bluuebunny/crossref_metadata_2025 huggingface dataset:
Desipramine blocks augmented neurogenic vasoconstrictor responses to epinephrine.
Authors: Floras J S , Sole M J , Morris B L
Published: June 2012

The forearm vasoconstrictor response to lower body negative pressure (LBNP), a reflex stimulus to norepinephrine release, can be augmented by a prior brachial artery infusion of epinephrine. We wished to determine whether this sustained aftereffect of epinephrine could be replicated by systemic infusion and, if so, whether it could be prevented by prior uptake-1 blockade with desipramine. Eight normal men (mean age 30 years) were studied on two separate study days at least 1 week apart, 2.5 hours after taking, at random, either desipramine (125 mg p.o.) or placebo. Forearm vascular resistance was measured at rest and at the end of 6 minutes of LBNP at -40 mm Hg. This was done both before and 30 minutes after a 60-minute infusion of epinephrine (1.5 micrograms/min i.v.). From similar baselines, the forearm vasoconstrictor response to LBNP was significantly augmented 30 minutes after epinephrine on the placebo day (+17 +/- 4 vs. +12 +/- 3 resistance units, mean +/- SEM, p less than 0.01) but not on the desipramine day (+14 +/- 2 vs. +16 +/- 3 resistance units). The heart rate response to LBNP was also greater after epinephrine on the placebo day (+20 +/- 3 vs. +16 +/- 2 beats/min, p less than 0.05). Mean arterial pressure was higher after epinephrine infusion on the placebo (p less than 0.01) but not on the desipramine day.(ABSTRACT TRUNCATED AT 250 WORDS)
Race, sex, and family history of hypertension and erythrocyte sodium pump [3H]ouabain binding.
Authors: Songu-Mize E , Alpert B S , Willey E S
Published: June 2012

We studied the binding properties of [3H]ouabain to erythrocytes from normotensive children (n = 83) between the ages of 10 and 18 years (mean resting arterial pressure: 102/57 mm Hg) from normotensive and essential hypertensive parents. Arterial blood pressures of 101/57 and 104/57 mm Hg (subjects with normotensive and hypertensive parents, respectively) were not significantly different between the two groups. Forty-four children had normotensive parents and 39 had hypertensive parents, 51 were white and 32 were black, and 41 were girls and 42 were boys. By using the [3H]ouabain-binding technique, we determined the density of sodium pump sites and the equilibrium dissociation constants in erythrocytes from these children. Possible effects of race, sex, or parental hypertension status on pump sites and dissociation constants were tested with a three-way analysis of variance (ANOVA). Race had a major effect on the dissociation constant: blacks had a significantly higher value than did whites (p = 0.002). We also found a race by sex by parental hypertension status interaction (p = 0.04) with black girls with hypertensive parents having the highest value. There was no effect of race, sex, or status on sodium pump site density. Age, height, weight, resting arterial blood pressure, and plasma Na+ and K+ concentrations did not correlate with the dissociation constants. These data suggest that, among the groups we studied, black girls with hypertensive parents had erythrocytes with the lowest binding affinity for ouabain.(ABSTRACT TRUNCATED AT 250 WORDS)
Atrial natriuretic factor-potentiating and antihypertensive activity of SCH 34826. An orally active neutral metalloendopeptidase inhibitor.
Authors: Sybertz E J , Chiu P J , Vemulapalli S , Watkins R , Haslanger M F
Published: June 2012

The effects of SCH 34826, an orally active neutral metalloendopeptidase inhibitor, on responses to atrial natriuretic factor-(103-125) or -(99-126) and on blood pressure were evaluated in rats. SCH 34826 (10, 30, and 90 mg/kg s.c. and 90 mg/kg p.o.) potentiated the antihypertensive action of atrial natriuretic factor (30 micrograms/kg i.v.) in conscious spontaneously hypertensive rats. SCH 34826 (90 mg/kg) also potentiated the diuretic and natriuretic responses to atrial natriuretic factor (30 micrograms/kg i.v.) as well as the plasma levels achieved after peptide injection. SCH 34826 significantly reduced blood pressure in the conscious deoxycorticosterone acetate-salt hypertensive rat, at doses of 90 mg/kg s.c. (-35 +/- 12 mm Hg), 10 mg/kg p.o. (-30 +/- 7 mm Hg), and 90 mg/kg p.o. (-45 +/- 6 mm Hg). SCH 34826 was devoid of acute antihypertensive activity in the spontaneously hypertensive rat but reduced blood pressure by day 3 of a 5-day treatment schedule. SCH 34826 (90 mg/kg s.c.) enhanced urine volume output in the deoxycorticosterone acetate-salt rat (2.78 +/- 0.6 vs. 1.27 +/- 0.3 ml/100 g/3 hr in vehicle-control rats, p less than 0.05). SCH 34826 (90 mg/kg s.c.) increased plasma levels of atrial natriuretic factor at 1 hour (753 +/- 89 vs. 451 +/- 79 pg/ml in vehicle-treated rats, p less than 0.05) but not 3 hours after dosing. The renal excretion of atrial natriuretic factor (3,092 +/- 1,089 vs. 21 +/- 6 pg/100 g/3 hr in vehicle-treated rats, p less than 0.05) and cyclic guanosine monophosphate (2,131 +/- 509 vs. 879 +/- 168 pg/100 g/3 hr in vehicle-treated rats, p less than 0.05) was markedly elevated by SCH 34826 in deoxycorticosterone acetate-salt rats. These studies suggest that neutral endopeptidase inhibition may represent a new approach to treatment of some forms of hypertension.
Atrial natriuretic factor and arterial baroreceptor reflexes in unanesthetized rats.
Authors: Ferrari A U , Daffonchio A , Sala C , Gerosa S , Mancia G
Published: June 2012

