bluuebunny/crossref_metadata_2025 huggingface dataset:
Local renin-angiotensin system in human adrenals and aldosteronomas.
Authors: Sarzani R , Fallo F , Dessì-Fulgheri P , Pistorello M , Lanari A , Paci V M , Mantero F , Rappelli A
Published: June 2012

The local renin-angiotensin system may regulate adrenal cell growth and function. Angiotensinogen, renin, and angiotensin converting enzyme gene expression were studied in four normal adrenal glands (removed from patients with renal carcinomas) and five aldosterone-secreting adenomas. Northern blot analysis showed expression of angiotensinogen messenger RNA (mRNA) in normal adrenals at levels approximately 35-fold lower than liver and sixfold lower than kidney. Similar angiotensinogen mRNA levels were present in two aldosteronomas, whereas a third had levels approximately 50% of those found in kidney. Renin mRNA was detectable in most normal adrenals and in three adenomas, one of which had relatively high renin mRNA levels. Angiotensin converting enzyme gene was expressed in adrenal tissue and in three adenomas. Portions from these normal adrenals and two of these aldosteronomas, as well as samples from two other adrenals and three aldosteronomas, were also studied in an in vitro superfusion system coupled with active renin radioimmunometric assay, angiotensin II/III, and aldosterone radioimmunoassay. Total amounts of active renin and angiotensin II/III released from normal adrenals during 270 minutes of superfusion were higher than the amounts released from aldosteronomas (312 +/- 35 versus 187 +/- 43 and 823 +/- 100 versus 436 +/- 55 pg/100 mg tissue, respectively; mean +/- SEM, p less than 0.05), whereas aldosterone release from the adenomatous tissue was approximately threefold higher (320 +/- 21 versus 115 +/- 18 ng/100 mg tissue; mean +/- SEM, p less than 0.01). Total amounts of active renin and angiotensin II/III released by normal or adenomatous adrenal samples exceeded threefold to fourfold the amounts extracted from similar samples of the same surgical specimen.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of antihypertensive treatment on focal cerebral infarction.
Authors: Fujii K , Weno B L , Baumbach G L , Heistad D D
Published: June 2012

The goal of the current study was to determine whether treatment of hypertension reduces cerebral infarction after occlusion of the middle cerebral artery in stroke-prone spontaneously hypertensive rats (SHRSPs). Three-month-old SHRSPs received untreated drinking water or drinking water containing cilazapril, an angiotensin converting enzyme inhibitor, or hydralazine and hydrochlorothiazide. After 3 months of treatment, the left middle cerebral artery was occluded and neurological deficit was evaluated. Infarct volume was measured 3 days after occlusion using computer imaging techniques from brain slices. Cilazapril and hydralazine with hydrochlorothiazide were equally effective in reducing systolic blood pressure in SHRSPs. One day after occlusion of the middle cerebral artery, neurological deficit was decreased by both cilazapril and hydralazine with hydrochlorothiazide compared with untreated SHRSPs, and the deficit 3 days after occlusion was decreased significantly only by cilazapril. Infarct volume was 178 +/- 7 mm3 (mean +/- SEM) in untreated SHRSPs, and it was significantly reduced to 117 +/- 15 mm3 by hydralazine with hydrochlorothiazide and to 101 +/- 17 mm3 by cilazapril. Infarct volume in Wistar-Kyoto rats was 27 +/- 16 mm3. Thus, reduction in arterial pressure by hydralazine with hydrochlorothiazide or an angiotensin converting enzyme inhibitor is protective against focal cerebral ischemia in SHRSPs.
Atrial natriuretic polypeptide as a novel antigrowth factor of endothelial cells.
Authors: Itoh H , Pratt R E , Ohno M , Dzau V J
Published: June 2012

