bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin dependence of endothelium-mediated renal hemodynamics.
Authors: Sigmon D H , Carretero O A , Beierwaltes W H
Published: June 2012

Endothelium-derived relaxing factor has been shown to regulate renal blood flow, and inhibition of its synthesis increases blood pressure and renal vascular resistance and decreases renal blood flow. Using the substrate antagonist NW-nitro-L-arginine methyl ester (L-NAME), we tested whether renal vasoconstriction induced by endothelium-derived relaxing factor synthesis inhibition could be mediated in part by angiotensin II. In 14 control rats, 10 mg/kg body wt L-NAME increased blood pressure from 106 +/- 6 to 126 +/- 6 mm Hg (p < 0.001), increased renal vascular resistance by 74% (from 19.3 +/- 2.6 to 33.6 +/- 2.9 resistance units), and decreased renal blood flow by 34% (from 5.9 +/- 0.5 to 3.9 +/- 0.3 ml.min-1.g kidney wt-1, p < 0.005). When six rats were treated with 10 mg/kg body wt of the angiotensin receptor antagonist DuP 753, L-NAME increased blood pressure from 84 +/- 4 to 106 +/- 4 mm Hg (p < 0.001); however, renal vascular resistance increased by only 27% (from 13 +/- 2 to 17 +/- 3 resistance units, p < 0.01; p < 0.05 different from control value) and renal blood flow was unchanged. Likewise, after pretreatment of six rats with 32 micrograms/100 g body wt of the angiotensin converting enzyme inhibitor enalaprilat, L-NAME increased blood pressure from 88 +/- 5 to 124 +/- 6 mm Hg (p < 0.001) and renal vascular resistance by 54% (from 12 +/- 1 to 18 +/- 3 resistance units, p < 0.01; p < 0.05 different from control value) but renal blood flow was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Vasodilators inhibit acute alpha 1-adrenergic receptor-induced trophic responses in the vasculature.
Authors: Thompson K E , Friberg P , Adams M A
Published: June 2012

Cardiovascular hypertrophy plays an important role in the development and maintenance of hypertension. Hyperactivity of the sympathetic nervous system may be one of the initiating factors responsible for the stimulation of growth processes involved in these structural alterations. We have used a well-established early biochemical marker of cellular growth processes, induction of ornithine decarboxylase (ODC), to determine whether alpha 1-adrenergic receptor-induced vascular trophic responses are dependent on arterial pressure elevation. Hydralazine or felodipine were coadministered to control the alpha 1-adrenergic receptor agonist-induced rise in mean arterial pressure (MAP). Methoxamine (2, 5, or 10 mg/kg s.c.) increased the average MAP (up to 20 mm Hg) and vascular ODC activity (up to ninefold) above control rats over 4 hours. Concomitant administration of hydralazine (0.5, 1.25, or 5 mg/kg s.c.) or felodipine (100 or 250 micrograms/kg s.c.) with methoxamine (10 mg/kg) attenuated the alpha 1-adrenergic receptor-induced activation of ODC in the aorta and mesenteric resistance vasculature, as well as the MAP increases. Vasodilators alone did not lower basal vascular ODC activity. The major findings include: 1) alpha 1-adrenergic receptor activation dose-dependently induces vascular ODC activity concomitantly with MAP elevation, 2) vasodilators inhibited both the alpha 1-adrenergic receptor-induced MAP increases and the activation of mesenteric vascular and aortic ODC, and 3) the stimulus-response correlation between MAP elevation and mesenteric (r = 0.78) and aortic (r = 0.92) ODC activation was characterized by a logistic function.(ABSTRACT TRUNCATED AT 250 WORDS)
Level of control of hypertension in Mexican Americans and non-Hispanic whites.
Authors: Haffner S M , Morales P A , Hazuda H P , Stern M P
Published: June 2012

Compared with non-Hispanic whites, Mexican Americans have a higher prevalence of diabetes, greater adiposity, and an unfavorable body fat distribution. The prevalence of hypertension, however, is similar or lower in Mexican Americans than in non-Hispanic whites. There is little information on the level of blood pressure control in Mexican Americans. We compared the mean blood pressure levels of Mexican American and non-Hispanic white hypertensive subjects in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Hypertension was defined as one or more of a systolic blood pressure > or = 160 mm Hg, a diastolic blood pressure > or = 95 mm Hg, and current use of antihypertensive medications. Three hundred and fifty-eight Mexican Americans and 241 non-Hispanic whites met these criteria. Poor hypertension control was defined as a systolic blood pressure > or = 160, a diastolic blood pressure > or = 95 mm Hg, or both. After adjustment for age, gender, obesity, body fat distribution, and level of educational attainment, Mexican American hypertensive subjects were in significantly poorer control than non-Hispanic white hypertensive subjects. The reasons for their poorer control are unknown, but our findings emphasize the importance of hypertension in this ethnic group.
Sustained hypertension induced by orally administered nitro-L-arginine.
Authors: Dananberg J , Sider R S , Grekin R J
Published: June 2012

