bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitation of hypothalamic atrial natriuretic peptide messenger RNA in hypertensive rats.
Authors: Chen Y F , Elton T S , Oparil S
Published: June 2012

Previous studies from our laboratory have shown that spontaneously hypertensive rats have increased atrial natriuretic peptide stores and reduced norepinephrine release from nerve terminals in the anterior hypothalamus. We have postulated that atrial natriuretic peptide inhibits norepinephrine release in anterior hypothalamus, reducing excitation of sympathoinhibitory neurons, increasing sympathetic outflow, and elevating blood pressure in this model. The current study tested the hypothesis that atrial natriuretic peptide messenger RNA (mRNA) transcript levels are increased in anterior hypothalamus of spontaneously hypertensive rats compared with normotensive Wistar-Kyoto rats. Atrial natriuretic peptide mRNA in hypothalamic regions was measured by the quantitative polymerase chain reaction technique using a p-SELECT mutant atrial natriuretic peptide RNA as an internal standard. Atrial natriuretic peptide mRNA from hypothalamic regions of spontaneously hypertensive and Wistar-Kyoto rats and the internal standard were coamplified in a single reaction in which the same primers were used. Since the polymerase chain reaction product of the internal standard contained a new EcoRI restriction site, it could be distinguished from the atrial natriuretic peptide mRNA product by EcoRI digestion after the polymerase chain reaction. We found regional inhomogeneity of atrial natriuretic peptide mRNA in the hypothalamus of spontaneously hypertensive and Wistar-Kyoto rats, but we found no significant differences in atrial natriuretic peptide mRNA levels in anterior, posterior, or ventral hypothalamic areas between spontaneously hypertensive rats and Wistar-Kyoto rats fed normal (1%) or high (8%) salt diets. These data do not support the hypothesis that increased atrial natriuretic peptide stores in anterior hypothalamus of spontaneously hypertensive rats are related to increased gene transcription.
Na(+)-Ca2+ exchange, myoplasmic Ca2+ concentration, and contraction of arterial smooth muscle.
Authors: Rembold C M , Richard H , Chen X L
Published: June 2012

Na(+)-Ca2+ exchange is proposed to be an important regulator of myoplasmic intracellular Ca2+ concentration ([Ca2+]i) and contraction in vascular smooth muscle. We investigated the role of Na(+)-Ca2+ exchange in regulating [Ca2+]i in swine carotid arterial tissues that were loaded with aequorin to allow simultaneous measurement of [Ca2+]i and force. Reversal of Na(+)-Ca2+ exchange, by reduction of extracellular Na+ concentration ([Na+]o) to 1.2 mM, induced a large increase in aequorin-estimated [Ca2+]i and a low [Ca2+]i sensitivity. The contraction induced by 1.2 mM [Na+]o was partially caused by depolarization and opening of L-type Ca2+ channels because 10 microM diltiazem partially attenuated the 1.2 mM [Na+]o-induced increases in [Ca2+]i. High dose ouabain (10 microM), a putative endogenous Na+,K(+)-ATPase inhibitor, increased both [Ca2+]i and force. However, the increases in [Ca2+]i and force were mostly blocked by 10 microM phentolamine, suggesting the predominant effect of ouabain was to increase norepinephrine release from nerve terminals. In the presence of 10 microM phentolamine, 10 microM ouabain slightly accentuated 1 microM histamine-induced increases in [Ca2+]i and force. The ouabain dose necessary to induce contraction in the absence of phentolamine was significantly less than the ouabain dose necessary to accentuate histamine-induced contractions in the presence of phentolamine. These results suggest that Na(+)-Ca2+ exchange exists in swine arterial smooth muscle. These data also suggest that ouabain (which should increase [Na+]i and inhibit Na(+)-Ca2+ exchange) primarily enhances contractile function in the swine carotid artery by releasing catecholamines from nerve terminals; direct action of Na+,K(+)-ATPase inhibitors on smooth muscle appears to occur only with very high doses.
On the role of renal alpha-adrenergic receptors in spontaneously hypertensive rats.
Authors: Michel M C , Jäger S , Casto R , Rettig R , Graf C , Printz M , Insel P A , Philipp T , Brodde O E
Published: June 2012

We tested the hypothesis that a genetically determined increase in renal alpha-adrenergic receptor density might be a pathophysiologically important factor in the spontaneously hypertensive rat model of genetic hypertension. In a first study, we compared renal alpha 1 and alpha 2-adrenergic receptor density with systolic blood pressure in 45 rats of an F2 generation of Wistar-Kyoto x spontaneously hypertensive rat hybrids but were unable to detect significant cosegregation between either receptor density or blood pressure. In a second study, we determined renal alpha 1- and alpha 2-adrenergic receptor density in Wistar-Kyoto and spontaneously hypertensive rat kidneys that were transplanted into an F1 generation of Wistar-Kyoto x spontaneously hypertensive rat hybrids. Although Wistar-Kyoto kidneys lowered blood pressure in these animals and spontaneously hypertensive rat kidneys increased blood pressure, renal alpha-adrenergic receptor densities were similar in membranes from both types of kidneys. Since rat kidney coexpresses alpha 1A- and alpha 1B-adrenergic receptors, we also investigated whether differential regulation of these two subtypes might conceal ongoing alterations. The alpha 1A/alpha 1B-adrenergic receptor ratio, however, was similar in Wistar-Kyoto rats, spontaneously hypertensive rats, and F1 rats transplanted with a kidney from either strain. Taken together these data do not support the hypothesis that genetically determined alterations of renal alpha-adrenergic receptor numbers play an important role in the development of elevated blood pressure in the spontaneously hypertensive rat.
Hypertensive strains and normotensive 'control' strains. How closely are they related?
Authors: St Lezin E , Simonet L , Pravenec M , Kurtz T W
Published: June 2012