The migration and proliferation of endothelial cells play a pivotal role in various vascular diseases. We have previously reported that atrial natriuretic polypeptide (ANP) exerts an antigrowth effect on vascular smooth muscle cells via the guanylate cyclase-coupled mechanism. Because the endothelial cells are known to possess a large number of guanylate cyclase-coupled ANP receptors, we examined the action of ANP on the growth of endothelial cells. ANP (10(-7) and 10(-6) M) significantly attenuated serum-stimulated DNA synthesis of cultured bovine aortic endothelial cells with concomitant reduction of the increase in cell number. A ring-deleted analogue of ANP exerted less prominent antiproliferative action, and 8-bromo cyclic GMP (cGMP) mimicked the action of ANP, suggesting the involvement of cGMP cascade in the endothelial growth. Moreover, the proliferative action of exogenously administered basic fibroblast growth factor on endothelial cells was significantly attenuated by the simultaneously administered 8-bromo cGMP. Taken together, the present results demonstrate a potential novel role of ANP in the regulation of endothelial cell growth, which is implicated in angiogenesis or reendothelialization.
Characterization of natriuretic peptide receptors in cultured cells.
Authors: Suga S , Nakao K , Mukoyama M , Arai H , Hosoda K , Ogawa Y , Imura H
Published: June 2012

To elucidate physiological and clinical implications of the natriuretic peptide family, the expression of receptors for natriuretic peptides has been examined in cultured cells (a rat pheochromocytoma cell line [PC12], bovine endothelial cells, rat aortic smooth muscle cells, human mesangial cells, and a porcine kidney epithelial cell line [LLC-PK1]) by Northern blot analysis and cyclic GMP production method for the ANP-A and ANP-B receptors and by Northern blot analysis and binding assay for the clearance receptor. The ANP-A receptor was predominantly expressed in PC12 cells, bovine endothelial cells, and LLC-PK1 cells but was barely expressed in rat aortic smooth muscle cells and human mesangial cells. By contrast, the ANP-B receptor was the major subtype of the biologically active receptors in rat aortic smooth muscle cells and human mesangial cells. Only a small amount of the ANP-B receptor was detected in PC12 cells, bovine endothelial cells, and LLC-PK1 cells. The clearance receptor was abundantly expressed in rat aortic smooth muscle cells and human mesangial cells and was also present in bovine endothelial cells, but it was undetectable in PC12 cells and LLC-PK1 cells. These results demonstrate that the expression of three natriuretic peptide receptors varies from cell to cell, which is relevant to cell- or tissue-specific action of the natriuretic peptide family.
Role of nitric oxide in mediating renal response to volume expansion.
Authors: Alberola A , Pinilla J M , Quesada T , Romero J C , Salom M G , Salazar F J
Published: June 2012

The objective of the present study was to determine the role of endothelium-derived nitric oxide in mediating the renal response to extracellular volume expansion with isotonic saline (5% body weight). In anesthetized dogs (n = 7) and before volume expansion, nitric oxide synthesis was inhibited in the right kidney by continuous intrarenal infusion of NG-nitro-L-arginine-methyl ester (1 microgram/kg/min). Arterial pressure and renal hemodynamics of both kidneys did not change significantly either during nitric oxide synthesis inhibition or during 5% volume expansion. However, in response to extracellular volume expansion, increases in natriuresis, diuresis, and fractional excretion of lithium (an index of proximal sodium reabsorption) were inhibited in the right kidney by 27%, 28%, and 41%, respectively, when compared with the contralateral kidney. Increases of renal interstitial hydrostatic pressure during 5% volume expansion were not statistically different between both kidneys. In another group of dogs (n = 4), the administration of L-arginine (0.5 mg/kg/min) into the right renal artery prevented the renal effects induced by the nitric oxide synthesis inhibitor during volume expansion. The findings in this study suggest that nitric oxide production plays an important role in regulating the renal response to extracellular volume expansion. The proximal tubule seems to be involved in the reduced renal excretory response to volume expansion during nitric oxide synthesis inhibition.
Sympathetic and renin-angiotensin system influence on blood pressure and renal blood flow of two-kidney, one clip Goldblatt hypertensive dog.
Authors: Zimmerman B G , Mommsen C , Kraft E
Published: June 2012

