeled with iodine-125 and was given intravenously to pentobarbital-anesthetized common marmosets (Callithrix jacchus) to study the fate of the circulating renin. Specific anti-rh-renin antiserum was used to identify the 125I-rh-renin. Plasma disappearance of the exogenously administered 125I-rh-renin in marmosets (n = 6) showed two exponential components, with a half-life of 12.1 +/- 1.9 minutes for the rapid component and 120.3 +/- 16.4 minutes for the slow component. The metabolic clearance rate was 1.17 +/- 0.26 ml/min/kg. Thirty minutes after the injection of 125I-rh-renin, 43.1 +/- 0.9 and 3.5 +/- 0.5% of the injected dose had distributed to the liver and the kidneys, respectively. With time, the accumulated 125I-rh-renin in the liver and kidneys decreased. The accumulation of 125I-rh-renin was less than 1% of the dose injected in other organs such as lungs, heart, spleen, adrenal glands, testes, and ovaries. Analysis of liver and kidney extracts by high performance liquid chromatography at 30 and 120 minutes indicated that immunoreactive 125I-rh-renin decreased with time and was accompanied by an increase in nonimmunoreactive degradation products of a low molecular weight. The incubation of 125I-rh-renin with monkey or human plasma at 37 degrees C did not degrade the labeled renin. Therefore, rh-renin was rapidly cleared from the circulation by the liver and the kidney.
Regulation of renin gene expression in hypertensive rats.
Authors: Makrides S C , Mulinari R , Zannis V I , Gavras H
Published: June 2012

A carboxy terminal renin complementary DNA (cDNA) clone from rat kidney was isolated, characterized, and used as a probe for renin messenger RNA (mRNA) quantification in normotensive and hypertensive rats. RNA blotting analysis detected renin mRNA in control kidney and brain. Deoxycorticosterone acetate (DOCA) and high salt (1%) treatment of experimental animals resulted in a greater than 95% decrease in the content of renin mRNA in the kidney, as compared with values in control rats receiving 0.4% NaCl in their diet. In contrast, high salt (1%) treatment alone caused only a twofold decrease in kidney renin mRNA content, as compared with values in controls. DOCA and low salt (0.04%) or low salt (0.04%) treatment alone caused a 1.5-fold increase in the kidney renin mRNA content, as compared with values in control rats. These results indicate that DOCA and salt have a synergistic effect in depressing renin mRNA levels in kidney. Clipping of the left renal artery caused a threefold increase in the steady state level of renin mRNA in the ischemic kidney and a 0.5-fold decrease in the hypertrophied kidney. The data are consistent with the hypothesis that blood pressure and other stimuli regulate the expression of the renin gene in vivo.