To study the hemodynamic and metabolic effects of chronic inhibition of endothelium-derived nitric oxide, we treated conscious rats with an oral solution of N omega-nitro-L-arginine (LNA), an inhibitor of nitric oxide production by endothelial cells. After 3 days of treatment with 2.74 mM LNA, rats had higher blood pressures (136 +/- 5 versus 113 +/- 3 mm Hg, p < 0.0005) than did the control animals. This effect was maintained through 7 days of treatment (142 +/- 6 versus 109 +/- 4 mm Hg, p < 0.0005) and in three animals for 35 days (167 +/- 7 mm Hg). The blood pressure rise was dose dependent. The hypertensive effect of oral LNA was not enhanced by the administration of 20 mg intraperitoneal LNA and was prevented by pretreatment with L-arginine, although L-arginine also caused a transient but significant increase in urinary sodium excretion. When LNA treatment was discontinued, blood pressure fell gradually, with an effective biological half-life of 4.2 days. Metabolic balance studies did not identify differences in sodium or potassium balance between treated and control animals. Plasma renin activity was lower in LNA-treated animals, and aldosterone concentrations tended to be lower. In contrast, atrial natriuretic factor levels and serum electrolyte concentrations were unchanged after 7 days of treatment with LNA. These data support the premise that endothelium-derived nitric oxide plays an important role in basal hemodynamic homeostasis. Oral administration of LNA may serve as a model of chronic nitric oxide-deficient hypertension and allow for the future study of endothelium dependence in hypertension.
Reflex vasopressin and renin modulation by cardiac receptors in humans.
Authors: Giannattasio C , Del Bo A , Cattaneo B M , Cuspidi C , Gronda E , Frigerio M , Mangiavacchi M , Marabini M , De Vita C , Grassi G
Published: June 2012

Animal studies have shown that vasopressin secretion is modulated by arterial baroreceptors and cardiopulmonary volume receptors. Whether this is the case also in humans is controversial, however. To determine whether vasopressin is reflexly modulated by cardiac volume receptors, we studied the effect on plasma vasopressin (venous blood, radioimmunoassay) of reducing venous return and left ventricular end-diastolic diameter (echocardiography) by producing a 20-minute lower body negative pressure in 14 healthy subjects (aged 49.3 +/- 3.8 years, mean +/- SEM). The data were compared with those of 14 age-matched heart-transplant recipients, i.e., subjects with cardiac denervation. In healthy subjects, lower body negative pressure at -15 mm Hg caused a modest reduction in left ventricular end-diastolic diameter (-5 +/- 3.4%) and no change in vasopressin, whereas lower body negative pressure at -37.5 mm Hg caused a more marked reduction in left ventricular end-diastolic diameter (-12 +/- 2.5%) and a small, variable, but overall statistically significant (p < 0.05) increase in vasopressin (+145 +/- 46%, p < 0.01). The left ventricular end-diastolic diameter changes induced by the two lower body negative pressure stimuli were similar in heart-transplant recipients, but the vasopressin increase seen with the lower body negative pressure at -37.5 mm Hg was abolished. The marked increase in plasma renin activity and forearm vascular resistance induced by lower body negative pressure in healthy subjects was also abolished or drastically attenuated in heart-transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of nitric oxide and angiotensin II in the regulation of sympathetic nerve activity in spontaneously hypertensive rats.
Authors: Kumagai H , Averill D B , Khosla M C , Ferrario C M
Published: June 2012

This study evaluated the actions of nitric oxide on the blood pressure and renal sympathetic nerve activity responses produced by angiotensin II (Ang II) blockade in conscious spontaneously hypertensive rats. Two days after implantation of electrodes, we measured mean arterial pressure, heart rate, and renal sympathetic nerve activity. Baroreceptor reflex function was assessed with a logistic function curve; the maximum slope of the curve estimated the baroreceptor reflex gain. Data were obtained in rats given acute intravenous administration of either vehicle, the Ang II type 1 receptor antagonist losartan, the type 2 antagonist CGP 42112A, or the converting enzyme inhibitor lisinopril. In comparison with vehicle (-1.1 +/- 0.2%/mm Hg), both losartan (-1.8 +/- 0.3%/mm Hg) and lisinopril (-2.4 +/- 0.2%/mm Hg) significantly increased the maximum gain of the baroreceptor reflex control of nerve activity (p < 0.05). In contrast, the type 2 receptor antagonist did not alter baroreceptor reflex function. Similar studies were performed in rats that received an intravenous injection of NG-monomethyl L-arginine (10 mg/kg). The nitric oxide synthase inhibitor increased baseline blood pressure and decreased renal sympathetic nerve activity. Subsequent administration of losartan or lisinopril returned blood pressure to initial hypertensive level, whereas sympathetic nerve activity was increased to a level above the initial control value. The maximum gain of the baroreceptor reflex control of renal nerve activity was increased after the nitric oxide inhibition. The present study demonstrates that blunted baroreceptor reflex function in conscious spontaneously hypertensive rats is mediated by an Ang II type 1 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Leukocyte-endothelial cell adhesion in spontaneously hypertensive and normotensive rats.
Authors: Arndt H , Smith C W , Granger D N
Published: June 2012

