bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum calcium fractions in essential hypertensive and matched normotensive subjects.
Authors: Folsom A R , Smith C L , Prineas R J , Grimm R H
Published: June 2012

Concentrations of serum total calcium and serum calcium fractions were compared between 28 hypertensive subjects and 28 race-sex-age-matched normotensive controls. Mean levels of serum total calcium were not different between the two groups. Hypertensive subjects had lower mean serum levels of ultrafilterable calcium (-0.32 mg/dl; p = 0.01), ionized calcium (-0.07 mg/dl; p = 0.09), and complexed calcium (-0.23 mg/dl; p = 0.04) and higher levels of protein-bound calcium (+0.36 mg/dl; p = 0.07). Estimated dietary calcium intake was similar in the two groups. These findings add to the evidence that essential hypertension is associated with perturbations in calcium metabolism.
Effects of propranolol on the impulse activity of cardiovascular sympathetic afferent fibers.
Authors: Lombardi F , Casalone C , Malfatto G , Gnecchi Ruscone T , Casati R , Malliani A
Published: June 2012

The influence of beta-adrenergic receptor blockade on the impulse activity of 21 cardiovascular sympathetic afferent nerve fibers (11 from the thoracic aorta, 10 from the pulmonary veins), isolated from the left sympathetic rami communicantes T-3 and T-4 was studied in anesthetized, vagotomized cats. Aortic pressure, heart rate, and neural discharge were recorded during control conditions and during brief aortic occlusions of comparable amplitude and duration. Administration of dl-propranolol (0.2-0-4 mg/kg) did not modify aortic pressure or neural discharge of the fibers during control conditions, although, as expected, heart rate was diminished. dl-Propranolol administration did change the response of cardiovascular sympathetic afferents to similar aortic pressure increases. Before drug administration, aortic occlusion caused a significant increase in neural discharge of both aortic and pulmonary vein sympathetic afferent fibers, from 0.52 +/- 0.12 to 1.64 +/- 0.31 and from 0.67 +/- 0.10 to 2.08 +/- 0.25 impulses/sec, respectively (p less than 0.05). After dl-propranolol administration, comparable increases in aortic pressure resulted in slight but not significant increases in neural discharge of aortic and pulmonary vein fibers. Administration of d-propranolol (0.4-0.6 mg/kg), which possesses only membrane-stabilizing properties, did not modify the firing rate of four pulmonary sympathetic afferents, which subsequently decreased their response to pressure rises after administration of dl-propranolol. These results indicate that beta-adrenergic receptor blockade reduces the responsiveness to hemodynamic stimuli of sympathetic cardiovascular afferent fibers that are capable of mediating excitatory pressor reflexes.
Hemodynamic effects of infusion versus bolus administration of atrial natriuretic factor.
Authors: Lappe R W , Todt J A , Wendt R L
Published: June 2012

The cardiovascular responses to intravenous bolus administration of several synthetic atrial natriuretic peptides were examined in conscious spontaneously hypertensive rats and compared with the hemodynamic effects of continuous infusions of the peptides. Rats were instrumented with pulsed Doppler flow probes to allow measurement of regional blood flow in the conscious, unrestrained hypertensive rat. Bolus administration of increasing doses (0.036-18 nmol/kg) of atriopeptin II, alpha-rat atrial natriuretic peptide, Wy-47,663, or alpha-human atrial natriuretic peptide caused short-lived, dose-dependent reductions in mean arterial pressure and renal vascular resistance. A marked but transient (10-40 seconds) increase in renal blood flow was observed after administration of the peptides. Mesenteric and hindquarter vasodilation also were observed after bolus injection of high doses of the atrial peptides. Infusion of alpha-rat atrial natriuretic peptide or Wy-47,663 (0.045-1.44 nmol/kg/min) resulted in sustained reductions in mean arterial pressure. The fall in arterial pressure was accompanied by significant reductions in regional blood flow in the renal, mesenteric, and hindquarter vascular beds. Dose-dependent increases in regional vascular resistances were observed in all three vascular beds during the peptide infusions. These data indicate that the hemodynamic responses to synthetic atrial peptides are greatly dependent on the mode of administration of the peptide in conscious spontaneously hypertensive rats. Stable, sustained responses were observed only during infusion steady state conditions.
In vitro secretion of immunoreactive tonin from dispersed rat submandibular gland cells.
Authors: Hirata Y , Tomita M , Fujita T , Ikeda M
Published: June 2012

Dispersed cells from the submandibular gland of the male rat were prepared by collagenase treatment to study the mechanism by which immunoreactive tonin is secreted in vitro. Norepinephrine, epinephrine, and phenylephrine stimulated tonin release, an effect that was inhibited by phentolamine but not by propranolol, whereas isoproterenol, carbachol, histamine, and serotonin did not stimulate tonin release. The stimulatory effect elicited by alpha-adrenergic agonists was inhibited by both removal of Ca2+ from the medium and addition of diltiazem and nifedipine, both selective calcium channel blockers. The divalent cation ionophore A23187 stimulated tonin release in the presence of Ca2+, but not in the presence of Mg2+. Dibutyryl cyclic adenosine 3',5'-monophosphate, methylisobutylxanthine, angiotensin II, and vasoactive intestinal peptide had no effect on tonin release. The apparent molecular size of immunoreactive tonin released into the medium under basal and norepinephrine-stimulated conditions was similar to that of standard tonin by gel exclusion chromatography. These data suggest that the in vitro secretion of immunoreactive tonin from rat submandibular gland is initiated by activation of alpha-adrenergic receptors and apparently involves a mechanism dependent not on cyclic adenosine 3',5'-monophosphate, but on the influx of extracellular Ca2+.
Role of dopamine in the inhibition of vasopressin secretion by L-dopa in carbidopa-treated dogs.
Authors: Reid I A , Chou L , Chang D , Keil L C
Published: June 2012