The modulation exerted by atrial natriuretic factor (ANF) on the cardiac and vascular influences of arterial baroreceptors was investigated in two groups of unanesthetized, chronically instrumented normotensive rats. In group 1, the reflex control of heart rate was assessed by graded baroreceptor stimulations and deactivations obtained by intravenous boluses of phenylephrine and nitroprusside. Under either circumstance, baroreceptor reflex sensitivity was expressed as the linear regression slope relating the chronotropic responses to the drug-induced mean arterial pressure changes. In group 2, right common carotid occlusion was performed in rats with their aortic and left carotid sinus baroreceptors denervated to assess the baroreceptor control of blood pressure; the reflex response was quantitated as the peak blood pressure rise observed during the maneuver. The reflex studies were performed before and during atriopeptin III infusion (0.15-0.20 micrograms/kg/min for 60 minutes). ANF augmented the bradycardic response to phenylephrine by 102.5 +/- 29% (p less than 0.01), reduced the tachycardic response to nitroprusside by 67.7 +/- 6.4% (p less than 0.01), and failed to modify the pressor response to carotid occlusion (-6.8 +/- 2.1%, p = NS). In a separate group of rats infused with low dose nitroprusside, no change in the baroreceptor-heart rate reflex was observed. ANF infusion (0.20 micrograms/kg/min) performed in further separate groups of conscious rats raised plasma ANF to 480 +/- 58 fmol/ml. Values in control vehicle-infused rats were 50 +/- 8 fmol/ml. Vascular reactivity (pressor response to intravenous phenylephrine boluses in anesthetized, sinoaortic-denervated rats) was only minimally reduced by ANF.(ABSTRACT TRUNCATED AT 250 WORDS)
Chromogranin A. Storage and release in hypertension.
Authors: Takiyyuddin M A , Cervenka J H , Hsiao R J , Barbosa J A , Parmer R J , O'Connor D T
Published: June 2012

The chromogranins/secretogranins are a family of acidic, soluble proteins with widespread neuroendocrine distribution in secretory vesicles. Although the precise function of the chromogranins remains elusive, knowledge of their structure, distribution, and potential intracellular and extracellular roles, especially that of chromogranin A, has greatly expanded during recent years. Chromogranin A is coreleased with catecholamines by exocytosis from vesicles in the adrenal medulla and sympathetic nerve endings. Thus, measurement of its circulating concentration by radioimmunoassay may be a useful probe of exocytotic sympathoadrenal activity in humans, under both physiological and pathological conditions. Here, we explore the storage, structure, and function of chromogranin A, and parameters that influence its circulating levels. We have also measured plasma chromogranin A concentrations in different groups of patients with hypertension, including those with pheochromocytoma.
5-Hydroxytryptamine kinetics and activation of blood platelets in patients with essential hypertension.
Authors: Fetkovska N , Amstein R , Ferracin F , Regenass M , Bühler F R , Pletscher A
Published: June 2012

To investigate possible alterations in 5-hydroxytryptamine (5HT) kinetics and sensitivity of blood platelets in patients with essential hypertension, 45 essential hypertensive patients and 45 normotensive healthy subjects matched in pairs for age, sex, and smoking status were compared. There were 18 women and 27 men in each group, ranging from 30 to 73 years of age. Results of essential hypertensive patients differed in several ways from those of normotensive subjects. In essential hypertensive patients, maximal 5HT uptake velocity (Vmax) decreased with increasing blood pressure and age and was reduced the most in older men. Vmax was positively related to the EC50 of 5HT for inducing a shape change reaction. In essential hypertensive patients, both Vmax of 5HT uptake and the EC50 of 5HT for shape change showed positive correlations with the 5HT content in platelets; the former relation was different between the essential hypertensive and normotensive groups (F = 5.53; p = 0.02). These results indicate reduced uptake of 5HT by blood platelets and suggest enhanced 5HT plasma concentrations in local areas, especially vascular lesions in essential hypertensive patients. Increased periplatelet concentrations of 5HT may lead to preactivation of platelets and possibly stimulation of vascular smooth muscle via their 5HT2-receptors. These changes are likely to be involved in the pathogenesis of increased thromboembolic complications in essential hypertensive patients, particularly in older men.
Tonic cardiovascular effects of angiotensin II in the ventrolateral medulla.
Authors: Sasaki S , Dampney R A
Published: June 2012