Conscious normotensive and two-kidney, one clip Goldblatt hypertensive dogs were studied to determine the influence of the sympathetic and renin-angiotensin systems on the blood pressure and renal blood flow. Renal blood flow was monitored in a single kidney of the normotensive dogs and in the contralateral kidney of the hypertensive dogs. Saralasin was infused intravenously (i.v.) at 1 microgram/kg/min for 15 minutes in untreated and guanethidine-treated animals. Guanethidine (i.v.) decreased blood pressure (BP) in the hypertensives at X = 16 days after Goldblatt clamp application, but not in the normotensives, and did not affect renal blood flow or vascular resistance in either group. Saralasin produced approximately the same BP decrease in both untreated and guanethidine-treated hypertensives at X = 12 days after Goldblatt clamp application; the combined effect of the drugs was greater than saralasin alone. Blood flow and vascular resistance of the hypertensives' contralateral kidney were not significantly affected by saralasin in these experiments. No sustained effect on BP or renal blood flow was obtained with saralasin in the normotensives. Administration of furosemide was utilized to increase plasma renin activity (PRA) in another series of experiments. In both normotensives and hypertensives, PRA was elevated at 2-3 hours after furosemide application, being greater in the hypertensives. When the renin-angiotensin system was activated in this manner, saralasin had a significant hypotensive and renal vasodilator effect in the hypertensives, but not in the normotensives.
Augmented sympathetic nerve activity and pressor responsiveness in DOCA hypertensive rats.
Authors: Takeda K , Buñag R D
Published: June 2012

Spike potentials in abdominal sympathetic nerves were recorded together with aortic blood pressure before and during electrical stimulation of the posterior hypothalamus in urethane-anesthetized rats. Both the initial rate of sympathetic nerve firing and the subsequent acceleration produced by hypothalamic stimulation were higher in deoxycorticosterone acetate (DOCA) hypertensive than in normotensive rats. Pressor responsiveness was generally augmented, but responses to hypothalamic stimulation, were increased far more than those to injected norepinephrine. Vasodepression produced by blocking autonomic ganglia pharmacologically with pentolinium was also more pronounced in DOCA hypertensive rats than in normotensive controls. These results support the conclusion that a centrally induced sympathetic hyperactivity is important for maintaining the blood pressure elevation in rats with established DOCA hypertension.
Reversibility of arterial and venous changes in renal hypertensive rats.
Authors: Simon G
Published: June 2012

The effect of reversal of hypertension on vascular function and composition was investigated in renal-hypertensive rats. The study comprised three groups of rats: 1) 21 male Sprague-Dawley rats with one-kidney, one clip Goldblatt hypertension of 9 weeks' duration; 2) 20 rats with one-kidney, one clip hypertension that underwent removal of renal artery clip (were "unclipped") at 6 weeks of hypertension, 3 weeks prior to the study; and 3) sham-operated normotensive control rats. Venous pressure-volume and arterial pressure-flow relationships were measured at maximal vasodilation (sodium nitroprusside and papaverine) in the denervated, pump-perfused vascular beds of the hindquarters of rats. Anatomically defined segments of the aorta and of the vena cava were removed from rats for water, sodium, and potassium analysis. Hypertension was completely reversed in the "unclipped" rats. Compared to values obtained in normotensive control rats, the water concentration of the aorta and of the vena cava, the potassium concentration of the aorta, and the sodium concentration of the vena cava were increased (p less than 0.05) in rats with one-kidney, one clip hypertension. These changes were reversed in the "unclipped" rats. In contrast, the shift of the venous pressure-volume and of the arterial pressure-flow curves toward the pressure axis at maximal vasodilation in hypertensive rats (p less than 0.02) persisted following reversal of hypertension in the "unclipped" rats (p less than 0.05). In chronic, one-kidney renovascular hypertension, the contribution of vascular wall "water-logging" to increased structural arterial resistance and decreased structural venous capacity appears to be minor.
An evaluation of the Vita-Stat automatic blood pressure measuring device.
Authors: Polk B F , Rosner B , Feudo R , Vandenburgh M
Published: June 2012