The spontaneously hypertensive rat and the Dahl salt-sensitive rat are the most widely studied genetic models of hypertension. Many investigators have attempted to study the pathogenesis of hypertension by comparing these strains with their respective normotensive "controls," the Wistar-Kyoto rat and the Dahl salt-resistant rat. However, the genetic relation between each of these hypertensive strains and its corresponding normotensive control has never been clearly defined. Based on an analysis of DNA "fingerprint" patterns generated with six multilocus probes, we found that the spontaneously hypertensive rat (Charles River Laboratories, Inc.) is genetically quite different from its normotensive Wistar-Kyoto control: these strains only share approximately 50% of their DNA fingerprint bands in common. The inbred Dahl salt-sensitive rat (SS/Jr strain) (Harlan Sprague Dawley, Inc.) and the Dahl salt-resistant rat (SR/Jr strain) share approximately 80% of their DNA fingerprint bands in common. To the extent that the genes identified by DNA fingerprint analysis are representative of loci dispersed throughout the rodent genome, the current findings provide evidence of extensive genetic polymorphism between these commonly used hypertensive strains and their corresponding normotensive controls, particularly in the spontaneously hypertensive rat model. These findings, together with the fact that an enormous number of biochemical and physiological differences have been reported between these hypertensive and normotensive strains, suggest that continued comparison of spontaneously hypertensive rats with Wistar-Kyoto rats or Dahl salt-sensitive with salt-resistant rats will have limited value for investigating the pathogenesis of hypertension.
Repetitive, episodic hypoxia causes diurnal elevation of blood pressure in rats.
Authors: Fletcher E C , Lesske J , Qian W , Miller C C , Unger T
Published: June 2012

An association between chronic high blood pressure and obstructive sleep apnea has been described. We hypothesized that repetitive episodic hypoxia patterned after the hypoxia seen in sleep apnea could contribute to diurnal elevation of blood pressure. Using 12-second infusions of nitrogen into daytime sleeping chambers, four groups of male rats (250-375 g) were subjected to intermittent hypoxia (3-5% nadir ambient oxygen) every 30 seconds, 7 hours per day for up to 35 days. In one group, blood pressure was measured weekly by the tail-cuff method in conscious animals during 5 weeks of episodic hypoxia. In the other three groups, blood pressure was measured in conscious animals via femoral artery catheters at baseline and after 20, 30, or 35 days of exposure. Additional groups served as controls: two sham groups housed in identical "hypoxia" chambers received compressed air instead of nitrogen (35 days) while two other groups remained unhandled in their usual cages (35 days). Both groups challenged with 35 days episodic hypoxia showed significant increases in blood pressure compared with controls: the tail-cuff rats showed a 21 mm Hg increase in systolic pressure (p less than 0.05) and the intra-arterially measured rats a 13.7 mm Hg increase in mean arterial pressure (p less than 0.05). The 30-day exposed rats also showed a 5.7 mm Hg increase in mean pressure over baseline (p less than 0.05). Blood pressure did not change significantly from baseline in the control groups. Left ventricle-to-body weight ratio was higher in both 35-day exposed groups than in unhandled or sham controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac parasympathetic hyperresponsiveness in spontaneously hypertensive rats.
Authors: Ferrari A U , Daffonchio A , Franzelli C , Mancia G
Published: June 2012

The bradycardic response to baroreceptor stimulation is impaired in human and experimental hypertension. Because this bradycardia mainly depends on the vagus, this may reflect a reduced cardiac parasympathetic responsiveness, which would parallel the reduced cardiac adrenergic responsiveness observed in hypertension. To test this hypothesis, 12-week-old spontaneously hypertensive rats (n = 12) and normotensive Wistar-Kyoto rats (n = 11) were anesthetized with ketamine and underwent bilateral vagotomy. Cardiac parasympathetic responsiveness was assessed from the bradycardia induced by 1) graded electrical stimulation of the right efferent vagus (1-16 Hz) and 2) graded intravenous injections of methacholine (1-8 micrograms.kg-1). The slope of the linear regression between the bradycardiac response and the applied stimulus was taken as the measure of cardiac parasympathetic responsiveness. To identify the onset of possible alterations in cardiac parasympathetic responsiveness in hypertension, the study was extended to younger (8-week-old) spontaneously hypertensive (n = 11) and Wistar-Kyoto (n = 13) rats. With vagal stimulation, cardiac parasympathetic responsiveness was greater in 12-week-old spontaneously hypertensive rats than in 12-week-old Wistar-Kyoto rats (24.8 +/- 5.4 versus 10.1 +/- 1.2 beats per minute per hertz, mean +/- SEM, p less than 0.035). This was also the case with methacholine (18.8 +/- 3.5 versus 13.1 +/- 4.4 beats per minute per microgram per kilogram, p less than 0.045). In contrast, cardiac parasympathetic responsiveness was similar, with both vagal stimulation and methacholine, when tested in the younger spontaneously hypertensive and Wistar-Kyoto groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Central DuP 753 does not lower blood pressure in spontaneously hypertensive rats.
Authors: DePasquale M J , Fossa A A , Holt W F , Mangiapane M L
Published: June 2012