Elevation of brain catecholamine levels by systemic administration of L-dopa in dogs pretreated with the dopa decarboxylase inhibitor carbidopa inhibits the secretion of vasopressin and adrenocorticotropic hormone (ACTH) and decreases arterial blood pressure. The aim of the present study was to determine whether the inhibition of vasopressin secretion is mediated by dopamine or norepinephrine, both of which have been implicated in the control of vasopressin secretion, and whether the decrease in vasopressin secretion contributes to the suppression of ACTH secretion and fall in blood pressure produced by L-dopa. This was accomplished by comparing the effects of dopamine and alpha-adrenergic receptor antagonists on vasopressin, ACTH, and blood pressure responses to L-dopa. The effect of a specific antagonist of the vasoconstrictor action of vasopressin also was studied. Injection of L-dopa (20 mg/kg i.v.) in dogs pretreated with carbidopa (20 mg/kg i.v.) caused reductions in plasma vasopressin concentration (from 16.0 +/- 4.8 to 3.8 +/- 0.9 pg/ml; p less than 0.05), plasma ACTH concentration (from 96.0 +/- 20.4 to 49.2 +/- 10.0 pg/ml; p less than 0.05), and mean arterial pressure (from 121 +/- 6 to 78 +/- 5 mm Hg; p less than 0.05). Pretreatment with pimozide (1 mg/kg i.p.) completely blocked the inhibition of vasopressin secretion by L-dopa but failed to block the suppression of ACTH secretion (57.6 +/- 11.8 to 34.0 +/- 5.1 pg/ml; p less than 0.05) or the decrease in mean arterial pressure (126 +/- 5 to 93 +/- 7 mm Hg; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Modulation of guanylate cyclase by lipoxygenase inhibitors.
Authors: Clark D L , Linden J
Published: June 2012

Drugs that inhibit endothelium-dependent relaxation were tested to determine their effect on soluble guanylate cyclase purified from dog aorta. Basal, arachidonic acid (10(-5) M)-stimulated, and nitroprusside (5 X 10(-5) M)-stimulated guanylate cyclase activities were inhibited by methylene blue and the lipoxygenase inhibitors nordihydroguaiaretic acid and eicosatetraynoic acid. The effective inhibitory doses were in the range of those that have been reported to inhibit endothelium-dependent relaxation. Other compounds known to inhibit endothelium-dependent relaxation had little or no effect on guanylate cyclase activity. Basal guanylate cyclase activity was more resistant to inhibition than were activated states of the enzyme. The data suggest that reported inhibition of endothelium-dependent relaxation by some lipoxygenase inhibitors may be the result, at least in part, of their direct effect on guanylate cyclase activity.
Salt level in weaning diet affects saline preference and fluid intake in Dahl rats.
Authors: Ferrell F , Lanou A , Gray S D
Published: June 2012

Weanling Dahl salt-sensitive (DS) and salt-resistant (DR) rats were used to compare effects of feeding high or low NaCl diets on taste preference for, and intake of, a wide range of saline concentrations. The DS and DR were fed either 8.0 or 0.4% dietary NaCl for 4 weeks. Then, with all animals fed the 0.4% NaCl diet, their taste preferences for 0.0001 to 0.56 M saline were assessed using three 24-hour two-bottle preference tests of each solution versus distilled deionized water. Saline preference and intake were influenced by concentration and its interaction with genotype, with DS exhibiting higher preferences than DR for hypotonic saline. The DS preexposed to 8.0% dietary NaCl showed elevated consumption levels of water and total fluid (saline + water) that persisted throughout the 5-week test period, despite transfer to the 0.4% NaCl diet before the initiation of preference testing. Findings indicate that genotype, dietary NaCl levels in weaning diet, and saline concentration of preference test solutions interact to influence saline preference and saline and water intake in Dahl rats.
Sodium pump activity and calcium relaxation in vascular smooth muscle of deoxycorticosterone acetate-salt rats.
Authors: Soltis E E , Field F P
Published: June 2012

The Na+-K+ pump activity was determined in femoral arterial smooth muscle from deoxycorticosterone acetate (DOCA)-salt hypertensive rats using potassium relaxation and ouabain-sensitive 86Rb uptake as indices. The membrane-stabilizing effect of calcium and its relation to Na+-K+ pump activity also were examined. Femoral arteries from DOCA-salt rats exhibited a greater relaxation in response to potassium addition after contraction with norepinephrine in a low potassium (0.6 mM) Krebs solution. The concentration of potassium required to produce a 50% relaxation was significantly less in DOCA-salt rats. Ouabain-sensitive 86Rb uptake was significantly greater at 3, 10, and 20 minutes of 86Rb incubation in femoral arteries from DOCA-salt rats. Linear regression analysis revealed a significant correlation between the uptake of 86Rb and time of incubation in both control and DOCA-salt rats. A significant difference in the slopes of the regression lines showed that the rate of uptake was greater in DOCA-salt rats. No difference was observed in ouabain-insensitive 86Rb uptake. A dose-dependent relaxation in response to increasing concentrations of calcium following contraction to norepinephrine was observed in femoral arteries from control and DOCA-salt rats. The relaxation was directly dependent on the level of extracellular potassium and was blocked by ouabain. Femoral arteries from DOCA-salt rats relaxed to a significantly greater extent in response to calcium at each level of potassium when compared with controls. These results provide further evidence for an increase in Na+-K+ pump activity in vascular smooth muscle from DOCA-salt hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Age-related changes in blood pressure.
Authors: Landahl S , Bengtsson C , Sigurdsson J A , Svanborg A , Svärdsudd K
Published: June 2012