Although the etiology of hypertension-related organ damage remains poorly understood, it has recently been proposed that activated and adherent leukocytes may contribute to the pathogenesis of progressive organ injury in hypertension. The objective of this study was to determine whether the adherence and emigration of leukocytes in microvessels differ between spontaneously hypertensive and normotensive rats. Leukocyte adherence, rolling, and emigration as well as vessel diameter and erythrocyte velocity were monitored in mesenteric venules of age-matched normotensive and hypertensive rats. Measurements were obtained under baseline conditions and during superfusion of the mesentery with either platelet activating factor, leukotriene B4, or NG-nitro-L-arginine-methyl ester, an inhibitor of nitric oxide synthesis. Tissue-associated myeloperoxidase activity, an index of the total tissue granulocyte population, was measured in various tissues of normotensive and hypertensive rats. Systemic arterial pressure and the circulating polymorphonuclear leukocyte count were elevated in hypertensive relative to normotensive rats. The number of adherent and emigrated leukocytes under baseline conditions did not differ between normotensive and hypertensive rats. Although the nitric oxide synthase inhibitor caused a similar rise in leukocyte adherence and emigration in both rat strains, the adhesive interactions elicited by either platelet activating factor or leukotriene B4 were significantly blunted in hypertensive relative to normotensive rats. Flow cytometric analysis of whole-blood samples revealed a lower surface expression of CD11b/CD18 on leukocytes from hypertensive rats under stimulated conditions. Myeloperoxidase activity in mesentery and small and large intestine was low, whereas lung, spleen, and stomach values were high in hypertensive compared with normotensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Elevation of plasma immunoglobulin A in the spontaneously hypertensive rat.
Authors: Chen C M , Schachter D
Published: June 2012

Prior studies describe deficiencies of T-cell-mediated immunity in the spontaneously hypertensive rat (SHR) strain of Okamoto and Aoki. This report describes an alteration of humoral immunity: elevation of the plasma concentration of immunoglobulin (Ig) A and of circulating IgA autoantibodies to single-stranded DNA, double-stranded DNA, and thyroglobulin. The increased plasma IgA levels are evident in prehypertensive SHR, hence not secondary to the hypertension, and they result mainly from increments in polymeric IgA. Plasma IgA content also varied concordantly with the level of systolic blood pressure as influenced by age (older > younger) and gender (male > female) in both the SHR and control Wistar-Kyoto rat strains. Strain differences in plasma IgG or IgM were not observed. Studies of peripheral blood lymphocytes indicate that increased production of IgA is one mechanism for the increment in plasma content. The number of blood lymphocytes capable of producing IgA in vitro in response to the mitogen lipopolysaccharide is increased in SHR. When cultured in the absence or presence of lipopolysaccharide, peripheral blood lymphocytes of SHR secrete more IgA in vitro than do cells of the control strain. No significant strain differences in biliary or renal excretion of IgA were observed. The observed alterations of IgA in the SHR either are causative factors in the development of the hypertension or are the products of an epiphenomenon in which IgA and blood pressure are affected separately, but in parallel, by causative factors related to rat strain, age, and gender.
Role of angiotensin II in high fructose-induced left ventricular hypertrophy in rats.
Authors: Kobayashi R , Nagano M , Nakamura F , Higaki J , Fujioka Y , Ikegami H , Mikami H , Kawaguchi N , Onishi S , Ogihara T
Published: June 2012

Recent studies suggest the linkage of hypertension and insulin resistance. High fructose diet is known to induce hyperinsulinemia and hypertension in rats. In a previous study, however, high fructose (66%) diet failed to elevate blood pressure but increased left ventricular weight in Sprague-Dawley rats. In the present study, we investigated the precise mechanism of high fructose diet-induced changes in the cardiovascular system in rats. Intake of fructose-enriched diet for 2 weeks increased serum insulin and plasma angiotensin II levels. Urinary excretion of sodium and norepinephrine was not changed. Blood pressure measured directly through an indwelling catheter was not increased, but left ventricular weight and protein content were increased by high fructose diet. To further elucidate the role of the renin-angiotensin system, an angiotensin II type 1 receptor antagonist, TCV-116, was given orally at 1 mg/kg per day with either normal or high fructose diet. Concomitant administration of TCV-116 did not affect plasma glucose or serum insulin levels. Plasma angiotensin II was increased, but neither urinary sodium nor norepinephrine was changed by TCV-116. TCV-116 similarly decreased blood pressure in rats on normal and high fructose diets. Increase in left ventricular weight induced by high fructose diet was prevented by the concomitant administration of TCV-116. On the other hand, left ventricular weight in control rats was not changed by TCV-116. In conclusion, increased plasma angiotensin II may account for the left ventricular hypertrophy induced by high fructose diet, whereas hemodynamic change, sodium retention, and the sympathetic nervous system do not play an important role.
Indirect evidence for vascular uptake of circulating renin in hypertensive patients.
Authors: Taddei S , Virdis A , Abdel-Haq B , Giovannetti R , Duranti P , Arena A M , Favilla S , Salvetti A
Published: June 2012

To evaluate whether, in the forearm of hypertensive patients with different circulating renin profiles, local beta-adrenergic receptor-induced production of active renin, plasma renin activity, angiotensin I (Ang I), and angiotensin II (Ang II) was or was not related to the renin profile, we studied four groups of patients: 1) hypertensive patients with primary aldosteronism and suppressed circulating plasma renin activity values (0.15 +/- 0.1 ng Ang I/mL per hour; n = 7), 2) essential hypertensive patients with low (0.47 +/- 0.1 ng Ang I/mL per hour; n = 8) circulating plasma renin activity values, 3) essential hypertensive patients with normal (2.48 +/- 0.52 ng Ang I/mL per hour; n = 8) circulating plasma renin activity value, and 4) renovascular hypertensive patients with high circulating plasma renin activity values (4.16 +/- 2.1 ng Ang I/mL per hour; n = 10). Isoproterenol was infused into the brachial artery, and active renin, plasma renin activity, and Ang I and Ang II forearm balance (venous-arterial differences corrected for forearm blood flow by strain-gauge plethysmography) were measured. Despite a comparable vasodilation, beta-adrenergic stimulation failed to release active renin, plasma renin activity, and Ang I and Ang II in primary aldosteronism. It slightly increased them (except for Ang I) in low renin patients but determined a local production in normal renin and renovascular hypertensive patients. The individual increments in plasma renin activity and Ang II release induced by isoproterenol showed a correlation with the renin profile.(ABSTRACT TRUNCATED AT 250 WORDS)
Novel in vitro gene transfer method for study of local modulators in vascular smooth muscle cells.
Authors: Morishita R , Gibbons G H , Kaneda Y , Ogihara T , Dzau V J
Published: June 2012