Oral administration of the angiotensin II receptor subtype 1 (AT1) antagonist DuP 753 causes long-lasting lowering of mean arterial pressure in spontaneously hypertensive rats. We examined whether the antihypertensive action of DuP 753 is a result of inhibition of brain angiotensin II. In normal spontaneously hypertensive rats, we found that intracerebroventricular DuP 753 (10 micrograms) blocked the pressor action of intracerebroventricular angiotensin II (100 ng); however, intracerebroventricular DuP 753 (10 micrograms) had no effect on the pressor response to 300 ng/kg angiotensin II administered intravenously (48 +/- 3 mm Hg in the presence of intracerebroventricular DuP 753 versus 49 +/- 4 mm Hg in its absence). In both normal and furosemide-treated spontaneously hypertensive rats (low Na+ diet plus furosemide), intracerebroventricular DuP 753 alone at 10 or 100 micrograms caused transient but significant pressor responses; however, no significant reduction in pressure (versus controls) was observed over the next 48 hours. In contrast to its central effects, we found that oral DuP 753 (10 or 30 mg/kg) in normal spontaneously hypertensive rats resulted in sustained mean arterial pressure decreases of up to -74 mm Hg. These data suggest that, although the pressor effect of brain angiotensin II is mediated by the AT1 receptor, blockade of these receptors does not lower blood pressure in spontaneously hypertensive rats. In the spontaneously hypertensive rat, DuP 753 depresses blood pressure by blockade of peripheral, not central, AT1 receptors.
Cardiovascular determinants of carotid artery disease. The Rotterdam Elderly Study.
Authors: Bots M L , Breslau P J , Briët E , de Bruyn A M , van Vliet H H , van den Ouweland F A , de Jong P T , Hofman A , Grobbee D E
Published: June 2012

The objective of the present study was to assess the prevalence of moderate and severe stenosis of the right carotid artery in the elderly and its associations with smoking, blood pressure, serum lipid levels, and hemostatic factors. The Rotterdam Elderly Study is a recently started single-center prospective follow-up study of a cohort of 11,854 elderly people aged 55 years or more. In 1990, 954 participants of the Rotterdam Elderly Study underwent ultrasonic duplex examination of the right internal carotid artery. A reduction of the lumen diameter of 16-49% was found in 29 people (3.0%). Severe stenosis (50% or more) was observed in 13 people (1.4%). With differences in age, sex, and body mass index taken into account, subjects with moderate-to-severe carotid artery disease had, compared with participants without stenosis, lower mean high density lipoprotein cholesterol levels (mean difference, 0.10 mmol/l; 95% confidence interval, 0, 0.20) and higher mean fibrinogen levels (difference, 0.24 g/l; 0.04, 0.45). Among them were more people with hypertension (mean difference, 16%) and more current smokers (mean difference, 13%). Factor VIIc and factor VIIIc activity was higher in subjects with carotid artery disease, without, however, reaching statistical significance (mean difference, 0.06 IU/ml [-0.01, 0.12] and 0.21 IU/ml [-0.05, 0.47], respectively). Our data suggest that hypertension, smoking, and reduced serum high density lipoprotein cholesterol levels, combined with unfavorable increases in hemostatic factors, may be related to carotid artery disease in the elderly.
Alpha-adrenergic receptors and 45Ca2+ efflux in arteries from deoxycorticosterone acetate hypertensive rats.
Authors: Storm D S , Webb R C
Published: June 2012

Increased vascular sensitivity to catecholamines characterizes mineralocorticoid hypertension. The present study investigated three possible sites that may account for this abnormality: agonist affinity, Ca2+ release from intracellular stores, and Ca2+ sensitivity of the contractile proteins. Adult male Sprague-Dawley rats underwent uninephrectomy and were implanted subcutaneously with deoxycorticosterone acetate (DOCA; 200 mg/kg, 1% NaCl:0.2% KCl drinking water, 4-6 weeks). Control rats were sham treated. Helical strips of mesenteric arteries were placed in muscle baths for measurement of isometric force development. Although the ED50 for norepinephrine was significantly lower in arteries from DOCA rats (pD2, 8.21 +/- 0.15) than in those from sham controls (pD2, 7.24 +/- 0.11), agonist affinity, determined by partial blockade with phenoxybenzamine, did not differ between the two groups. In contrast, norepinephrine-stimulated 45Ca2+ efflux in the absence of extracellular Ca2+ was significantly greater in arteries from DOCA rats than in those from sham rats. In the presence of ryanodine to deplete intracellular Ca2+ stores, force development to Ca2+ was not different in saponin-permeabilized vessels from DOCA rats, indicating that the Ca2+ sensitivity of the contractile proteins was not altered in DOCA hypertension. We conclude that increased vascular sensitivity to norepinephrine in mineralocorticoid hypertension is related to increased release of Ca2+ from a subcellular store and not to changes in agonist affinity or to the contractile protein interaction. Based on previous reports, it is likely that this abnormality reflects a postreceptor change in signal transduction, but there is also evidence to suggest that an increase in the number of alpha-adrenergic receptors may be involved.
Calcium, phosphoinositide, and 1,2-diacylglycerol responses of blood vessels of deoxycorticosterone acetate-salt hypertensive rats to endothelin-1.
Authors: Flückiger J P , Nguyen P V , Li G , Yang X P , Schiffrin E L
Published: June 2012