This report is based on three different representative population samples of a total of 1304 men (50-79 years old) and 1246 women (38-79 years old) observed for up to 12 years. Subjects' consumption of antihypertensive drugs and blood pressure levels in subjects with and without such treatment are presented. The prevalence of treatment with antihypertensive drugs (including beta-blockers and diuretics for other indications) increased from 2% at age 50 years to 37% at 79 years of age among the men and from 1% at 38 years to 61% at 79 years of age among the women. The mean systolic/diastolic blood pressure in untreated subjects increased from 138/91 mm Hg at age 50 years to 159/91 mm Hg at age 70 years in the men and from 123/79 mm Hg at age 38 years to 168/93 mm Hg at age 70 years in the women. At age 79 years the mean systolic/diastolic blood pressure was 155/83 mm Hg in the men and 161/85 mm Hg in the women. In a longitudinal follow-up of reexamined subjects, there was an increase in systolic blood pressure levels up to age 75 years and a reduction in diastolic blood pressure after age 75 years in both sexes.
An orally active inhibitor of renin.
Authors: Pals D T , Thaisrivongs S , Lawson J A , Kati W M , Turner S R , DeGraaf G L , Harris D W , Johnson G A
Published: June 2012

A potent renin inhibitor, U-71038 (Boc-Pro-Phe-N-MeHis-Leu psi[CHOHCH2]Val-Ile-Amp), was tested for oral effectiveness. Enzyme kinetic studies indicated that U-71038 was a competitive inhibitor of hog renin with an inhibitor constant (Ki) value of 12 nM. Intravenous as well as oral administration of U-71038 to anesthetized, ganglion-blocked rats infused with hog renin elicited dose-related hypotensive responses. Intravenous administration of U-71038 to conscious, sodium-depleted monkeys caused dose-related decreases of blood pressure and plasma renin activity without affecting heart rate. Similarly, the oral administration of U-71038 at 50 mg/kg to conscious, sodium-depleted monkeys elicited a pronounced hypotension and decrease in plasma renin activity that persisted for 5 hours. The hypotensive responses elicited by intravenous and oral administration of U-71038 to hog renin-infused rats and sodium-depleted monkeys were shown to be due entirely to inhibition of the renin-angiotensin system. A comparison of the results obtained after the intravenous administration of U-71038 with the results obtained after the oral administration of U-71038 implied that at least 10% of the orally administered U-71038 must have been absorbed to cause the observed effects in hog renin-infused rats and sodium-depleted monkeys. The studies demonstrated that an inhibitor of renin with a long duration of action and with oral effectiveness is a feasible entity.
Effects of angiotensin inhibition and renal denervation in two-kidney, one clip hypertensive rats.
Authors: Rademacher R , Berecek K H , Ploth D W
Published: June 2012

Neural and angiotensin-mediated influences that alter hemodynamic and excretory behavior of the nonclipped kidney of two-kidney, one clip hypertensive rats were assessed by sequential acute surgical denervation of the nonclipped kidney and intravenous infusion of converting enzyme inhibitor (SQ 20881), 3 mg/kg X hr. Normal and two-kidney, one clip hypertensive rats (0.2-mm silver clip on the right renal artery 3-4 weeks before study) were prepared to allow study of each kidney. Mean arterial blood pressure of two-kidney, one clip hypertensive rats fell significantly from control values of 149 +/- 6 to 135 +/- 6 mm Hg after denervation of the nonclipped kidney. Despite this decrease in arterial pressure, the nonclipped kidney exhibited significant increases in glomerular filtration rate (from 1.00 +/- 0.08 to 1.24 +/- 0.08 ml/min), sodium excretion (from 88 +/- 39 to 777 +/- 207 nEq/min), fractional sodium excretion (from 0.06 +/- 0.02 to 0.54 +/- 0.14%), and urine flow rate (from 3.7 +/- 0.5 to 8.2 +/- 1.1 microliter/min). A significant decrease in glomerular filtration rate (from 1.12 +/- 0.07 to 0.85 +/- 0.08 ml/min) with no change in excretory function was observed for the clipped kidney following denervation of the nonclipped kidney. Intravenous addition of converting enzyme inhibitor significantly increased renal blood flow (from 7.0 +/- 1.3 to 10.6 +/- 1.5 ml/min) and sodium excretion (from 777 +/- 207 to 1384 +/- 425 nEq/min) for the nonclipped kidney; blood pressure decreased from 135 +/- 6 to 123 +/- 4 mm Hg, and renal vascular resistance decreased significantly (from 22 +/- 3 to 13 +/- 2 mm Hg X min/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Antihypertensive drugs inhibit hypertension-associated aortic DNA synthesis in the rat.
Authors: Loeb A L , Bean B L
Published: June 2012