Four Vita-Stat (VS) automatic, coin-operated, blood pressure measuring devices were evaluated for accuracy and precision. Under field conditions, 342 adults had two blood pressure measurements with both the VS device and with the Random-Zero (RZ) device. Two of the VS machines gave significantly higher systolic (SBP) and diastolic blood pressure (DBP) values, compared to the RZ values. The mean difference between these two units and the RZ device were clinically important (14.0 and 6.9 mm Hg SBP; 7.5 and 6.8 mm Hg DBP), and resulted in the misclassification of 23% of normotensives as hypertensives. We observed a significant order effect on SBP with the VS device, with a mean decrement of 4.9 mm Hg between the first and second SBP values, compared to 0.6 mm Hg with the RZ device. Even after adjusting for this bias, all four VS devices gave significantly more variable SBP readings than the RZ unit; two of the four also gave more variable DBP values. These data suggest that the VS device is neither accurate nor precise enough at the present time to be recommended for widespread use. These findings also raise questions concerning the monitoring of performance of this and similar devices in the field.
Determinants of renal vascular resistance in the Dahl strain of genetically hypertensive rat.
Authors: Fink G D , Takeshita A , Mark A L , Brody M J
Published: June 2012

Hypertension-resistant (R) rats of the Dahl strain remain normotensive on diets containing excessive sodium chloride, while hypertension-sensitive (S) rats rapidly become hypertensive when eating the same diet. In the present study, renal hemodynamics were investigated in Dahl rats eating normal or high salt chow for 4 weeks. The R rats eating sodium-enriched chow were found to have significantly lower renal vascular resistance (RVR) than R rats on normal chow; RVR was identical in S rats on either diet. The reason for the failure of S kidneys to exhibit vasodilation during high salt ingestion was explored by examining renal vascular responses to interruption of the renal sympathetic nerves, renal sympathetic nerve stimulation (SNS), and to several vasoactive agents. Changes in RVR to nerve section and to SNS were similar in both strains regardless of diet. Renal vascular responses to intraarterial norepinephrine were suppressed significantly by high salt intake only in the R rats. Changes in RVR to intraarterial angiotensin II were uniformly greater in S than in R rats, but were not altered by salt intake in either strain. Renal vasodilation in response to intraarterial acetylcholine was reduced in R rats on high salt intake, but was not affected by salt intake in S rats. It is concluded that S rats exhibit inappropriately high renal vascular tone during ingestion of excessive salt, and that this alteration is not the result of increased neurogenic activity or increased vascular reactivity to angiotensin II or norepinephrine.
6-keto PGE1: a possible metabolite of prostacyclin having platelet antiaggregatory effects.
Authors: Quilley C P , McGiff J C , Lee W H , Sun F F , Wong P Y
Published: June 2012

Hepatic metabolism of prostacyclin (PGI2) results in the formation of several biologically inactive lipids and one stable product that has the same chromatographic and biological properties as authentic 6-keto PGE1. Both prostaglandins, 6-keto PGE1 and PGI2, have comparable potency in their antiaggregatory and disaggregatory effects on platelets. They contract the superfused rat stomach strip but differ in their effects on the bovine coronary artery, which is contracted by 6-keto PGE1 but relaxed by PGI2. Further, 6-keto PGE1 is considerably more stable than PGI2. Thus, 6-keto PGE1 could account for some of the prolonged effects occasionally seen with PGI2.
Can simple clinical measurements detect patient noncompliance?
Authors: Haynes R B , Taylor D W , Sackett D L , Gibson E S , Bernholz C D , Mukherjee J
Published: June 2012

Measurement of patient compliance is essential if management of low compliance is to be performed efficiently. We assessed the value of several easily obtained clinical assessments compared to quantitative pill counts among 134 newly treated hypertensive male steelworkers during the first 6 months of their treatment with antihypertensive medication. Patient's self-reports obtained on structured interview correlated best with pill count compliance (r = 0.74, p less than 0.0001). Patients overestimated their compliance by an average of 17% but 90% of those who admitted to being noncompliant were found so. Qualitative urinary chlorthalidone and hydrochlorothiazide levels and changes in serum potassium, uric acid, and blood pressure also correlated with pill count compliance but were less accurate than interviews. Assessment of the patient's "health beliefs" and a variety of sociodemographic and health traits and perceptions did not provide useful information on compliance. Interviewing the patient is a simple and useful approach in assessing compliance with antihypertensive therapy.
Oxygen free radicals and cardiac reperfusion abnormalities.
Authors: Goldhaber J I , Weiss J N
Published: June 2012