In previous studies a decreased responsiveness to endothelin-1 (ET-1) of conduit arteries and resistance vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats was found in comparison with uninephrectomized controls. Decreased isometric force, number of receptors, and inositol phosphate accumulation were reported in the DOCA-salt animals. In the present study effects of ET-1 on cytosolic free calcium, inositol phosphates, and 1,2-diacylglycerol were investigated in blood vessels of DOCA-salt hypertensive rats. Basal cytosolic free calcium, measured with the fluorescent dye fura-2, was 201 +/- 41 nmol/l in mesenteric arteries of DOCA-salt rats and 45 +/- 9 nmol/l in uninephrectomized controls (p less than 0.01). The maximal response of cytosolic free calcium (to 30 nmol/l ET-1) was 176 +/- 22% of the basal value for DOCA-salt and 242 +/- 6% for uninephrectomized rats (p less than 0.05). The concentration giving 50% of the maximum response was 9.0 and 6.5 nmol/l for DOCA-salt rats and controls, respectively. Inositol phosphate production after stimulation with 100 nmol/l ET-1 in the presence of LiCl was lower by at least 30% (p less than 0.01) in both aorta and mesenteric arteries of DOCA-salt hypertensive versus control rats. Basal levels of diacylglycerol in aorta were similar in DOCA-salt rats and in controls and did not respond to a 100 nmol/l ET-1 stimulation in the DOCA-salt rats, in contrast to the increase found in the control uninephrectomized rats (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of intrarenal bradykinin infusion on vasopressin release in rabbits.
Authors: Yamamoto A , Keil L C , Reid I A
Published: June 2012

Electrical stimulation of afferent renal nerves and activation of renal mechanoreceptors increase plasma vasopressin concentrations. In the present study, the effect of renal chemoreceptor activation on plasma vasopressin concentration was investigated in anesthetized rabbits. Renal chemoreceptors were activated with intrarenal infusions of bradykinin. With intrarenal infusion of bradykinin at 136 ng/min, plasma vasopressin concentration increased from 4.5 +/- 1.5 to 26.8 +/- 14.2 pg/ml at 5 minutes (p less than 0.01), whereas with infusion at 1,360 ng/min, plasma vasopressin increased from 5.9 +/- 2.0 to 54.4 +/- 16.4 pg/ml at 5 minutes (p less than 0.01). There was no significant change in plasma vasopressin during intravenous infusion of bradykinin at 136 ng/min. Infusion at 1,360 ng/min increased plasma vasopressin from 2.7 +/- 0.5 to 14.8 +/- 6.4 pg/ml (p less than 0.01), but this increase was significantly less than that produced by intrarenal infusion of the same dose of bradykinin. Similar effects on plasma vasopressin were observed during paired intrarenal and intravenous infusions of bradykinin at 136 ng/min. Renal denervation markedly reduced the vasopressin responses to intrarenal infusion of bradykinin at 136 ng/min (2.8 +/- 0.5 to 4.0 +/- 0.7 pg/ml, p less than 0.01) and 1,360 ng/min (3.2 +/- 0.7 to 7.8 +/- 1.8 pg/ml, p less than 0.05). These results indicate that bradykinin stimulates vasopressin release by an intrarenal action and suggest that this action is mediated by afferent renal nerves.
Ganglionic blockade with tetraethylammonium in conscious rats.
Authors: Petersen J S , DiBona G F
Published: June 2012

The sympathetic ganglionic blocking agent tetraethylammonium has been used as a clearance marker for the measurement of renal plasma flow, but the sympathetic ganglionic blocking dose in rats is unknown. In light of differential reflex activation of sympathetic nerve activity to heart and kidney, we compared the effect of tetraethylammonium on renal nerve activity, mean arterial pressure, and heart rate. Conscious rats were infused with either vehicle (isotonic saline) or tetraethylammonium (n = 7 in both groups). Tetraethylammonium was infused cumulatively (35 minutes per dose) in the following doses: 10(-5), 10(-4), 10(-3), 10(-2), and 10(-1) g/kg body wt per hour. Doses for 15% reduction were 10(-1) for mean arterial pressure, 0.55 x 10(-1) for heart rate, and 0.055 x 10(-1) g/kg body wt per hour for renal nerve activity. Renal nerve activity was abolished at 10(-1) g/kg body wt per hour; mean arterial pressure and heart rate were unchanged at doses lower than 10(-1) g/kg body wt per hour. The lethal dose was 1 g/kg body wt per hour. No changes were observed in vehicle-treated animals. Tetraethylammonium at 10(-1) g/kg body wt per hour resulted in an attenuated increase in renal nerve activity during acetylcholine-induced reduction in mean arterial pressure, reflecting arterial baroreceptor inhibition. We conclude that renal nerve activity is 10- and 18-fold more sensitive to sympathetic ganglionic blockade than heart rate and mean arterial pressure, respectively. When tetraethylammonium is used as a clearance marker for measurement of renal plasma flow in rats, it should be administered in doses less than 10(-2) g/kg body wt per hour.
Ischemic cardiovascular complications concurrent with administration of captopril. A clinical note.
Authors: Baker K M , Johns D W , Ayers C R , Carey R M
Published: June 2012

Administration of potent vasodepressor agents such as the angiotensin converting enzyme inhibitor, captopril, may precipitate myocardial ischemic events in patients with coronary artery disease, particularly if this treatment is preceded by a discontinuation of beta-blocking drugs such as propranolol. In one case studied, a patient experienced three episodes of angina pectoris under these conditions; in another, acute anterior myocardial infarction was suspect.
Effects of clonidine on 24-hour hormonal secretory patterns, cardiovascular hemodynamics, and central nervous function in hypertensive adolescents.
Authors: Boyar R M , Fixler D F , Kaplan N M , Graham R M , Price K P , Chipman J J , Laird W P
Published: June 2012