Although many in vitro gene transfer methods already exist, such as calcium phosphate precipitation, electroporation, or cationic liposomes, these methods cause significant cell injury and cell death. The study of the biology of endogenous autocrine-paracrine vasoactive systems such as the renin-angiotensin system in vascular cells is limited by the lack of a suitable gene transfer method with high efficiency of transfection and expression that will permit cell biology studies. Recently, the Sendai virus (hemagglutinating virus of Japan, HVJ)-liposome-mediated gene transfer method has been shown to be an efficient and nontoxic method of gene transfer. In this study, we characterized the efficiency and suitability of the HVJ method for vascular biology research. Using SV40 T-antigen complementary DNA (cDNA), we initially compared the efficiency of the HVJ method and lipofection for transfection of cultured vascular smooth muscle cells (VSMCs). We observed that after 35 minutes of incubation, the HVJ method exhibited a 10-fold higher efficiency of transfection than lipofection. We used this method to study vascular angiotensin converting enzyme (ACE) expression in cultured VSMCs and cultured rat carotid arteries in vitro. The HVJ method of transfection of human ACE cDNA into VSMCs and COS cells was significantly more efficient than lipofection. Using this method, we demonstrated that transfection of ACE cDNA resulted in increased DNA synthesis, which was inhibited by the specific angiotensin II receptor antagonist DuP 753 (10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Kinin actions on renal papillary blood flow and sodium excretion.
Authors: Mattson D L , Cowley A W
Published: June 2012

Infusion of bradykinin into the renal medullary interstitium (0.1 micrograms/min, n = 6) significantly increased renal papillary blood flow as measured by laser-Doppler flowmetry to 117 +/- 3% of control without altering cortical blood flow or blood pressure in anesthetized Munich-Wistar rats. In animals prepared for clearance studies, renal medullary bradykinin infusion did not alter total renal blood flow, glomerular filtration rate, or renal interstitial hydrostatic pressure but increased urine flow by 100%, sodium excretion by 111%, and fractional sodium excretion by 107%. No changes occurred in mean arterial pressure or contralateral kidney function during the interstitial bradykinin infusion. Blockade of endogenous kinin degradation by interstitial infusion of captopril (1 mg/hr) significantly increased papillary blood flow by 21 +/- 5% without altering cortical blood flow. Pretreatment with the nitric oxide inhibitor NG-nitro-L-arginine-methyl ester (2 micrograms/min, n = 7) eliminated the increase in papillary blood flow associated with either bradykinin or captopril infusion. We conclude that renal medullary interstitial infusion of bradykinin increases sodium and water excretion, which is associated with a selective increase in papillary blood flow by a nitric oxide-dependent mechanism.
Angiotensin blockade and the progression of renal damage in the spontaneously hypertensive rat.
Authors: Kohara K , Mikami H , Okuda N , Higaki J , Ogihara T
Published: June 2012

The pathophysiological role of angiotensin II in the development of renal sclerosis was investigated in 5/6-nephrectomized, 12-week-old male spontaneously hypertensive rats. After 1 week of a control period, nephrectomized rats received one of the following treatments for 4 weeks: the selective nonpeptide angiotensin II type 1 receptor antagonist TCV-116 (1 mg/kg per day), the angiotensin converting enzyme inhibitor delapril (30 mg/kg per day), hydralazine (15 mg/kg per day), or vehicle. Urinary protein and albumin excretions and systolic blood pressure were determined every week. Rats with reduced renal mass treated with vehicle had a poor survival rate (30%). Although TCV-116, delapril, and hydralazine treatment significantly improved the survival rate for 4 weeks, hydralazine failed to improve proteinuria and albuminuria as well as the decline in renal function compared with delapril or TCV-116. Histological examination revealed that both TCV-116 and delapril protected glomeruli from sclerosis, whereas hydralazine did not improve histological findings (5%, 7%, and 30% of glomeruli were affected, respectively). These results indicate that angiotensin II plays a dominant role through its type 1 receptor in the pathogenesis of renal deterioration by hypertension.
Hypertension in pregnancy.
Authors: Lindheimer M D
Published: June 2012