The rostral and caudal parts of the ventrolateral medulla play a major role in the control of blood pressure. Both regions contain a high density of receptor binding sites for angiotensin II, and it has been shown previously that microinjection of angiotensin II into the rostral ventrolateral medulla causes a rise in blood pressure. The aims of this study were to determine the cardiovascular effects of microinjection of angiotensin II and its specific antagonist [Sar1Thr8]angiotensin II into the caudal ventrolateral medulla and to characterize the regional vascular effects elicited by both compounds in the rostral ventrolateral medulla. Microinjections of angiotensin II (0.2-20 pmol) into histologically verified sites in the caudal ventrolateral medulla of anesthetized baroreceptor-denervated rabbits produced dose-dependent decreases in blood pressure and renal sympathetic nerve activity, whereas microinjection of [Sar1Thr8]angiotensin II (40 pmol) produced increases in these variables. In the rostral ventrolateral medulla, angiotensin II (0.02-20 pmol) elicited a dose-dependent increase in blood pressure, iliac vascular resistance, and renal sympathetic nerve activity, whereas [Sar1Thr8]angiotensin II (40 pmol) produced decreases in these variables. The effects on heart rate elicited by either compound in the rostral or caudal ventrolateral medulla were small but were in the same direction as the other cardiovascular variables. In contrast, angiotensin II had no detectable effect on sympathoexcitatory neurons within the rostral dorsomedial medulla, a region that lacks angiotensin II receptor binding sites. The results indicate that endogenous angiotensin II acts on specific receptors within the rostral and caudal parts of the ventrolateral medulla and has a tonic excitatory action on sympathoexcitatory and sympathoinhibitory neurons within these respective regions.
Treatment of hypertension in the elderly: II. Cognitive and behavioral function. Results of a Department of Veterans Affairs Cooperative Study.
Authors: Goldstein G , Materson B J , Cushman W C , Reda D J , Freis E D , Ramirez E A , Talmers F N , White T J , Nunn S , Chapman R H
Published: June 2012

This study was designed to determine whether blood pressure reduction, per se, causes adverse effects on cognitive and behavioral function in elderly hypertensive patients. Men with mild-to-moderate diastolic hypertension who had passed their 60th birthday were entered into the trial. After a placebo washout period, they were assigned in a randomized, double-blind manner to one of two groups receiving hydrochlorothiazide (either 25 mg once or twice daily or 50 mg once or twice daily). Responders entered a 1-year maintenance period. Nonresponders were randomly assigned to double-blind treatment with hydralazine, methyldopa, metoprolol, or reserpine added to the diuretic therapy. During the placebo and treatment periods, patients underwent a battery of psychometric tests designed to assess cognitive function, motor skills, memory, and affect. A separate questionnaire assessed the patient's ability to perform activities of daily living. A subset of patients blindly being treated with placebo received the same battery of tests as a control for practice effect. The results showed that there was similar improvement on the psychometric tests between those patients whose blood pressure was successfully reduced and the placebo-treated control group. Therefore, the practice effect did not obscure a true deterioration in function. There were no substantive differences between the lower and higher doses of diuretic or among the four drugs added to the diuretic, although there were qualitative differences in side effects. We conclude that blood pressure reduction, per se, does not adversely affect cognitive and behavioral function in elderly hypertensive patients and that antihypertensive treatment is safe and effective in these patients.
Effects of interstrain renal transplantation on NaCl-induced hypertension in Dahl rats.
Authors: Morgan D A , DiBona G F , Mark A L
Published: June 2012

Previous studies using renal transplantation suggested that the genotype of a homograft kidney plays the primary role in determining chronic arterial pressure levels in Dahl salt-sensitive (DS) and salt-resistant (DR) rats, but this conclusion derived largely from observations during low NaCl diet. Recent studies indicate that extrarenal factors, including the sympathetic nervous system, play a critical role in the development of NaCl-induced hypertension in DS rats. To assess the contribution of extrarenal and renal factors in the development of NaCl-induced hypertension in Dahl rats, we performed renal transplantation in DS and DR rats. Both kidneys of the recipient were removed at the time of transplantation. Four groups of rats (n = 18-23 in each group) were fed a high NaCl (8.0%) diet for 2 weeks after renal transplantation. These included DRR, DRS, DSR, and DSS, where DR or DS indicates the recipient strain and the subscript indicates the homograft strain. Mean arterial pressure was measured from the femoral artery in conscious rats. On a high NaCl diet, mean arterial pressure was significantly lower (p less than 0.05) in DRR (103 +/- 2 mm Hg; mean +/- SEM) compared with DRS (145 +/- 5 mm Hg), DSR (151 +/- 7 mm Hg), and DSS (160 +/- 5 mm Hg). The finding that DR rats with a DS kidney (DRS) developed hypertension during high NaCl diet confirms the concept that the kidney plays an important hypertensinogenic role in the Dahl strain. The fact that DS rats with a DR kidney (DSR) also developed hypertension indicates that extrarenal factors also contribute significantly to NaCl-induced hypertension in DS rats.
Prostacyclin and thromboxane biosynthesis in mild essential hypertension.
Authors: Minuz P , Barrow S E , Cockcroft J R , Ritter J M
Published: June 2012

The possibility that prostacyclin or thromboxane biosynthesis is abnormal in patients with established mild essential hypertension was investigated in 46 patients. These eicosanoids have opposing effects both on vascular smooth muscle and on platelets. An imbalance in their biosynthesis could therefore influence both vascular tone and predisposition to thrombosis. We studied the relation between blood pressure and the biosynthesis of prostacyclin and thromboxane A2 by measuring urinary excretion rates of stable breakdown products of prostacyclin (6-oxo-prostaglandin F1 alpha and 2,3-dinor-6-oxo-prostaglandin F1 alpha) and of thromboxane A2 (thromboxane B2 and 2,3-dinor-thromboxane B2) using immunoaffinity chromatography and gas chromatography/electron capture mass spectrometry. Excretion rates of both of the prostacyclin-derived products ranged from less than 5 to more than 100 ng/g creatinine; each was significantly negatively correlated with blood pressure (r = 0.36-0.45). A reduction of 2,3-dinor-6-oxo-prostaglandin F1 alpha excretion of 100 ng/g creatinine was associated with an increase in arterial pressure of 14 mm Hg (systolic) and 8 mm Hg (diastolic) in patients who had been without antihypertensive medication for 2 weeks. The same reduction in 6-oxo-prostaglandin F1 alpha excretion was associated with an increased pressure of 19 mm Hg (systolic) and 12 mm Hg (diastolic) (2p less than 0.05 for diastolic pressure and 2p less than 0.01 for systolic pressure in each case). There were similar correlations between the excretion rates of these products and blood pressure in the same patients while they were receiving antihypertensive therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell calcium, oncogenes, and hypertrophy.
Authors: Marban E , Koretsune Y
Published: June 2012