To assess the potential of antihypertensive drugs for interference with somatic growth and sexual development in hypertensive children, the effect of clonidine therapy on various endocrine, cardiovascular, and neuromuscular functions has been examined in five male adolescents with idiopathic hypertension. In studies done before and at the end of 4 weeks of twice-daily clonidine therapy, in an average daily dose of 0.31 mg, no significant effects were noted in the secretory patterns of growth hormone, luteinizing hormone, follicle-stimulating hormone, prolactin, cortisol, aldosterone, or testosterone, measured in blood obtained every 20 minutes for 24 hours. In blood obtained while the patients were supine and then erect, plasma renin activity and norepinephrine levels were significantly lowered after clonidine therapy. Cardiovascular responses to dynamic exercise were little altered beyond a 17% decrease in maximal oxygen consumption. The performance of fine motor skills was minimally altered. These data provide preliminary evidence that clonidine, an antihypertensive drug that affects the adrenergic nervous system, may not interfere with normal growth and maturation in adolescent males.
Hypertension produced by sodium depletion and unilateral nephrectomy: a new experimental model.
Authors: Seymour A A , Davis J O , Freeman R H , DeForrest J M , Rowe B P , Stephens G A , Williams G M
Published: June 2012

Unilateral nephrectomy of sodium-restricted male Sprague-Dawley rats produced a sustained elevation in systolic blood pressure (SBP) that was reversed by sodium repletion. A chronic intraperitoneal infuson of SQ14,225 prevented the development of hypertension in sodium-deplete unilaterally nephrectomized rats. Sodium depletion of two-kidney rats increased SBP to a lesser extent, while unilateral nephrectomy of sodium replete animals had no effect. These results provide evidence for a new model of experimental hypertension in the rat and emphasize the importance of a renal component, as demonstrated by unilateral nephrectomy, in the maintenance of normal pressure-volume relationships.
Suppression of stimulated plasma renin by clonidine in the dog.
Authors: Leavitt M L , Miller R E , Kotchen T A
Published: June 2012

The mechanism by which clonidine suppresses plasma renin activity (PRA) was investigated in dogs anesthetized with pentobarbital. Injection of clonidine (1 micrograms/kg) into the cisterna magna decreased PRA from levels stimulated by prior hemorrhage into a blood reservoir to reduce mean blood pressure by 25% (21.7 ng/ml/hr +/- 6.6 SE leads to 11.1 ng/ml/hr +/- 2.4 SE; p less than 0.05). Clonidine reduced heart rate but mean arterial pressure remained constant due to fluid movement between the reservoir and the arterial circulation of the dog. These effects could not be attributed to leakage of clonidine from the cerebrospinal fluid since intravenous administration of the same dose had no effect on PRA. In animals bilaterally splanchnicotomized at the level of the diaphragm, elevated PRA was not reduced by intracisternal clonidine. When return of reservoir fluid was prevented, animals became hypotensive after central clonidine and renin tended to increase. These results indicate that clonidine reduces stimulated renin by a central mechanism that is dependent upon the integrity of the sympathetic innervation of the kidney. Other stimuli for renin release may override the inhibitory effect of central clonidine.
Reversal of two-kidney one clip renovascular hypertension in the rat.
Authors: Thurston H , Bing R F , Swales J D
Published: June 2012

Attempted correction of two-kidney, one clip Goldblatt hypertension in the rat was carried out by three techniques; removal of the constricting clip, removal of the ischemic kidney, and converting enzyme blockade by oral captopril. Since duration of hypertension is said to be a critical factor, groups of rats were studied after short term (less than 6 weeks from clipping) and chronic (greater than 4 months) hypertension. Blood pressure, sodium balance, and plasma renin concentration (PRC) were followed before and after these correcting procedures. In a control group of animals, removal of a loose renal artery clip did not influence blood pressure and only caused trivial postoperative retention of sodium. Unclipping, however, normalized blood pressure in both short-term and chronic hypertension. After a major postoperative fall, blood pressure returned to somewhat elevated levels after nephrectomy in animals with chronic (but not short-term) hypertension. Sodium balance became markedly positive with the fall in blood pressure of operated hypertensive animals and was significantly correlated with the fall in blood pressure of operated hypertensive animals and was significantly correlated with the fall in blood pressure in these four groups at 7 days (r = 0.43). Captopril also produced a fall in blood pressure at 24 hours, with a positive sodium balance, although the relationship between blood pressure fall and sodium balance did not reach statistical significance (r = 0.30). The PRC was elevated in all hypertensive groups, although individual values overlapped with values from normal rats and nonhypertensive rats with a loose renal artery clip. The PRC fell to normal or subnormal values after either operative procedure and stabilized for at least 2 months independently of whether blood pressure fell or not. It is concluded that neither sodium retention nor renin hypersecretion maintains blood pressure in this model. Also, the rapidity of the blood pressure fall is not consistent with a role for vascular hypertrophy. The greater efficacy of unclipping suggests that the revascularized kidney after this procedure exerts a vasodepressor function independent of sodium excretion or the renin-angiotensin system.
Pathogenesis of hypertension in rats with chronic aortic baroreceptor deafferentation.
Authors: Fink G D , Kennedy F , Bryan W J , Werber A
Published: June 2012