The effect of antihypertensive drug treatment on aortic DNA synthesis was examined in rats with two-kidney, one clip renal hypertension and in spontaneously hypertensive rats (SHR). In two-kidney, one clip hypertensive rats, hypertension developed over a 2-week period. Four days after clipping the renal artery, during the onset of hypertension, there was an increase in aortic DNA synthesis. Aortic DNA synthesis was also increased 3 weeks later, when hypertension had been established. Captopril, hydralazine, and verapamil were each able to prevent the increase in aortic DNA synthesis and the rise in blood pressure when given throughout the first 5 days of the developing phase of hypertension, or when given to rats with established hypertension. Drug treatment of sham-operated rats had no significant effect on DNA synthesis, although blood pressure was decreased. There were no differences in blood pressure or aortic DNA synthesis in 4-week-old SHR, as compared with age-matched Wistar-Kyoto (WKY) controls or normal Wistar rats. At 17 weeks of age, when hypertension was established, aortic DNA synthesis was significantly enhanced in the SHR. Captopril or hydralazine treatment was able to reduce blood pressure and DNA synthesis to levels seen in the WKY. At 21 weeks of age, DNA synthesis in the SHR had declined to the same levels as in the WKY. Captopril, hydralazine, and verapamil may have a common ability to reduce intracellular calcium and therefore inhibit DNA synthesis. In support of this, ouabain treatment, which increases intracellular calcium by inhibiting the Na+-K+ pump, produced a significant increase in the rate of DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of 1-hour and 24-hour blood pressure recordings in central or peripheral baroreceptor-denervated rats.
Authors: Buchholz R A , Hubbard J W , Nathan M A
Published: June 2012

We compared the mean arterial pressure and heart rate activity of conscious, unrestrained rats during 1-hour and 24-hour continuous recording sessions, 3 to 4 weeks after either sinoartic denervation, placement of electrolytic lesions in the nucleus tractus solitarii, or sham operations. Sinoaortic denervation and nucleus tractus solitarii lesions both eliminated the reflex bradycardia to a phenylephrine-induced pressor response. No difference was found in the average level and lability of the mean arterial pressure between 1-hour and 24-hour recordings for any group. No elevation in the average mean arterial pressure of rats with nucleus tractus solitarii lesions was observed, although a mild hypertension was noted in half the sinoarotic-denervated rats, while the other half were normotensive. Group differences were not found for heart rate or heart rate variability; however, 24-hour recordings yielded significantly higher values than 1-hour recordings for all groups. Both medullary lesions and sinoaortic denervation significantly increased the lability of the mean arterial pressure, but the magnitude of the increase was significantly greater in the rats with lesions. The lability of the mean arterial pressure in sinoaortic-denervated rats depended largely on movement-related depressor responses that produced a negative skew in the frequency distribution of their mean arterial pressure. Rats with nucleus tractus solitarii lesions exhibited both pressor and depressor responses that resulted in pressure distributions that had a slight positive skew similar to that displayed by control rats. It is concluded that short-term continuous recordings of mean arterial pressure and heart rate accurately estimate the altered cardiovascular activity of baroreceptor-denervated rats. The differences in the cardiovascular responses of central and peripheral baroreceptor-denervated rats are believed to be due to the more extensive destruction by nucleus tractus solitarii lesions of central neurons and pathways involved in cardiovascular regulation.
Isomyosin transitions in ventricles of aldosterone-salt hypertensive rats.
Authors: Martin A F , Paul R J , McMahon E G
Published: June 2012

The isomyosin composition in left and right ventricles from aldosterone-salt-treated hypertensive rats and from vehicle-infused and aldosterone-infused normotensive control rats was compared. A significant incremental increase (20%) in the percentage of V3 isomyosin and parallel decrease in the percentage of V1 isomyosin occurred in both left and right ventricles from aldosterone-salt-treated animals compared with those in normotensive vehicle-infused controls. No change in the ventricular isomyosin distribution was observed in animals infused with aldosterone without salt, which indicates that aldosterone does not directly affect the ventricular isomyosin composition. The changes in left ventricular isomyosin composition were accompanied by significant left ventricular hypertrophy (38%; p less than 0.05), whereas no hypertrophy was observed in the right ventricle. Plasma thyroxine levels were significantly lower in aldosterone-salt-treated rats (3.7 +/- 0.6 micrograms/dl; p less than 0.05) than in normotensive vehicle-infused (6.0 +/- 0.7 micrograms/dl) or aldosterone-infused (6.7 +/- 0.3 micrograms/dl) controls. These results indicate that factors such as alterations in thyroid status or a volume overload component of this hypertensive model, in addition to increased systolic blood pressure, may contribute to a biventricular shift in isomyosin composition in the aldosterone-salt model of hypertension.
Central adrenergic receptor control of renal function in conscious hypertensive rats.
Authors: Koepke J P , DiBona G F
Published: June 2012

The role of central nervous system alpha-adrenergic and beta-adrenergic receptors in the increased renal sympathetic nerve activity and antinatriuresis resulting from environmental stress (air stress) in conscious spontaneously hypertensive rats (SHR) was examined. Intracerebroventricular administration of the alpha 2-adrenergic receptor agonist clonidine (1, 5, and 15 micrograms) prevented the effects of air stress on renal sympathetic nerve activity and urinary sodium excretion. Clonidine, 5 and 15 micrograms, lowered baseline mean arterial pressure and renal sympathetic nerve activity and increased baseline urine flow rate and urinary sodium excretion; clonidine, 1 micrograms, had no effect on these baseline levels. Intravenous administration of 5 micrograms, but not 1 microgram of clonidine, abolished the renal responses to air stress. Intracerebroventricular administration of alpha 2-adrenergic receptor antagonists (yohimbine, rauwolscine) reversed the effects of clonidine, alpha 2-adrenergic receptor blockade alone, alpha 1-adrenergic receptor blockade (20 micrograms prazosin), or combined alpha 1-adrenergic and alpha 2-adrenergic receptor blockade (30 micrograms phenoxybenzamine) had no effect on the renal sympathetic nerve activity or antinatriuretic responses to air stress. Intracerebroventricular, but not intravenous, administration of the beta 2-adrenergic receptor antagonist ICI 118551 (30 micrograms) prevented the increased renal sympathetic nerve activity and antinatriuretic responses to air stress. In contrast, intracerebroventricular administration of the beta 1-adrenergic receptor antagonist atenolol (30 micrograms) had no effect on the renal responses to air stress. These results indicate that the increased renal sympathetic nerve activity and antinatriuresis resulting from environmental stress in conscious SHR can be prevented by pharmacological stimulation of central alpha 2-adrenergic receptors or by blockade of central beta 2-adrenergic receptors.
Dopaminergic binding and inhibitory effect in the bovine adrenal zona glomerulosa.
Authors: Stern N , Tuck M , Ozaki L , Krall J F
Published: June 2012