High blood pressure, which complicates approximately 10% of all pregnancies, remains a major cause of morbidity and mortality for both mother and fetus. A relative paucity of investigative data, as well as the frequent difficulty in making an etiological diagnosis by clinical criteria alone, may be among the reasons why there are many conflicts about the management of hypertension during pregnancy. This clinical conference summarizes current concepts regarding the hypertensive disorders of gestation, focusing on the most dangerous cause, preeclampsia-eclampsia. It further highlights a recent report of the Working Group on High Blood Pressure in Pregnancy convened by the National High Blood Pressure Education Program at the National Heart, Lung, and Blood Institute (the Consensus Report). Among the Working Group's most interesting recommendations in controversial areas were a return to the classification schema suggested by the American College of Obstetricians and Gynecologists in 1972, use of the fifth Korotkoff sound to determine diastolic blood pressure levels, and institution of treatment with antihypertensive drugs for sudden elevations of blood pressure near term to diastolic levels greater than or equal to 105 mm Hg or for levels of 100 mm Hg or higher in pregnant women with chronic hypertension. The Consensus Report further recommended parenteral hydralazine and methyldopa as the drugs of choice for the acute hypertensive crisis and management of chronic hypertension, respectively, based on the long histories of safe use of these agents in gravidas. Parenteral magnesium sulfate remained the preferred therapeutic approach for avoiding or treating the convulsive complication, eclampsia, but the Working Group underscored the need for controlled trials of magnesium's efficacy. Finally, they noted that diuretics should be avoided in preeclampsia, but that these drugs can be continued during gestation if taken before conception, and may be prescribed to pregnant women with chronic hypertension who appear overly salt sensitive.
Longitudinal assessment of blood pressures in black and white children.
Authors: Manatunga A K , Jones J J , Pratt J H
Published: June 2012

The prevalence of hypertension is greater for blacks than whites. Whether black children have higher blood pressure than white children is less clear. We investigated this issue through a prospective longitudinal assessment of blood pressure in 345 white children and 164 black children. Each child had his or her blood pressure measured every 6 months for 2 to 5.5 years. The means for systolic and diastolic blood pressures for each individual were calculated, and the rate of change in blood pressure over time for each subject was estimated. The mean blood pressure and the mean rate were compared between gender-specific black and white groups. For both boys and girls, the mean systolic blood pressure was 2 mm Hg higher in black children than white children (P = .0008). Boys had a higher systolic blood pressure than girls (P = .0048). The mean diastolic blood pressure was 1.5 mm Hg higher in black children than in white children (P = .0270); no significant gender difference in diastolic blood pressure was observed. Age, weight, height, and body mass index were highly correlated with blood pressure. When accounting for these variables, for girls the racial difference in systolic blood pressure remained significant, whereas the difference in diastolic blood pressure in boys and girls was no longer significant. The rate of increase in blood pressure over time was significantly greater in blacks than whites: for systolic blood pressure, P = .0002, and for diastolic blood pressure, P = .009.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of cilazapril on cerebral vasodilatation in hypertensive rats.
Authors: Yang S T , Faraci F M , Heistad D D
Published: June 2012

Endothelium-dependent dilatation of cerebral arterioles is impaired during chronic hypertension. The goal of this study was to determine the effects of an angiotensin converting enzyme inhibitor, cilazapril, on endothelium-dependent dilatation in pial arterioles. Four-month-old Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) received cilazapril in their drinking water (500 mg/L) for 3 to 6 months. Treatment with cilazapril reduced mean arterial pressure in both WKY rats and SHRSP and had no significant effect on baseline diameter of pial arterioles measured with a cranial window. Responses to bradykinin and A23187, but not to nitroglycerin and adenosine, were impaired in SHRSP. Cilazapril did not affect responses to bradykinin (3 x 10(-7) M) and A23187 (10(-5) M) in WKY rats but significantly increased cerebral vasodilatation in response to bradykinin (52 +/- 4% vs 27 +/- 5%) and A23187 (19 +/- 3% vs 8 +/- 3%) in SHRSP. Cilazapril also tended to increase dilator responses to nitroglycerin and adenosine in SHRSP. In another group of SHRSP, treatment with cilazapril for 4 days produced a moderate reduction in blood pressure and increased cerebral vasodilatation in response to bradykinin, A23187, and adenosine. Topical application of the active form of cilazapril (cilazaprilat) for 40 minutes also increased cerebral vasodilatation in response to bradykinin, A23187, and nitroglycerin in SHRSP. The data indicate that an angiotensin converting enzyme inhibitor enhances cerebral vasodilatation in response to endothelium-dependent agonists in SHRSP and may also increase responses to endothelium-independent agonists.
Salt-dependent renal effects of an angiotensin II antagonist in healthy subjects.
Authors: Burnier M , Rutschmann B , Nussberger J , Versaggi J , Shahinfar S , Waeber B , Brunner H R
Published: June 2012

This study was designed to evaluate in healthy volunteers the renal hemodynamic and tubular effects of the orally active angiotensin II receptor antagonist losartan (DuP 753 or MK 954). Losartan or a placebo was administered to 23 subjects maintained on a high-sodium (200 mmol/d) or a low-sodium (50 mmol/d) diet in a randomized, double-blind, crossover study. The two 6-day diet periods were separated by a 5-day washout period. On day 6, the subjects were water loaded, and blood pressure, renal hemodynamics, and urinary electrolyte excretion were measured for 6 hours after a single 100-mg oral dose of losartan (n = 16) or placebo (n = 7). Losartan induced no significant changes in blood pressure, glomerular filtration rate, or renal blood flow in these water-loaded subjects, whatever the sodium diet. In subjects on a low-salt diet, losartan markedly increased urinary sodium excretion from 115 +/- 9 to 207 +/- 21 mumol/min (P < .05). The fractional excretion of endogenous lithium was unchanged, suggesting no effect of losartan on the early proximal tubule in our experimental conditions. Losartan also increased urine flow rate (from 10.5 +/- 0.4 to 13.1 +/- 0.6 mL/min, P < .05); urinary potassium excretion (from 117 +/- 6.9 to 155 +/- 11 mumol/min); and the excretion of chloride, magnesium, calcium, and phosphate. In subjects on a high-salt diet, similar effects of losartan were observed, but the changes induced by the angiotensin II antagonist did not reach statistical significance. In addition, losartan demonstrated significant uricosuric properties with both sodium diets.(ABSTRACT TRUNCATED AT 250 WORDS)
Elevated renovascular tone in young spontaneously hypertensive rats. Role of cytochrome P-450.
Authors: Imig J D , Falck J R , Gebremedhin D , Harder D R , Roman R J
Published: June 2012