In an attempt to produce a form of chronic neurogenic hypertension without the increased blood pressure lability which is characteristic of total baroreceptor removal, selective aortic baroreceptor deafferentation (ABD) was performed in rats. Blood pressure, blood pressure variability, heart rate, plasma and extracellular fluid volumes, and the effect of total autonomic blockade were determined in male rats 1 month following ABD. Rats with ABD had significantly higher systolic, diastolic, and mean arterial blood pressures than did sham-operated animals, but the standard deviation of pressure measured repetitively over a 1-hour period was not significantly greater. Total autonomic blockade with atropine, propranolol, and phentolamine lowered blood pressure and heart rate to a similar level in ABD and sham-operated rats. Extracellular fluid volume was not different in the two groups of rats, but plasma volume was significantly lower in rats with ABD. Despite the overall reduction in plasma volume, there was a significant positive correlation between plasma volume and blood pressure in ABD rats; no such correlation was observed in sham-operated rats. It was concluded that ABD produces a mild, chronic hypertension in rats without marked pressure lability. Although the hypertension appears to be Neurogenic in that it is ABOLIshed by autonomic blockade, volume factors also may contribute to the increased blood pressure.
Central actions and brain receptor binding of angiotensin II: Influence of sodium intake.
Authors: Mann J F , Schiffrin E L , Schiller P W , Rascher W , Boucher R , Genest J
Published: June 2012

The effects of dietary sodium on the central actions of angiotensin II (AII) and on 125I-AII binding to brain membranes were investigated in rats fed a low-sodium or control diet and implanted with a permanent cannula into the lateral cerebral ventricle. Blood pressure (BP) responses to AII injections intracerebroventricularly (i.v.t.) were blunted in sodium-deficient rats compared with controls. The BP increases in response to i.v.t.-injected Carbachol were the same in the two groups. In sodium-depleted rats, water intake was lower than in controls after AII given i.v.t.; higher after 1.5% NaCl i.v.t.; and unchanged after Carbachol i.v.t. The pressor response to AII given i.v.t. was higher in spontaneously hypertensive rats (SHR) than Wistar-Kyoto (WKY) control rats. This hyperresponsiveness to central AII was abolished by feeding a low-sodium diet. Specific 125I-AII binding in vitro to brain membranes was consistently lower in sodium-depleted rats. The results suggest that sodium depletion modifies the central actions of AII. This may be related in part to changes in the binding properties of AII receptors in the brain.
Peripheral serum corticosteroid concentrations in relation to the rat adrenal cortical circadian rhythm in androgen-induced hypertension.
Authors: Fink C S , Gallant S , Brownie A C
Published: June 2012

Adrenal function was assessed in control rats and in rats treated for 2 and 4 weeks with 17 alpha-methylandrostenediol (MAD; 17 alpha-methyl-5-androstene-3 beta-diol), a synthetic androgen known to produce hypertensive cardiovascular disease. In both groups and at both time periods, a circadian rhythm of blood corticosteroid concentrations was observed. The high point for serum corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18-hydroxy-DOC), and 11-deoxycorticosterone (DOC) concentrations occurred at the beginning of the dark period (1800 hours), and the low point occurred at the onset of the light period (0600 hours). Serum concentrations of DOC were always found to be higher in MAD-treated rats as compared with controls. The serum concentrations of B and 18-hydroxy-DOC were lower than control values at 1800 hours but higher than control concentrations at 0600 hours. The in vitro 11 beta- and 18-hydroxylation of DOC was markedly reduced with MAD treatment. In contrast, cholesterol side-chain cleavage activity was higher in animals treated with MAD. These in vitro findings correlated with spectral studies that showed a decreased binding of DOC to cytochrome P450(11) beta and increased binding of cholesterol to cytochrome P450scc. These studies suggest that MAD treatment selectively decreases 11 beta- and 18-hydroxylation in adrenal mitochondria, and this results in an increased serum concentration of DOC, a hypertensinogenic steroid. This effect of MAD on peripheral serum DOC concentration is most readily observed in quiescent animals at the high point of the circadian rhythm.
Racial contrasts in cardiovascular response tests for children from a total community.
Authors: Voors A W , Webber L S , Berenson G S
Published: June 2012

Cardiovascular risk factors in childhood were assessed by re-examining a random sample of 278 children stratified by diastolic blood pressure (BP), obtained from 3524 children aged 7-15 years in an entire geographic biracial community (Bogalusa). Re-examination included plasma renin and serum electrolytes, 24-hour urine electrolytes, heart rates, and BP at rest and in response to standardized physical stresses (orthostatic, isometric handgrip, and cold pressor tests). The BP responses in these tests were not increased in the high BP strata, which argues against a prevailing labile phase in early essential hypertension. Black children tended toward larger BP responses than whites. In black boys of the high BP stratum (n = 25), systolic supine or stressed BP were higher than for other race-sex groups; these pressures were associated negatively with plasma renin activity, which was low. White children in the high BP strata had increased heart rates, possibly indicating hyperkinetic circulation. These findings indicate that multiple mechanisms operate to contol BP at different intensities for black and white children.
Impact of hypertension information on high blood pressure control between 1973 and 1978.
Authors: Apostolides A Y , Cutter G , Kraus J F , Oberman A , Blaszkowski T , Borhani N O , Entwisle G
Published: June 2012

To determine whether the immense multifocal efforts in the United States over the past 7 years to detect and treat high blood pressure (BP), had affected the status of hypertension, data from a national household survey in 1973-74 were compared with data obtained in 1977-78 from a second non-overlapping population in the same three communities. The impact of hypertension programs was measured by assessing change over the 5-year period in BP distribution, degree of awareness, and level of treatment in the population. Our data show that a substantial improvement in the status of high BP detection, treatment, and control has occurred since the early 1970s for all age, sex, and race groups studied.
Metaischemic (post-Goldblatt) hypertensive vascular disease in rats.
Authors: Queiroz F P , Rojo-Ortega J M , Genest J
Published: June 2012