The cellular mechanisms of cardiac hypertrophy remain unclear despite tantalizing clues gleaned from a variety of experimental approaches. Here we examine the hypothesis that an increase in cytosolic free Ca2+ concentration ([Ca2+]i) triggers the expression of proto-oncogenes, which in turn direct the characteristic increase in protein synthesis. New results from perfused ferret hearts are presented demonstrating that [Ca2+]i increases as a direct consequence of an elevation in perfusion pressure. It therefore seems plausible that [Ca2+]i constitutes the crucial link between the initial stimulus for hypertensive hypertrophy (elevated perfusion pressure) and the secondary alterations in gene expression. Nevertheless, further investigation will be required to establish whether changes in [Ca2+]i are necessary or sufficient to stimulate myocardial cell growth.
Effects of NG-monomethyl-L-arginine and L-arginine on acetylcholine renal response.
Authors: Lahera V , Salom M G , Fiksen-Olsen M J , Raij L , Romero J C
Published: June 2012

Intrarenal infusion of acetylcholine in meclofenamate-treated dogs significantly increased renal blood flow, diuresis, and natriuresis. Intrarenal infusions of either NG-monomethyl-L-arginine (inhibitor of endothelium-derived relaxing factor formation), or L-arginine (precursor of endothelium-derived relaxing factor formation) did not modify basal levels of those parameters. However, the infusion of NG-monomethyl-L-arginine inhibited the acetylcholine-induced increases in renal blood flow and diuresis without affecting natriuresis, which increased significantly. The infusion of L-arginine failed to further enhance hemodynamic and excretory effects elicited by acetylcholine. The concomitant infusion of L-arginine and NG-monomethyl-L-arginine did not change renal blood flow, urine flow, or sodium excretion rate. L-Arginine administration prevented the inhibitory effect of NG-monomethyl-L-arginine on acetylcholine-induced renal vasodilatation and diuresis. Glomerular filtration rate and mean arterial pressure did not change throughout the experiment. The results indicate that the vasodilatory and diuretic responses to intrarenal acetylcholine in meclofenamate-treated dogs are largely dependent on endothelium-derived relaxing factor.
Differences in blacks and whites with essential hypertension: biochemistry and endocrine. State of the art lecture.
Authors: Falkner B
Published: June 2012

Overall, there is agreement that the origins of hypertension have a genetic basis. The genetic factors interact with environmental factors that influence expression and intensity of the disorder. As summarized in Table 1, there is evidence from the literature to identify pathways for the development of hypertension in blacks. Organ pathology, characteristic of the clinical phenotypic hypertension, consists of increased peripheral vascular resistance and left ventricular hypertrophy, and, particularly in blacks, nephrosclerosis. In this scheme, an intermediate phenotype is a biochemical or endocrine marker of gene expression that participates in the regulation of blood pressure. Intermediate phenotypic characteristics of essential hypertension include sodium sensitivity, adrenergic activity, cation transport, and endocrine function including renin-angiotensin-aldosterone, kallikrein-kinin, and prostaglandin. Another intermediate phenotype to be included in this discussion is insulin resistance. These intermediate phenotypes of cell and subcellular function are regulated by candidate genes. Alternatively, an intermediate phenotype can be expressed in response to another intermediate phenotype. For example, sodium sensitivity could be mediated by the cation transport mechanism of Na,K-ATPase, or insulin resistance could be induced by an elevated level of adrenergic activity. Gene expression of the intermediate phenotype is also modulated by environmental factors such as dietary sodium, potassium, or calcium, and social stresses or patterns of physical activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased transcription of a major stress gene in spontaneously hypertensive mice.
Authors: Hamet P , Malo D , Tremblay J
Published: June 2012

Environmental stress factors, including temperature, modify the severity of hypertension, a genetic disease. Hypertensive animals and humans respond abnormally to heat exposure, and this abnormality is reflected at the cellular level by an increment in a major stress (heat-shock) gene expression. The present studies demonstrate that increased hsp70 gene expression is due to its heightened transcription rate. The genetic basis of environmental susceptibility to hypertension may thus involve an abnormal control of heat shock genes.
Cardiac afferents attenuate renal sympathetic baroreceptor reflexes during acute hypertension.
Authors: Dorward P K , Bell L B , Rudd C D
Published: June 2012