Dopaminergic mechanisms may be involved in the regulation of aldosterone secretion in humans and in the rat. Whether these effects are indirect or are exerted directly at the adrenal level has not yet been resolved. We now report the identification of dopaminergic binding sites in the bovine adrenal zone glomerulosa using [3H]spiperone, a butyrophenone with high affinity for D2 dopamine receptors. Specific [3H]spiperone binding (defined as binding displaceable by 10 microns (+)-butaclamol) reached equilibrium within 20 minutes at 22 degrees C, was reversible, and was heat labile (60 degrees C). Binding was of high affinity and saturable with a Kd of 1.8 +/- 0.2 nM and maximal specific binding of 38 +/- 8 fmol/mg (means +/- SEM; n = 18). [3H]Spiperone binding was unaffected by coincubation with angiotensin II, adrenocorticotropic hormone, or KCl. Binding characteristics, including a dissociation constant at the nanomolar range, greater potency of the D2-agonist LY 171555 relative to the D1-agonist SKF 38393 in inhibiting [3H]spiperone binding, and lack of stimulation of cyclic adenosine 3',5'-monophosphate by dopamine (10(-4) M), were consistent with a predominantly D2-receptor. In vitro studies with collagenase-dispersed adrenal zona glomerulosa cells showed that dopamine (10(-4) M) attenuated angiotensin II-stimulated aldosterone secretion. These observations are consistent with a direct inhibitory effect of dopamine on aldosterone secretion in the adrenal zona glomerulosa.
Effect of weight loss on blood pressure and drug consumption in normal weight patients.
Authors: Imai Y , Sato K , Abe K , Sasaki S , Nihei M , Yoshinaga K , Sekino H
Published: June 2012

The effect of weight loss on blood pressure and on antihypertensive drug consumption was examined in 81 nonobese subjects with essential hypertension who had been chronically treated with antihypertensive drugs. A hypocaloric diet was prescribed for 5 months. A weight loss greater than 2 kg in 5 months was considered significant. Quality and quantity of antihypertensive medications were scored according to a formula. In the subjects whose medication and weight did not change, mean arterial pressure remained unchanged, whereas it decreased significantly (-7.1 +/- 1.9 mm Hg) in those who showed significant weight loss (-3.28 +/- 0.34 kg) with no change in medication. Among the subjects whose antihypertensive medication remained constant during the diet program there was a significant correlation between the change in weight and mean arterial pressure (r = 0.45, p less than 0.01). Mean arterial pressure increased significantly (+5.1 +/- 1.7 mm Hg) in subjects whose weight remained unchanged with a decrease in medication, whereas it remained significantly lower than the control (by -3.1 +/- 2.0 mm Hg) in those whose weight decreased significantly (-4.57 +/- 0.69 kg) with the decrease in medication. The weight loss-induced decrease in blood pressure occurred independently of the initial degree of obesity and the initial level of mean arterial pressure. Urinary sodium excretion in the control period and at the end of the diet program did not differ significantly between subgroups. These results indicate that, even in subjects of normal weight with essential hypertension, weight loss can induce a fall in blood pressure that leads to a reduction of antihypertensive medication.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of urapidil, clonidine, and prazosin on sympathetic tone in conscious rats.
Authors: Luft F C , Veelken R , Becker H , Ganten D , Lang R E , Unger T
Published: June 2012

To test the hypothesis that the hypotensive action of urapidil is in part related to a direct action on the brain, the central (intracerebroventricular) and peripheral (intravenous) effects of urapidil were studied and compared with those obtained with clonidine and prazosin. All studies were conducted in conscious, chronically instrumented stroke-prone spontaneously hypertensive rats (SHRSP). Efferent sympathetic nervous system activity was estimated by means of a bipolar electrode implanted on the splanchnic nerve. Only clonidine, administered intracerebroventricularly and intravenously, decreased sympathetic nerve activity. Urapidil and prazosin either did not affect sympathetic nerve activity after central administration or increased it after peripheral administration at low and high doses, respectively. Centrally administered urapidil and prazosin lowered blood pressure but also blocked the response to intravenously administered phenylephrine; this result suggests a peripheral effect. Centrally administered urapidil decreased heart rate. Urapidil given either intracerebroventricularly or into the cisterna magna had no influence on baroreceptor responses. Intravenous infusions of urapidil and prazosin in sufficient doses to lower blood pressure in spontaneously hypertensive rats by 50 mm Hg completely blocked the actions of phenylephrine. These data suggest that in conscious SHRSP urapidil lowers blood pressure through peripheral blockade of alpha 1-adrenergic receptors rather than by means of central sympathetic suppression. In this regard urapidil resembles prazosin rather than clonidine; however, the effect of urapidil on heart rate is consistent with a central mode of action.
Dopamine selectively inhibits aldosterone responses to angiotensin II in humans.
Authors: Carey R M , Drake C R
Published: June 2012