Malignant hypertension was induced in rats by aortic ligation above the left renal artery. After 7- and 28-day periods of hypertension, the characteristics of the vascular disease were studied and the kidney below the aortic ligation was removed. The blood pressure and the vascular disease were reexamined at the end of the first and fourth weeks after nephrectomy. The evolution of the vascular disease was assessed in the contralateral kidney, in the heart, and in the superior mesentery. The results obtained allowed the following conclusions: 1) when the predominant lesions are of fibrinoid necrosis and moderate intimal hyperplasia without fibromucoid changes (initial phase), the hypertension and the hypertensive vascular disease are completely reversible after the nephrectomy; 2) when the predominant lesions are proliferative endarteritis with fibromucoid changes (chronic phase), neither the hypertension nor the vascular disease are reversible after the left nephrectomy and during the period of follow-up. Therefore, the type of vascular lesion seems to be one important determinant of the reversibility of the hypertensive process after nephrectomy.
Abnormal urinary kallikrein in hypertension is not related to aldosterone or plasma renin activity.
Authors: Lawton W J , Fitz A E
Published: June 2012

The relationships between urinary kallikrein (Ukal), and plasma renin activity (PRA), urinary aldosterone (Ualdo), Na+ balance, SK+, and renal function were studied in essential hypertensives (EHT) and normals. Ukal was measured by a radiochemical esterolytic assay. We studied 18 white patients with EHT (15 men, 3 women) ages 31.6 to +/- 2.1 (SEM) yrs, BP 138 +/- 2/95 +/- 2 mm Hg. and 12 white normals (NLS) (7 men, 5 women) ages 30.2 +/- 2.3 yrs, BP 112 +/- 4/71 +/- 2 mm Hg. All received a 5-day diet of 400 mEq Na+, 80 mEq K+/day, and 5 days of 10 mEq Na+, 80 mEq K+/day. All achieved Na+ balance by Day 5. On Day 5 of the low Na+ diet, 24 hr. Ukal in EHT was 15.8 +/- 2.4 (esterase units/24 hr) vs NLS, 17.0 +/- 2.8 PRA was the same in EHT and NLS, but Ualdo was higher in NLS. (Day 5, low Na+, EHT, Ualdo = 29.4 +/0 3.3 microgram/24h. vs NLS 41.8 +/- 4.7, p less than 0.02). Analysis of individuals showed that all NLS increased Ukal after salt restriction, while 3 EHT decreased Ukal after salt restriction. This abnormal response in EHT was not related to abnormalities in Ualdo, PRA, Na+ balance, SK+, or creatinine clearance. In 3 EHT with low-renin EHT, the Ukal response was normal. In two of four patients with primary aldosteronism, Ukal was normal despite increased Ualdo. The Ukal response to salt restriction is abnormal in some EHT, unrelated to Ualdo or PRA, suggesting either a primary defect in Ukal and/or the presence of other factors modulating Ukal in EHT.
Cardiovascular reactivity to behavioral stress in young males with and without marginally elevated casual systolic pressures. Comparison of clinic, home, and laboratory measures.
Authors: Light K C , Obrist P A
Published: June 2012

Heart rate (HR), systolic (SBP), and diastolic (DBP) blood pressure levels were compared in 60 young males during various resting and stressful conditions. Subjects included 29 who had and 31 who had not shown occasional casual SBP readings greater than or equal to 135 mm Hg under low stress conditions. These groups were further divided into those who showed above-average and below-average HR increases at onset of a stressful shock-avoidance task (high vs low HR reactors). High HR reactors, who were equally distributed in both casual SBP groups, also showed higher SBP than low reactors during avoidance, and higher HR and SBP during a pre-stress rest period and two other stresses, the cold pressor test and viewing an erotic film (p's less than 0.01). During less stressful conditions (relaxation in the laboratory, family doctor readings, and self-determinations at home), no HR, SBP, or DBP differences were seen between high and low HR reactors. Subjects with casual SBPs greater than or equal to 135 showed higher mean SBP than those with casual SBPs less than 135 under all resting and stressful conditions (p's less than 0.05) and generally higher DBP as well. Highest mean SBP levels during prestress rest and later stresses were shown by subjects with both casual SBPs greater than or equal to 135 and high HR reactivity to the avoidance task, and lowest by subjects with neither trait. Incidence of parental hypertension was greater among high than low HR reactors, and greatest among high reactors with casual SBPs greater than or equal to 135, suggesting that HR reactivity to stress may help predict future hypertension.
Total and kallikrein arginine esterase activities in the urine of salt-hypertensive susceptible and resistant rats.
Authors: Sustarsic D L , McPartland R P , Rapp J P
Published: June 2012