We have studied the effect of acute hypertensive episodes on the renal sympathetic baroreceptor reflex in conscious rabbits and the role played by cardiac afferents and endogenous opiate mechanisms. Renal sympathetic nerve activity was recorded during brief perivascular balloon-induced ramp changes in mean arterial pressure before and during 40-minute elevations in resting pressure. Methoxamine infusion was adjusted to increase pressure by +30 and +45 mm Hg in the presence of autonomic blockade of the heart with atenolol and methscopolamine. Experiments were repeated in other rabbits after blocking cardiac afferents with 5% intrapericardial procaine or during intravenous naloxone (4-6 mg/kg, then 0.12 mg/kg/min). We found a progressively severe attenuation of the renal sympathetic baroreceptor reflex during increasing elevations in resting pressure. The upper plateau and range of the reflex curve were both reduced by one third and two thirds during moderate and severe hypertension, respectively. The average gain fell by 64% and 87%, and the range-independent gain and hypotensive reversal response were also reduced. There was no resetting of the reflex to higher pressures as would be expected. One third of the reflex inhibition was prevented by blocking cardiac afferents; none of it was affected by intravenous naloxone, which had previously been shown to reverse the renal baroreceptor reflex depression elicited by hemorrhagic hypotension. Factors possibly responsible for the remaining two thirds of the hypertension-induced sympathoinhibition are suggested to be either central depression of sympathetic tone after elevation of arterial baroreceptor discharge during the hypertensive episode or additional inhibitory afferent input arising from the pulmonary circulation.
Activation of endothelial L-arginine pathway in resistance arteries. Effect of age and hypertension.
Authors: Dohi Y , Thiel M A , Bühler F R , Lüscher T F
Published: June 2012

In conduit arteries, nitric oxide is formed from L-arginine in the endothelium and released after stimulation with acetylcholine. The contribution of the L-arginine pathway and the effects of age and hypertension on endothelium-dependent vascular regulation were studied, using a video dimension analyzer, in pressurized and perfused mesenteric resistance arteries of 8- and 16-20-week-old Wistar-Kyoto and spontaneously hypertensive rats. Norepinephrine and phenylephrine caused contractions, which were similarly augmented after removal of the endothelium. NG-Monomethyl-L-arginine, an inhibitor of nitric oxide formation, augmented the contraction, but less than endothelial removal. Acetylcholine caused endothelium-dependent relaxations that were much more pronounced with intraluminal than with extraluminal application. NG-Monomethyl-L-arginine, methylene blue, and hemoglobin only partially inhibited the response. With aging, the endothelium-dependent inhibition of the response to norepinephrine decreased in Wistar-Kyoto rats; in spontaneously hypertensive rats this inhibition was smaller as compared with age-matched Wistar-Kyoto rats. In Wistar-Kyoto rats, the difference between intraluminal and extraluminal activation became more pronounced in adult rats. In the adult but not the young spontaneously hypertensive rats, the response to intraluminal but not extraluminal acetylcholine was reduced as compared with Wistar-Kyoto rats. Thus, in mesenteric resistance arteries of the rat, nitric oxide is released from L-arginine under basal conditions and after stimulation with acetylcholine but only in part accounts for endothelium-dependent responses. With aging and hypertension, the inhibitory effects of the endothelium against norepinephrine-induced contractions decrease. In hypertension, the intraluminal but not extraluminal activation of the release of endothelium-derived relaxing factors is impaired.
Systemic and regional hemodynamics in patients with salt-sensitive hypertension.
Authors: Fujita T , Ando K , Ogata E
Published: June 2012

Twenty-two patients with normal plasma renin and essential hypertension were classified as "salt-sensitive" (SS) (n = 9) or "non-salt-sensitive" (NSS) (n = 13) from an increase in mean blood pressure with changes in sodium intake from 25 to 250 meq/day. With the high sodium diet, the SS patients gained more weight (p less than 0.05), retained more sodium (p less than 0.05), and had a greater increase in cardiac output (p less than 0.05). Despite the markedly increased cardiac output, systemic vascular resistance did not change with sodium loads in the SS patients, whereas the NSS patients had a significant decrease in systemic vascular resistance. Thus, the greater increase in blood pressure with sodium loads in SS patients can be attributed not only to an increase in cardiac output, possibly resulting from greater sodium retention, but also to inappropriately elevated systemic vascular resistance. Concomitant with a greater increase in cardiac output, the SS patients had a greater increase in forearm blood flow with sodium loading than the NSS patients (p less than 0.02). In contrast, blood flow to the kidney and the liver was not significantly changed in either group; renal (p less than 0.05) and hepatic (p less than 0.01) vascular resistance increased significantly in SS patients but remained unchanged in NSS patients. Thus, evidence presented suggests that the greater increase in blood pressure with sodium loads seems to be characterized by a very inhomogenous distribution of local flow and resistance in SS patients; renal and hepatic blood flow remains essentially unchanged and skeletal muscle blood flow receives almost all of the increase in cardiac output. Moreover, systemic vascular resistance changes did not reflect the resistance of individual beds because vasoconstriction appeared in the kidney and the splanchnic area but was masked by prominent vasodilation in the skeletal muscle. Because this hemodynamic pattern is similar to the pattern evoked during defense reaction, it is suggested that sympathetic overactivity on a selective basis might be involved in the impaired renal function for sodium excretion and the increase in blood pressure with sodium loads in SS patients.
Role of epinephrine in the development of hypertension in Dahl salt-sensitive rats.
Authors: Johnson M D , Kotchen T A
Published: June 2012