Previous studies have suggested that dopamine may have an important role as an inhibitor of aldosterone secretion in humans. Recent studies have also suggested that the adrenergic nervous system may have an important role in controlling aldosterone secretion. The present study investigated the effects of dopamine on aldosterone secretion in response to angiotensin II, with and without pretreatment with propranolol, and to adrenocorticotropic hormone, another known stimulator of aldosterone secretion. Nine normal subjects in balance at 10 mEq sodium intake received dopamine (4 micrograms/kg/min) or vehicle for 270 minutes on 2 consecutive days on three separate occasions. After 120 minutes of dopamine infusion, the subjects received a 30-minute intravenous infusion of angiotensin II (in cumulative doses of 0.5, 1, 2, 4, and 6 pmol/kg/min), angiotensin II after oral pretreatment with propranolol, or adrenocorticotropic hormone (in cumulative doses of 0.5, 1, 2, and 5 U/hr). Aldosterone responses to 2, 4, and 6 pmol/kg/min of angiotensin II (without propranolol) were greater in vehicle-treated than in dopamine-treated subjects (p less than 0.05), as was the slope of the angiotensin II-vehicle dose-response curve (0.46, p less than 0.05). Propranolol suppressed the aldosterone response to angiotensin II, but dopamine still inhibited the response. Aldosterone and cortisol secretion were stimulated equally by adrenocorticotropic hormone in dopamine-treated and vehicle-treated groups. These results suggest that dopamine selectively inhibits the aldosterone response to angiotensin II and that this response is not mediated by teh activity of dopamine at beta-adrenergic receptors.
Increased plasma vasopressin in low renin essential hypertension.
Authors: Os I , Kjeldsen S E , Skjøtø J , Westheim A , Lande K , Aakesson I , Frederichsen P , Leren P , Hjermann I , Eide I K
Published: June 2012

Baseline plasma vasopressin concentrations were measured in 48 men (all 50 years old) with decreased plasma renin concentration and untreated, sustained essential hypertension and in 29 healthy normotensive men. Mean hypertensive plasma vasopressin concentration was more than twice as high as the corresponding normotensive level (15.7 +/- 2.2 [SE] vs 7.5 +/- 1.0 pg/ml; p less than 0.001). Plasma renin concentration in the hypertensive group was reduced compared with that in the normotensive group (0.28 +/- 0.04 vs 0.46 +/- 0.06 Goldblatt units X 10(-4)/ml). These differences appeared despite virtually identical serum osmolality, creatinine clearance, and urinary sodium excretion in the two groups. In the first 38 hypertensive subjects, arterial plasma epinephrine concentrations were significantly increased over those of the first 28 control subjects (99 +/- 12 vs 68 +/- 6 pg/ml; p less than 0.025). In contrast to those with low renin essential hypertension, 35 men with normal renin essential hypertension (all 40 years old) had normal plasma vasopressin levels that were not significantly different from those in a comparable normotensive control group (3.7 +/- 0.8 vs 3.5 +/- 0.4 pg/ml). Arterial epinephrine concentrations were not significantly different between normal renin subjects and the control group. After 6 weeks of treatment with the nonselective beta-adrenergic receptor blocker oxprenolol in 11 subjects with low renin hypertension, blood pressure was reduced and the plasma vasopressin concentration fell from 27.6 +/- 6.4 to 13.5 +/- 4.2 pg/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Partitioning of erythrocytes from spontaneously hypertensive and Wistar-Kyoto rats.
Authors: Walter H , Levin E R , Krob E J , Mills S D
Published: June 2012

The charge-associated and non-charge-associated (probably lipid-related) surface properties of erythrocytes from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), from which SHR were originally derived, were studied by cell partitioning in dextran-polyethylene glycol aqueous phase systems. A major difference was found in the surface charge-associated and lipid-related properties of red blood cells from SHR and WKY: the cells from WKY had the higher partition ratio in both charge-sensitive and non-charge-sensitive phases. No difference in partitioning could be found between any two SHR nor between any two WKY. The SHR and WKY erythrocytes showed the same difference when compared with one another even when rats had the same blood pressure. When red blood cells from SHR with different blood pressure were compared, there still was no difference in their surface properties. These results suggest that the differences in both charge-associated and lipid-related surface properties of erythrocytes from SHR and WKY are strain-specific (i.e., genetic) but that there is no correlation, reflected by partitioning, between red blood cell surface properties and the degree of the rats' hypertension.
Decreased water and potassium content in erythrocytes in essential hypertension.
Authors: Kawarabayashi T , Kanayama Y , Takeuchi K , Oku H , Kohno M , Yoshimura T , Yasunari K , Takeda T , Kageyama K , Kinoshita Y
Published: June 2012

The water content in erythrocytes of subjects with borderline or established essential hypertension was measured by using gas-liquid chromatography and was found to be lower than that in normotensive controls (p less than 0.01). The water content in erythrocytes of normal controls (n = 14), borderline hypertensive subjects (n = 18), and established essential hypertensive subjects (n = 23) was (mean +/- SE) 71.0 +/- 0.2%, 69.9 +/- 0.2%, and 69.3 +/- 0.1% (vol/vol), respectively. A definite negative correlation was found between water content of erythrocytes and mean arterial pressure in normotensive and hypertensive subjects (n = 60, r = -0.59, p less than 0.001). Although there was no statistically significant between-group difference in the sodium content, the potassium content of erythrocytes from subjects with essential hypertension was significantly lower than that of normotensive controls (0.205 +/- 0.003 vs 0.222 +/- 0.004 mumol/mg dry red blood cells; p less than 0.01). There was no between-group correlation of sodium and water content in erythrocytes, but the potassium content correlated with the water content (n = 46, r = 0.49, p less than 0.001).
The pressor and metabolic effects of alcohol in normotensive subjects.
Authors: Potter J F , Watson R D , Skan W , Beevers D G
Published: June 2012