The present study examined the role of cytochrome P-450 metabolites of arachidonic acid in elevating renal vascular resistance in young spontaneously hypertensive rats (SHR). Differences in vascular tone were assessed in the preglomerular vasculature of 3- to 4-week-old prehypertensive SHR (n = 11) and normotensive Wistar-Kyoto (WKY, n = 10) and Wistar-Lewis (n = 10) rats. Pressure-diameter relations to changes in renal perfusion pressure were compared using the juxtamedullary nephron microvascular preparation perfused in vitro with a physiological salt solution. At a pressure of 60 mm Hg, the basal diameters of the interlobular arteries and proximal and distal afferent arterioles of the SHR averaged 43 +/- 2, 17 +/- 0.3, and 11 +/- 0.4 microns, respectively. The diameters of the interlobular arteries and afferent arterioles were 9% to 14% smaller than those of corresponding vessels in WKY and Wistar-Lewis rats. Addition of P-450 inhibitors, ketoconazole (100 mumol/L) or 7-ethoxyresorufin (1 mumol/L), to the perfusate dilated the afferent arteriole of SHR by 7% to 12%, whereas it increased the diameter by only 0% to 6% in control rats and significantly reduced the differences in the pressure-diameter relation in the preglomerular vasculature of SHR and control rats. Inhibitors of P-450 eliminated the contractile response of afferent arterioles to increases in renal perfusion pressure in all three groups. Removal of calcium from the perfusate eliminated differences in the diameters of the preglomerular vasculature in SHR and normotensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of calcium channel blockade on the aortic intima in spontaneously hypertensive rats.
Authors: Gray G A , Clozel M , Clozel J P , Baumgartner H R
Published: June 2012

Hypertension is associated with an intimal dysfunction characterized by endothelium-dependent constriction to serotonin, decreased endothelium-dependent relaxation to acetylcholine, and a subendothelial infiltration of monocyte-macrophages. The goal of our study was to evaluate the effect of long-term calcium channel blockade with Ro 40-5967, a new long-acting calcium channel blocker, on these alterations in aortas of spontaneously hypertensive rats (SHR). Arterial blood pressure was decreased by Ro 40-5967. In aortas from Ro 40-5967-treated SHR, the serotonin ratio (maximal contraction to serotonin on rings with endothelium over maximal contraction on paired rings without endothelium) was reduced (1.14 +/- 0.10) compared with control SHR (1.72 +/- 0.12, P < .01) because of inhibition of maximal contraction in rings with endothelium. This effect of Ro 40-5967 was partially reversed by an inhibitor of nitric oxide (NO) synthase, NG-nitro-L-arginine-methyl ester, and partially inhibited in the presence of the thromboxane/prostaglandin H2 receptor antagonist AH 23848. Maximal relaxation to acetylcholine in rings with endothelium was increased by Ro 40-5967. In rings without endothelium, Ro 40-5967 treatment enhanced the sensitivity to sodium nitroprusside-induced relaxation. Cyclic GMP content, an indicator of NO release, was not increased in aortas from Ro 40-5967-treated SHR. Thus, improvement of endothelial function was probably achieved by facilitating the action of NO at the level of the smooth muscle cells and by reducing prostaglandin H2-induced constriction. Finally, the number of monocyte-macrophages in the subendothelium was decreased by Ro 40-5967. 40-5967.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac adenylyl cyclase, beta-adrenergic receptors, and G proteins in salt-sensitive hypertension.
Authors: Böhm M , Gierschik P , Knorr A , Schmidt U , Weismann K , Erdmann E
Published: June 2012

The present study investigated whether high salt intake (8%) in Dahl salt-sensitive and salt-resistant rats with and without hypertension produces a heterologous desensitization of cardiac adenylyl cyclase as observed in various types of hypertension and human heart failure. In membranes from Dahl salt-sensitive rats on a high-salt diet (8%) basal, isoproterenol-, 5'-guanylylimidodiphosphate-, and forskolin-stimulated adenylyl cyclase was reduced compared with the low-salt (0.4%) group and Dahl salt-resistant rats on either 0.4% or 8% sodium chloride. The activity of the catalyst was depressed, and the expression of the immunodetectable inhibitory G proteins Gi alpha was increased in Dahl salt-sensitive rats on 8% sodium chloride, whereas the density of beta-adrenergic receptors and the activity of the stimulatory G protein Gs alpha reconstituted into Gs alpha-deficient S49 cyc- mouse lymphoma cell membranes were unchanged in any condition studied. We conclude that high salt intake in salt-sensitive hypertensive Dahl rats produces hypertension, cardiac hypertrophy, and heterologous desensitization of cardiac adenylyl cyclase. The latter alteration is due to an increase of Gi alpha proteins and a depressed catalyst activity of adenylyl cyclase. The results demonstrate that heterologous adenylyl cyclase desensitization can precede the development of contractile dysfunction in later stages and can occur independently of changes in beta-adrenergic receptors.
'White coat' hypertension. No harm for the heart.
Authors: Gosse P , Promax H , Durandet P , Clementy J
Published: June 2012