The present experiments were designed to test the hypothesis that adrenal epinephrine contributes to the development of hypertension in the Dahl salt-sensitive (DS) rat. All studies were carried out in conscious male DS and Dahl salt-resistant (DR) rats weighing 200-240 g. An indwelling femoral arterial catheter was placed for blood sampling and measurement of blood pressure. After 5 days of either a high salt (7% NaCI) or a normal salt (1% NaCl) dietary regimen, DS and DR rats were subjected to an acute stress paradigm (graded electrical footshock). There were no differences in basal plasma catecholamine concentrations or in the acute pressor responses to graded footshock between the four substrain/diet groups. However, in both DS and DR rats, plasma epinephrine responses to acute footshock were greater on a 7% than on a 1% NaCl diet. Additional groups of DS rats were treated with an inhibitor of adrenal phenylethanolamine N-methyltransferase, SK&F 29,661 (1-2 g/kg body wt/day) or with vehicle. Three days after placement of an arterial catheter, rats were placed on a 7% NaCl diet, and blood pressure was measured daily for an additional 3 weeks. Although SK&F 29,661 treatment was effective in reducing adrenal epinephrine content and apparent release by approximately 80%, treatment did not alter the time course of salt-induced changes in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
A kallikrein-like enzyme in blood vessels of one-kidney, one clip hypertensive rats.
Authors: Nolly H , Carretero O A , Scicli G , Madeddu P , Scicli A G
Published: June 2012

Active and inactive kallikrein or a kallikrein-like enzyme are found in the aorta, vena cava, and tail artery and veins of the rat. We studied the concentration of vascular kininogenase in rats with one-kidney, one clip renovascular hypertension and in unilaterally nephrectomized normotensive rats. Six weeks after surgery, active and total vascular kininogenase activity (active plus trypsin-activated) was measured. Blood pressure was 212 +/- 4 mm Hg in the hypertensive rats (n = 33) and 120 +/- 1 mm Hg in the normotensive rats (n = 32) (p less than 0.001). Active kininogenase was lower in the hypertensive rats; although the difference was not significant in the thoracic aorta (56 +/- 8 versus 77 +/- 15), it was highly significant in the abdominal aorta (63 +/- 13 versus 167 +/- 17, p less than 0.001) and tail artery (48 +/- 8 versus 197 +/- 31, p less than 0.003). Total vascular kininogenase activity (active plus trypsin-activated) was lower in the hypertensive rats in all arteries examined: thoracic aorta (183 +/- 16 versus 380 +/- 38, p less than 0.003), abdominal aorta (565 +/- 61 versus 1,093 +/- 74, p less than 0.001), and tail artery (532 +/- 112 versus 1,243 +/- 135, p less than 0.003). Active kininogenase in the vena cava was higher in the hypertensive rats (213 +/- 56 versus 131 +/- 31); however, this difference was not statistically significant, whereas in the tail veins it was highly significant (1,803 +/- 221 versus 771 +/- 79, p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)
Interleukin-2 does not attenuate hypertension in spontaneously hypertensive rats.
Authors: Pascual D W , Jin H K , Bost K L , Oparil S
Published: June 2012

It was recently reported that interleukin-2, when administered as a single bolus injection (5,000 units/kg), could prevent the development of hypertension in young spontaneously hypertensive rats and lower blood pressure to normotensive levels in spontaneously hypertensive rats with established hypertension. Consequently, efforts were made to duplicate this finding. Male spontaneously hypertensive rats (35 days old) were injected subcutaneously with 50,000 units/kg (3,500 units/rat) of recombinant interleukin-2 (Amgen) and had systolic blood pressure measured twice weekly by the tail-cuff technique. Systolic blood pressure in the interleukin-2-treated group was not significantly different from the vehicle-treated control group at any time point over 32 days of follow-up. A second injection of recombinant interleukin-2 (5,000 units/kg) was administered 32 days after the first injection. Again, no reduction in blood pressure was observed in the interleukin-2-treated group over an additional 38 days. Mean arterial pressure (+/- SEM) measured via intra-arterial cannula in conscious rats at age 105 days (38 days after the second treatment) was 168.5 +/- 3.5 mm Hg in interleukin-2-treated spontaneously hypertensive rats and 170.3 +/- 3.6 mm Hg in vehicle-treated controls. Both recombinant interleukin-2 preparations conformed to their respective manufacturer's indicated specific activity as determined by the ability of the interleukin-2 to induce proliferation of the interleukin-2-dependent cell line HT-2. Thus, this study demonstrated that interleukin-2 was ineffective in preventing or attenuating hypertension in spontaneously hypertensive rats.
Injection of 1,25-(OH)2 vitamin D3 enhances resistance artery contractile properties.
Authors: Bukoski R D , Wang D B , Wagman D W
Published: June 2012