Changes in blood pressure, pulse rate, and plasma catecholamines, renin activity, cortisol, and calcium were studied in 16 normotensive subjects (eight with a family history of hypertension) for 5 hours following ingestion of alcohol-free and alcohol-loaded beer. Both systolic and diastolic blood pressure rose after alcohol consumption; maximum responses occurred at peak blood alcohol concentrations and were significantly higher than those seen after placebo. Pulse rate was also significantly higher after alcohol ingestion and continued to rise throughout the study. There was no difference in the pressor response to alcohol between the groups with and without a family history of hypertension. No difference was found in plasma norepinephrine or epinephrine levels between alcohol and placebo phases. However, subjects with no family history of hypertension had significantly higher plasma norepinephrine levels (p less than 0.01) than did those with a family history during both the alcohol and placebo phases, although baseline blood pressures were not significantly different. Plasma epinephrine level was similar in both groups. Plasma renin activity was unchanged throughout, but plasma cortisol fell during both phases. Plasma calcium showed a small but significant fall with alcohol consumption in both groups (p less than 0.001). These results indicate that in normotensive subjects alcohol ingestion causes a rise in systolic and diastolic blood pressure that is not influenced by a family history of hypertension. This effect does not appear to be sympathetically mediated but may be due to a direct vasoconstrictor effect of alcohol, possibly with an alcohol-induced shift in intracellular calcium.
Lack of effect of nifedipine on counterregulatory mechanisms in essential hypertension.
Authors: Bruun N E , Ibsen H , Nielsen F , Nielsen M D , Moelbak A G , Hartling O J
Published: June 2012

The influence of long-term nifedipine treatment on body fluid compartments, renal function, the renin-angiotensin system, and the adrenergic system was studied in 18 patients with essential hypertension. A placebo period of 4 weeks was followed by a 6-week dose-titration period. Thereafter, the dose was kept constant for an additional 6 weeks (mean dose, 51 mg/day). As compared with placebo values, diastolic blood pressure decreased approximately 12% during nifedipine treatment. Plasma volume, extracellular fluid volume, and the ratio of plasma to interstitial fluid volume did not change significantly, either in the group as a whole or in a subgroup in which pedal edema developed. Plasma concentrations of epinephrine and norepinephrine increased slightly after 2 weeks of treatment, but they returned to control values after 6 weeks of therapy. Plasma concentrations of renin, angiotensin II, and aldosterone did not change significantly. Glomerular filtration rate and renal clearances of sodium and potassium were unchanged as well. These results indicate that long-term nifedipine treatment does not lead to activation of counterregulatory mechanisms, such as fluid retention or the renin-angiotensin or adrenergic systems. This may well be of importance for the antihypertensive efficacy of nifedipine treatment.
Effect of captopril on 99mTc-diethylenetriaminepentaacetic acid renograms in two-kidney, one clip hypertension.
Authors: Nally J V , Clarke H S , Grecos G P , Saunders M , Gross M L , Potvin W J , Windham J P
Published: June 2012

In an effort to improve on the noninvasive detection of renal artery stenosis, we investigated the effect of angiotensin converting enzyme inhibition on computer-assisted 99mTc-diethylenetriaminepentaacetic acid (DTPA) renal flow studies in a canine model of two-kidney, one clip hypertension and compared these findings with clearances of inulin and p-aminohippuric acid in the stenotic and contralateral kidney before and after converting enzyme inhibition. The 99mTc-DTPA renal flow study with the converting enzyme inhibitor captopril (1.5 mg/kg bolus with 1.5 mg/min infusion) showed an increased sensitivity in the detection of unilateral renal artery stenosis over the use of the 99mTc-DTPA study alone. Captopril induced striking alterations that were most evident in the 15-minute 99mTc-DTPA renal flow study, in which all nine curves exhibited severely blunted uptake and excretion of the radionuclide. These changes were reversed during a recovery study without converting enzyme inhibition and were not seen when blood pressure was lowered with nitroprusside to a level similar to that observed during converting enzyme inhibition. The changes shown by the 99mTc-DTPA study during converting enzyme inhibition correlated with a decrease in the glomerular filtration rate of the stenotic kidney. Captopril infusion significantly decreased the glomerular filtration rate of the stenotic kidney (16.0 +/- 3.1 vs 11.0 +/- 2.5 mg/min, p less than 0.03) but not of the contralateral kidney (32.4 +/- 2.6 vs 28.4 +/- 2.8 mg/min).(ABSTRACT TRUNCATED AT 250 WORDS)
The storage form of renin in renin granules from rat kidney cortex.
Authors: Kawamura M , McKenzie J C , Hoffman L H , Tanaka I , Parmentier M , Inagami T
Published: June 2012