The superiority of ambulatory blood pressure monitoring over casual blood pressure measurement for the prediction of target-organ damage is now well established, although the significance of "white coat" hypertension is still controversial. Is an office blood pressure measurement that is higher than the mean ambulatory value an added risk? Because left ventricular hypertrophy is a potent risk factor, the effect of hypertension on left ventricular mass merits attention. Left ventricular mass indexed for height was measured by M-mode echocardiography in 204 essential hypertensive patients (140 males, 64 females; mean age [SD], 50 [11] years). Blood pressure over 24 hours was monitored routinely with a noninvasive auscultatory device. Office blood pressure after 10 minutes of the subject in the supine position was measured by the same physician under the same conditions. The white coat effect was defined as the difference between the office and average daytime values of systolic and diastolic blood pressures. Patients were divided into four quartiles according to their office and daytime blood pressures. Two-way analysis of variance was used to assess the influence of the white coat effect at a given level of daytime blood pressure on left ventricular mass. Left ventricular mass increased significantly (P < .001) with daytime systolic blood pressure but was independent of white coat effect for both the whole population and the 143 untreated patients. We conclude that the white coat effect has no influence on left ventricular mass, favoring the view that white coat hypertension is a benign condition.
Is white coat hypertension innocent? Structure and function of the heart in the elderly.
Authors: Kuwajima I , Suzuki Y , Fujisawa A , Kuramoto K
Published: June 2012

To evaluate the morphological and functional characteristics of the heart in elderly patients with white coat hypertension, we performed an echocardiographic study in 67 elderly individuals older than 60 years: 17 patients with white coat hypertension, 34 patients with true hypertension, and 16 normotensive control subjects. White coat hypertension was defined as a mean 24-hour ambulatory systolic blood pressure of less than 140 mm Hg associated with office hypertension. Cardiac responses to an isometric handgrip exercise test were used to evaluate left ventricular functional reserve. Left atrial dimension and left ventricular mass index were significantly greater in the white coat hypertension group than in the normotension group (P < .05) but were similar to values in the true hypertension group. Left ventricular diastolic function, expressed by peak late-early filling ratio of diastolic mitral flow, showed increasing impairment in the order of the normotension, white coat hypertension, and true hypertension groups (analysis of variance, P < .05); the ratio in the white coat hypertension group tended to be higher than that in the normotension group (unpaired t test, P = .054). The relation between fractional shortening and end-systolic stress did not shift downward after handgrip exercise in the white coat hypertension group, indicating that functional reserve in the left ventricle was maintained. Thus, patients with white coat hypertension had a moderately increased left atrial dimension and left ventricular mass in association with a tendency for disturbed diastolic function, although systolic functional reserve remained the same. These findings suggest that white coat hypertension in the elderly may not be innocent.
Rapid modulation of renal and adrenal responsiveness to angiotensin II.
Authors: Conlin P R , Moore T J , Williams G H , Hollenberg N K
Published: June 2012

Reciprocal changes in adrenal and vascular responsiveness to angiotensin II (Ang II) are part of the normal adaptation to shifts in salt intake. When dietary salt intake is abruptly reduced from high to low, enhancement in aldosterone secretion requires several days to develop. Once established it is not known how quickly the enhancement is reversed with salt repletion. We investigated the time course and relative contributions of salt, volume expansion, or both to this process by studying 15 normotensive subjects; 5 were studied during both high-salt and low-salt balance, and 10 were studied only in low-salt balance. For rapid volume expansion to reverse low-salt balance, 5 subjects received in random order an infusion of normal saline or dextran. The adrenal glomerulosa and renal vascular responses to Ang II were assessed after each volume expansion maneuver. Saline and dextran infusions suppressed plasma renin activity and aldosterone equally, although dextran acted more slowly. Both also increased renal perfusion and renal vascular and pressor responses to Ang II, which in 3 to 7 hours became identical to responses seen during high-salt intake ("modulation"). Saline infusion also blunted adrenal responsiveness to Ang II during that same interval. Despite suppression of the renin-angiotensin system by dextran infusion, aldosterone responsiveness to Ang II remained enhanced. These observations suggest that the renal and vascular responses to Ang II are modulated rapidly by the effects of volume expansion per se.(ABSTRACT TRUNCATED AT 250 WORDS)
L-arginine administration normalizes pressure natriuresis in hypertensive Dahl rats.
Authors: Patel A , Layne S , Watts D , Kirchner K A
Published: June 2012