The hypothesis that 1,25-dihydroxyvitamin D3 [1,25-(OH)2 vitamin D3] modulates vascular smooth muscle contractile function was tested. 1,25-(OH)2 vitamin D3 (50 ng/day) was administered by intraperitoneal injection over a 3-day period to 13-15-week-old male spontaneously hypertensive and Wistar-Kyoto normotensive rats. On the fourth day, serum was prepared and contractile force generation of isolated mesenteric resistance arteries was examined. Treatment with 1,25-(OH)2 vitamin D3 approximately doubled serum levels of the hormone and increased ionized and total serum Ca2+ and phosphate by 5-10%. No effect on blood pressure was detected. 1,25-(OH)2 vitamin D3 injection in both strains enhanced maximal stress generation to norepinephrine and serotonin by 30-40%, with no effect on apparent sensitivity of the vessels to the agonists. To assess the effect of a maneuver that elevates serum ionized Ca2+ without the addition of exogenous hormone, maximal stress generation was examined in resistance arteries isolated from rats fed diets containing 0.5% or 2% calcium over a 6-7-week period. Maximal stress generation in response to norepinephrine was greater in vessels from rats of both strains maintained on 0.5% calcium. It is concluded that 72-hour in vivo treatment with 1,25-(OH)2 vitamin D3 increases contractile force-generating capacity of resistance arteries without affecting blood pressure. It is proposed that this action of 1,25-(OH)2 vitamin D3 is the result of a direct action of the hormone on the vascular wall.
Enalapril and renal injury in spontaneously hypertensive rats.
Authors: Feld L G , Cachero S , Van Liew J B , Zamlauski-Tucker M , Noble B
Published: June 2012

Rats of the spontaneously hypertensive strain develop kidney damage that resembles the nephropathy seen in some cases of human essential hypertension. Previous studies with a triple drug antihypertensive regimen indicated that proteinuria and glomerular histopathology in spontaneously hypertensive rats might develop despite long-term effective control of systemic blood pressure. To investigate further the relation between hypertension and kidney disease, a group of spontaneously hypertensive rats were treated with enalapril at 15 weeks of age. Blood pressure, protein excretion, and kidney function were measured in those rats at regular intervals during the next year and a half and were compared with untreated spontaneously hypertensive rats and the normotensive Wistar-Kyoto parent strain. Kidney tissue samples from all three groups, collected at autopsy, were stained by immunohistochemical and conventional methods to assess the relative severity and nature of kidney damage. Although enalapril therapy was completely effective in controlling the blood pressure of spontaneously hypertensive rats, it only postponed the onset of kidney disease. Enalapril-treated spontaneously hypertensive rats eventually exhibited albuminuria as severe as that found in hypertensive rats. Kidney vessel pathology was completely prevented with enalapril, but the abnormal accumulation of mononuclear cells in tubulointerstitial and periglomerular sites was the same as in untreated spontaneously hypertensive rats. We have concluded that elevated protein excretion in rats of the spontaneously hypertensive rat strain is not a secondary consequence of systemic hypertension. Structural abnormalities of renal vessels also do not appear to contribute significantly to the pathogenesis of albuminuria in spontaneously hypertensive rats. Other explanations must be sought to account for the close link between spontaneous hypertension and kidney damage in this animal model. The clear dissociation of kidney disease from systemic hypertension exhibited by spontaneously hypertensive rats may also be relevant for human disease.
Effects of salt, race, and hypertension on reactivity to stressors.
Authors: Dimsdale J E , Ziegler M , Mills P , Delehanty S G , Berry C
Published: June 2012

Blood pressure and heart rate reactivity to a psychological stressor and to a cold pressor test were examined in a group of 51 normotensive and 37 unmedicated hypertensive men. All were studied twice, once while the participants were maintained on a moderately high salt (200 meq sodium/day) diet and once while the participants were maintained on an extremely low salt (10 meq sodium/day) diet. Dietary salt had no effect on blood pressure or heart rate responses to the two stressors. The systolic and diastolic responses of the white participants to the psychological stressor were greater than those of the black participants (both p less than 0.05); however, there was no difference between blacks and whites in reactivity to the cold pressor challenge. As compared with the normotensive group, the hypertensive group reacted to the psychological stressor with increased responses in systolic blood pressure, diastolic blood pressure, and heart rate (all p less than 0.05). The hypertensive group also hyperresponded in terms of the systolic pressure response to the cold pressor task (p less than 0.05). Plasma norepinephrine and epinephrine responses were not significantly different across the two diets, races, or diagnoses.
Importance of organic osmolytes for osmoregulation by renal medullary cells.
Authors: Garcia-Perez A , Burg M B
Published: June 2012

The cells in the renal medulla protect themselves from the extracellular hypertonicity in that region of the kidney by accumulating large amounts of sorbitol, inositol, glycerophosphorylcholine, and betaine. The system is uniquely active in this part of the body, but it represents a throwback to primitive mechanisms by which cells in virtually all organisms, including bacteria, yeasts, plants, and lower animals counteract water stress. In this brief review, we summarize how these "compatible organic osmolytes" help the renal medullary cells to survive, the mechanisms by which the organic osmolytes are accumulated, and how the accumulation is controlled to adjust for changing extracellular NaCl and urea concentrations. The compatible organic osmolytes are all intermediates in important biochemical pathways, and although the medical consequences are not yet fully worked out, it is already apparent that inappropriate accumulation of these solutes has major pathophysiological consequences.
Psychosomatic factors in borderline hypertensive subjects and offspring of hypertensive parents.
Authors: Perini C , Müller F B , Rauchfleisch U , Battegay R , Hobi V , Bühler F R
Published: June 2012