Urinary enzymes that hydrolyze the artificial substrate alpha-N-p-tosyl-L-arginine methyl ester (TAME) were studied in Dahl salt-sensitive (S) and salt-resistant (R) rats. Total urinary TAME esterase activity (kallikrein and non-kallikrein) showed a marked increase with dialysis against water, but only in hypertensive S rats with proteinuria. This phenomenon suggests the presence of dialyzable TAME esterase inhibitor(s) in urine following renal damage, but these data do not define what urinary esterases might be affected. Partially purified urinary kallikrein exhibited a ratio of kininogenase to esterase activity which was equal for S and R rats. Thus, the marked discrepancy between kininogenase and esterase activities reported by Carretero et al. with S and R whole urine is not a function of the S and R kallikrein molecules but is probably related to interfering substances in the whole urine. Urinary kallikrein excretion was measured on individual rat samples by TAME esterase activity following dialysis and separation from non-kallikrein TAME esterase(s) using DEAE-Sephadex minicolumns. S rats had lower urinary kallikrein excretion that R when the S rats were hypertensive and showed marked proteinuria. Young S and R rats raised on low salt showed similar blood pressures and similar kallikrein excretion. High salt (8% NaCl) diet decreased kallikrein excretion in both S and R, but the decrease was greater in the S rats which became hypertensive and had increased urine protein excretion. These data suggest that the lower urinary kallikrein excretion in S rats relative to R rats is probably a consequence of hypertension and renal damage rather than a primary cause of hypertension.
Conduit artery compliance and distensibility are not necessarily reduced in hypertension.
Authors: Hayoz D , Rutschmann B , Perret F , Niederberger M , Tardy Y , Mooser V , Nussberger J , Waeber B , Brunner H R
Published: June 2012

The goal of this study was to investigate whether the elastic behavior of conduit arteries of humans or rats is altered as a result of concomitant hypertension. Forearm arterial cross-sectional compliance-pressure curves were determined noninvasively by means of a high precision ultrasonic echo-tracking device coupled to a photoplethysmograph (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring. Seventeen newly diagnosed hypertensive patients with a humeral blood pressure of 163/103 +/- 4.4/2.2 mm Hg (mean +/- SEM) and 17 age- and sex-matched normotensive controls with a humeral blood pressure of 121/77 +/- 3.2/1.9 mm Hg were included in the study. Compliance-pressure curves were also established at the carotid artery of 16-week-old anesthetized spontaneously hypertensive rats (n = 14) as well as Wistar-Kyoto normotensive animals (n = 15) using the same echo-tracking device. In these animals, intra-arterial pressure was monitored in the contralateral carotid artery. Mean blood pressures averaged 197 +/- 4 and 140 +/- 3 mm Hg in the hypertensive and normotensive rats, respectively. Despite the considerable differences in blood pressure, the diameter-pressure and cross-sectional compliance-pressure and distensibility-pressure curves were not different when hypertensive patients or animals were compared with their respective controls. These results suggest that the elastic behavior of a medium size muscular artery (radial) in humans and of an elastic artery (carotid) in rats is not necessarily altered by an increase in blood pressure.
Sympathetic nervous system in high sodium one-kidney, figure-8 renal hypertension.
Authors: Hinojosa-Laborde C , Guerra P , Haywood J R
Published: June 2012

The contribution of the sympathetic nervous system and vasopressin to the maintenance of arterial pressure was investigated in high sodium-fed rats 4 weeks after the induction of one-kidney, figure-8 renal wrap hypertension. Arterial pressure was significantly greater in renal-wrapped rats than in sham-operated animals. The contribution of the sympathetic nervous system was assessed functionally by measuring the arterial pressure response to ganglionic blockade and estimating the apparent rate of release of norepinephrine. The contribution of vasopressin was assessed by administration of the vascular antagonist d(CH2)5Tyr(Me)-AVP. Whole-animal vascular responsiveness and cardiac baroreceptor reflex sensitivity were determined by graded intravenous bolus injections of angiotensin II, vasopressin, and phenylephrine. Hypertensive rats demonstrated an exaggerated reduction in arterial pressure to autonomic blockade before and after blockade of vascular vasopressin receptors. There was a significant 27% increase in the apparent rate of release of norepinephrine into the plasma. Administration of d(CH2)5Tyr(Me)-AVP did not affect arterial pressure when given alone. However, after ganglionic blockade, inhibition of the vasopressin system elicited similar falls in blood pressure in both normotensive and hypertensive rats. Arterial pressure dose-response effects of phenylephrine, angiotensin II, and vasopressin were similar between renal-wrapped and sham-operated animals; however, cardiac baroreceptor reflex sensitivity was suppressed in the hypertensive rats. These studies indicate that the maintenance of arterial pressure in chronic, high sodium renal-wrap hypertension is associated with an augmented sympathetic nervous system function.
Na+, K(+)-adenosine triphosphatase regulation in hypertrophied vascular smooth muscle cells.
Authors: Krug L M , Berk B C
Published: June 2012

Vascular smooth muscle cell hypertrophy is a normal compensatory state that may play a pathogenic role in hypertension. Angiotensin II stimulates a hypertrophic response in cultured vascular smooth muscle cells. As part of the growth response, angiotensin II rapidly activates the Na(+)-H+ exchanger, increasing Na+ influx. Because Na+, K(+)-ATPase is the major cellular mechanism for regulating intracellular Na+, we studied the effects of angiotensin II-induced hypertrophy on Na+, K(+)-ATPase expression and activity. Angiotensin II caused rapid increases in both steady-state Na+, K(+)-ATPase activity (ouabain-sensitive 86Rb uptake) and intracellular [Na+]. Angiotensin II also caused a sustained increase in Na+, K(+)-ATPase at 24 hours with a 73% increase in maximal 86Rb uptake per milligram protein and a fourfold increase in Na+, K(+)-ATPase alpha-1 messenger RNA levels. Thus, angiotensin II hypertrophy was associated with rapid increases in Na+, K(+)-ATPase activity due to increased Na+ entry and sustained increases due to a specific increase in Na+, K(+)-ATPase expression. These data demonstrate dynamic regulation of Na+, K(+)-ATPase at the functional and molecular level and suggest that similar compensatory mechanisms should be present in vivo. Alterations in such compensatory pathways may be fundamental to the pathogenesis of hypertension.