Renin granules were partially purified from rat kidney cortex, and a storage form of renin in the granules was examined. Renin granules were isolated by discontinuous Percoll density gradient centrifugation followed by continuous Percoll density gradient centrifugation. The partially purified fraction was free from mitochondria and microsomes, as judged by the absence of marker enzymes of these organelles, but contained some lysosomal enzyme activities. The specific renin activity was 0.58 mg angiotensin I/hr/mg protein, 500 times as active as the original homogenate. Immunochemical staining with specific antisera against rat kidney renin revealed that about 10% of the granules recovered in the partially purified fractions were stained strongly. The stored renin was not activated either by acidification or by trypsin treatment, indicating that stored renin was in the fully active form. By sodium dodecyl sulfate gel electrophoresis, the stored renin had two different molecular weights, 38,000 and 36,000, and these molecular weights were not reduced by dithiothreitol or 2-mercaptoethanol, suggesting that these renins are single-chain types as opposed to the two-chain type found in male mouse submaxillary gland. These results suggest that active renins with two different molecular weights may be released from renin granules of juxtaglomerular cells.
The influence of indomethacin on blood pressure during the infusion of vasopressors.
Authors: Rowe B P
Published: June 2012

The effect of indomethacin and its vehicle on blood pressure was studied in conscious rabbits during the infusion of three vasopressors. The cyclooxygenase inhibitor raised mean arterial pressure 12 (vehicle: 3) mm Hg during norepinephrine infusion, 5 (vehicle: 0) mm Hg during angiotensin II infusion, and 5 (vehicle: -8) mm Hg during arginine vasopressin infusion. When saline was given in place of vasopressors, indomethacin failed to alter blood pressure. Since indomethacin elevated pressure in the presence, but not the absence, of all three vasopressors, the possibility that elevation of blood pressure per se stimulates synthesis of vasodilator prostaglandins was considered. A pressor action of indomethacin was observed in ganglion-blocked animals, in which absolute blood pressure remained below normotensive levels during angiotensin II infusion. Thus, indomethacin raised arterial pressure during the infusion of norepinephrine, angiotensin II, and vasopressin, and this action was not influenced by manipulation of blood pressure. These results suggest that each vasopressor promotes prostaglandin synthesis independently to a degree sufficient to restrain its pressor action.
Assessment of left atrial function in patients with hypertensive heart disease.
Authors: Matsuda Y , Toma Y , Moritani K , Ogawa H , Kohno M , Miura T , Matsuda M , Matsuzaki M , Fujii H , Kusukawa R
Published: June 2012

Left atrial function in patients with hypertensive heart disease was compared with that in control subjects. In patients with hypertensive heart disease, the time constant of left ventricular relaxation was significantly greater than that in controls (54 +/- 18 vs 31 +/- 16 msec; p less than 0.01). The ratio of left ventricular filling volume before atrial contraction (left atrial reservoir volume/left atrial emptying volume before atrial contraction, and conduit volume/flow volume from the pulmonary vein into the left ventricle) to left ventricular stroke volume was significantly smaller than that in controls (65 +/- 13 vs 76 +/- 7%; p less than 0.05). In patients with hypertensive heart disease, the ratio of reservoir volume to stroke volume was not significantly different from that in controls, while the ratio of conduit volume to stroke volume was significantly smaller than that in controls (43 +/- 13 vs 57 +/- 9%; p less than 0.05). The latter ratio was inversely correlated with the time constant of left ventricular relaxation (r = -0.05, p less than 0.05). In patients with hypertensive heart disease, the ratio of left ventricular filling volume during atrial contraction to stroke volume was significantly larger than that in controls (35 +/- 13 vs 24 +/- 7%; p less than 0.05). The ratio of left ventricular filling volume during atrial contraction to stroke volume had a significant inverse correlation with the ratio of conduit volume to stroke volume (r = -0.84, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Cell and wall morphology of intestinal arterioles from 4- to 6- and 17- to 19-week-old Wistar-Kyoto and spontaneously hypertensive rats.
Authors: Miller B G , Connors B A , Bohlen H G , Evan A P
Published: June 2012

To determine whether vascular smooth muscle cells around intestinal arterioles of various sizes undergo comparable changes in spontaneously hypertensive rats, 4- to 6-week-old (n = 10) and 17- to 19-week-old (n = 10) rats from the Wistar-Kyoto and the spontaneously hypertensive strains were used to study the external morphology of vascular smooth muscle cells by scanning electron microscopy and the vessel wall cross-sectional characteristics by light microscopy. At the time of fixation all vascular tone had been abolished. Scanning electron microscopy analysis revealed that all Wistar-Kyoto and spontaneously hypertensive rats at a given age have spindle-shaped vascular smooth muscle cells of comparable length and longitudinal width for a given branching order of arterioles. However, normal maturation is associated with elongation and widening of the vascular smooth muscle cells. Light and scanning electron microscopy indicated that a monolayer of vascular smooth muscle cells, wrapped at almost 0 degree to the vessel's radial axis, is maintained in adult spontaneously hypertensive rats. The radial thickness of this vascular smooth muscle cell monolayer was significantly (p less than 0.025) increased for only the largest arterioles of young and adult spontaneously hypertensive rats. This radial thickening of individual vascular smooth muscle cells increased the muscular component of the wall area for the largest arterioles by about 50% in adult spontaneously hypertensive rats. Other smaller submucosal arterioles of young and adult spontaneously hypertensive rats had normal vessel wall and vascular smooth muscle cell characteristics. These data indicate that hypertrophy in the smooth muscle cell's radial dimension is the primary morphological change in intestinal arterioles of spontaneously hypertensive rats. However, the vascular smooth muscle cell hypertrophy is confined to the largest arterioles such that the remaining smaller arteriolar vessels in the spontaneously hypertensive rat retain a normal smooth muscle cell and overall wall morphology.