A blunted pressure-natriuretic response characterizes hypertension in the Dahl salt-sensitive rat. Long-term L-arginine administration prevents hypertension in these animals. To determine if long-term L-arginine corrects the pressure-natriuretic response, we gave salt-sensitive rats on an 8% sodium diet L-arginine or vehicle daily for 3 weeks. Identically treated salt-resistant rats served as controls. After 3 weeks, acute pressure-natriuresis curves were determined. To control for hypertension-induced renal damage, we also examined pressure natriuresis in salt-sensitive rats after short-term L-arginine. Baseline mean arterial pressure was 158 +/- 3 mm Hg in vehicle-treated salt-sensitive rats and 127 +/- 3 mm Hg in chronically L-arginine-treated salt-sensitive rats. During alterations in perfusion pressure, renal blood flow was autoregulated in all groups. Glomerular filtration rate was autoregulated in salt-resistant rats and L-arginine-treated salt-sensitive rats but fell with decreasing pressure in vehicle-treated salt-sensitive rats. Sodium excretion was greater (P < .05) in L-arginine-treated than in vehicle-treated salt-sensitive rats and did not differ from salt-resistant rats at 100, 125, and 158 mm Hg. The slope of the pressure-natriuresis relation was greater (P < .05) in chronically L-arginine-treated than in vehicle-treated salt-sensitive rats. L-Arginine had no effect on natriuresis in salt-resistant rats. Thus, long-term L-arginine administration normalizes pressure-natriuretic responses in salt-sensitive rats. The effect is not due to the prevention of renal damage and is specific to the salt-sensitive strain.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension in the spontaneously hypertensive rat and the sex chromosomes.
Authors: Vincent M , Kaiser M A , Orea V , Lodwick D , Samani N J
Published: June 2012

We investigated the involvement of loci on the sex chromosomes in the hypertension of the spontaneously hypertensive rat (SHR) by studying male F1 and F2 generation rats derived from reciprocal crosses of SHR with Wistar-Kyoto (WKY) rats (cross 1: WKY female x SHR male; cross 2: SHR female x WKY male). At 16 weeks of age there was no significant difference in the blood pressures of F1 animals derived from the two crosses. Similarly, in the F2 generation there was no significant difference in either indirect blood pressures measured at 12, 16, or 20 weeks of age or in direct systolic and diastolic blood pressures measured at 25 weeks of age between animals derived from the two crosses maintained on a normal salt diet. In a second study, cohorts of F2 rats from the two crosses were given 1% salt in their drinking water for 10 weeks from 16 weeks of age with indirect blood pressure measurements at 16 (presalt), 18, and 20 weeks and direct blood pressure measurements at 26 weeks. Although overall these animals had significantly higher blood pressures at both 20 and 26 weeks than animals of the first study, again there was no difference in blood pressures of animals derived from the two crosses, apart from a marginally significantly higher blood pressure at 18 weeks in animals from cross 1 (with SHR grandfather). The findings indicate that the sex chromosomes of the SHR and WKY rat used in these crosses do not contain loci where alleles differentially influence blood pressure under the genetic milieu provided by the cross.(ABSTRACT TRUNCATED AT 250 WORDS)
Twenty-four-hour blood pressure and heart rate profiles in humans. A twin study.
Authors: Degaute J P , Van Cauter E , van de Borne P , Linkowski P
Published: June 2012

To delineate the relative roles of genetic and environmental factors on physiological variations of blood pressure and heart rate, we performed 24-hour ambulatory blood pressure monitorings with simultaneous polygraphic sleep recordings in 28 monozygotic and 16 dizygotic healthy young male twin pairs investigated in a standardized physical and social environment. Blood pressure and heart rate were measured every 10 minutes for 24 hours. A best-fit curve based on the periodogram method was used to quantify changes in blood pressure and heart rate over the 24-hour span. Surprisingly, monozygotic twins as a group tended to have higher blood pressure values than dizygotic twins, and this difference reached the level of significance for daytime systolic blood pressure (P < .005). Although environmental influences largely controlled the mean levels and characteristics of the 24-hour systolic blood pressure variations, significant genetic effects were demonstrated for the mean levels and 24-hour patterns of diastolic blood pressure and heart rate. For both diastolic blood pressure and heart rate, the genetic effects concerned largely the same characteristics of the 24-hour profiles: the 24-hour mean, the daytime mean, the value of the evening acrophase, and the value of the major acrophase. Moreover, there was a strong genetic influence for the amplitude of the 24-hour rhythm of heart rate.
Accelerated decline in renal perfusion with aging in essential hypertension.
Authors: Schmieder R E , Schächinger H , Messerli F H
Published: June 2012

The present cross-sectional study was designed to assess the effect of the severity of hypertensive cardiovascular disease and age on renal hemodynamics. In a homogeneous population of 157 white men (aged 15 to 87 years), we assessed renal and systemic hemodynamics by measuring mean arterial pressure invasively, renal blood flow by 131I-para-aminohippuric acid clearance, and cardiac output by the indocyanine dye dilution technique. Stepwise multiple regression analysis revealed the following independent determinants of renal blood flow: age (beta = -.42, P < .001), height (beta = +.14, P < .03), mean arterial pressure (beta = -.15, P < .02), and cardiac output (beta = +.19, P < .008). Renal blood flow corrected for height correlated inversely with age in all three groups. However, the renal fraction of cardiac output did not correlate with age in borderline hypertension (r = .17, P = NS) and in normotension (r = .12, P = NS), suggesting a parallel decline in renal blood flow and cardiac output with aging. In contrast, in established hypertension, the renal fraction of cardiac output was closely linked to age (r = .52, P < .001) and significantly steeper (P < .01) than in normotension or borderline hypertension. We conclude that unlike in normotensive subjects or patients with borderline hypertension, patients with established hypertension have an accelerated decline in renal perfusion with aging, reflecting selective functional or structural changes or both in the renal vascular bed.