Psychosomatic factors, sympathoneural and sympathoadrenal as well as cardiovascular mechanisms, were studied in 24 patients 18-24 years of age with borderline hypertension, 50 age-matched normotensive offspring of hypertensive parents, and 49 controls with no family history of hypertension. They were compared by projective and questionnaire-based psychological tests and their circulatory and neurohormonal reactivity to mental (Stroop color-word conflict test and arithmetic test) and physical stressors (orthostasis and bicycle ergometry test) were measured. Borderline hypertensive subjects externalized aggression less (p less than 0.05) but internalized it more (p less than 0.05) and were more submissive (p less than 0.05) when compared with controls. Offspring of hypertensive parents showed a similar but weaker pattern. Both risk groups reported more positive interactions with their parents (genetic risk subjects versus controls, p less than 0.05; borderline hypertensive patients versus controls, p = 0.08) and had higher state-anxiety levels (p less than 0.05). There were more subjective symptoms of beta-adrenergic receptor-mediated functions (e.g., tachycardia, tremor) in borderline hypertensive subjects and offspring of hypertensive parents, elevated heart rates (analysis of repeated measures, p less than 0.001), and enhanced plasma norepinephrine concentrations (p less than 0.05) when compared with controls. These findings in subjects at risk for the development of hypertension suggest that psychosomatic factors and sympathetic overactivity are involved in the early phase of hypertension.
Renal secretion and hepatic clearance of human multiple renin forms.
Authors: Abraham P A , Katz S A , Opsahl J A , Miller R P , Stanchfield W R , Andersen R C
Published: June 2012

Human active renin can be separated into at least five forms by isoelectric focusing. The present study assessed the preferential renal secretion and hepatic degradation of renin forms in humans. The renin form profile of secreted renal renin was determined before transplant in an ex vivo kidney donor perfusion system and compared with the peripheral plasma multiple renin form profile of normal subjects. The effect of hepatic degradation on renin forms was assessed in hepatic vein plasma in comparison with infrarenal vena cava plasma in hypertensive patients during renal vein renin studies. The results revealed a significantly greater proportion of the more basic forms in the perfusate of donor kidneys compared with normal plasma. In hypertensive patients the proportion of the more basic renin forms in the hepatic vein was significantly decreased in comparison with the infrarenal vena cava. Thus, the human kidney may preferentially secrete the more basic renin forms. In contrast, the liver preferentially degrades the more basic forms, giving these forms a shorter plasma half-life. The preferential secretion and clearance of the more basic forms of renin may contribute to short-term control of human renin-angiotensin system activity.
High-normal blood pressure progression to hypertension in the Framingham Heart Study.
Authors: Leitschuh M , Cupples L A , Kannel W , Gagnon D , Chobanian A
Published: June 2012

This study sought to determine if individuals with high-normal blood pressure (diastolic blood pressure of 85-89 mm Hg) progress to hypertension more frequently than those with normal blood pressure (diastolic blood pressure less than 85 mm Hg), thus advancing to a higher cardiovascular risk category. Individuals from the Framingham Heart Study were placed in normal and high-normal blood pressure categories and followed for 26 years for the development of hypertension. With hypertension defined as a diastolic blood pressure of 95 mm Hg or greater or the initiation of antihypertensive therapy, 23.6% of men and 36.2% of women with normal blood pressure developed hypertension compared with 54.2% of men and 60.6% of women with high-normal blood pressure. The relative risk for the development of hypertension associated with high-normal blood pressure was 2.25 for men (95% confidence interval [CI], 1.8-2.8; p less than 0.0001) and 1.89 for women (95% CI, 1.5-2.3; p less than 0.0001). The age-adjusted relative risks estimated by the proportional hazards model were 3.36 for men and 3.37 for women (p less than 0.001). Among those risk factors examined, baseline systolic and diastolic blood pressure, Metropolitan relative weight, and change in weight over time were significant predictors of future hypertension in men and women whose initial blood pressure was normal. For men with high-normal blood pressure, systolic blood pressure and change in weight were identified as risk factors for future hypertension. These results indicate that the probability of individuals with blood pressure in the high-normal range developing hypertension is twofold to threefold higher than in those with normal blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin-(1-7). A member of circulating angiotensin peptides.
Authors: Kohara K , Brosnihan K B , Chappell M C , Khosla M C , Ferrario C M
Published: June 2012

We measured the concentrations of three principal products of the renin-angiotensin system and seven of their metabolites in the plasma of anesthetized normal dogs and in dogs 24 hours after bilateral nephrectomy. The levels of the angiotensin peptides were measured by high-performance liquid chromatography combined with radioimmunoassay using three specific antibodies that recognized different epitotes in the sequences of angiotensin I, angiotensin II, and angiotensin-(1-7). The analysis revealed that angiotensin-(1-7) is present in the plasma of intact (4.9 +/- 2.2 fmol/ml) and nephrectomized (0.5 +/- 0.5 fmol/ml) dogs. An intravenous injection of purified hog renin (0.01 Goldblatt unit/kg) increased plasma levels of angiotensin I, angiotensin II, and angiotensin-(1-7) both before and after nephrectomy. These changes were associated with parallel increases in the concentrations of fragments of the three parent peptides. Administration of MK-422 led to the disappearance of circulating angiotensin II and its fragments both before and after a second injection of the same dose of renin. In contrast, MK-422 augmented the plasma levels of both angiotensin I and angiotensin-(1-7). The concentrations of these two peptides, but not the blood pressure, were again augmented by a second injection of renin given after blockade of converting enzyme. These effects were observed both before and after bilateral nephrectomy. These findings show that angiotensin-(1-7) circulates in the blood of normal and nephrectomized dogs. In addition, we found that angiotensin-(1-7) is generated in the blood from the cleavage of angiotensin I through a pathway independent of converting enzyme (EC 3.4.15.1).