Oxygen free radicals are highly reactive compounds causing peroxidation of lipids and proteins and are thought to play an important role in the pathogenesis of reperfusion abnormalities including myocardial stunning, irreversible injury, and reperfusion arrhythmias. Free radical accumulation has been measured in ischemic and reperfused myocardium directly using techniques such as electron paramagnetic resonance spectroscopy and tissue chemiluminescence and indirectly using biochemical assays of lipid peroxidation products. Potential sources of free radicals during ischemia and reperfusion have been identified in myocytes, vascular endothelium, and leukocytes. In several different experimental models exogenous free radical-generating systems have been shown to produce alterations in cardiac function that resemble the various reperfusion abnormalities described above. Injury to processes involved in regulation of the intracellular Ca2+ concentration may be a common mechanism underlying both free radical-induced and reperfusion abnormalities. Direct effects of free radicals on each of the known Ca(2+)-regulating mechanisms of the cell as well as the contractile proteins and various ionic membrane currents have been described. Free radicals also inhibit critical enzymes in anaerobic and aerobic metabolic pathways, which may limit the metabolic reserve of reperfused myocardium and contribute to intracellular Ca2+ overload. Inhibiting free radical accumulation during myocardial ischemia/reperfusion with free radical scavengers and inhibitors has been demonstrated to reduce the severity of myocardial stunning, irreversible injury, and reperfusion arrhythmias in many, but not all, studies. This evidence strongly implicates free radical accumulation during myocardial ischemia/reperfusion as an important pathophysiological mechanism of reperfusion abnormalities, although many issues remain unresolved.
Hypertension induces alternatively spliced forms of fibronectin in rat aorta.
Authors: Takasaki I , Chobanian A V , Mamuya W S , Brecher P
Published: June 2012

Fibronectin expression was shown recently to increase in the rat aorta in response to experimental hypertension. Fibronectin is known to alter the phenotype of vascular smooth muscle and endothelial cells, and relative changes in the expression of different isoforms of fibronectin, generated by alternative splicing and distinguished by the absence or presence of inserts designated as EIIIA, EIIIB, and V, may reflect a change in cell phenotype. In the present study we examined the expression of alternatively spliced forms of aortic fibronectin during deoxycorticosterone-salt hypertension. Aortic RNA was analyzed quantitatively using Northern blot analysis and ribonuclease protection assays. Using Northern blot analysis, deoxycorticosterone-salt treatment for 21 days led to a 4.9-fold increase in EIIIA fibronectin messenger RNA, while EIIIB and V forms increased by 2.6- and 2.5-fold, respectively. As determined by ribonuclease protection assays, the percentage of fibronectin transcripts containing either EIIIA, EIIIB, or V in control aorta was 7.3%, 19%, and 40%, respectively. The percentage of EIIIA transcripts increased 42% over control levels after 21 days of deoxycorticosterone-salt treatment, whereas no proportionate change in the other alternatively spliced forms was found. Thus, all forms increased, but a selective increase in the EIIIA form was induced. Analogous increases in each of the fibronectin isoforms were found in the spontaneously hypertensive rats when compared with age-matched Wistar-Kyoto or Wistar rats, and 40-week-old animals showed increases over 10-week-old animals in all strains, consistent with an age-dependent increase in aortic fibronectin expression.
Hypertension and ST segment depression during ambulatory electrocardiographic recording. Results from the prospective population study 'men born in 1914' from Malmö, Sweden.
Authors: Hedblad B , Janzon L
Published: June 2012

The aim of this study in 341 men (aged 68 years) without history of ischemic heart disease was to study the relation between hypertension and silent ischemic-type ST segment depression during ambulatory long-term electrocardiographic recording and to assess the influence between these two variables on cardiovascular morbidity and mortality rates. Seventy-nine men (23%) demonstrated one or more episodes of silent ischemic ST segment depression. One hundred and sixty-seven men (49%) were considered to have hypertension (i.e., they had a diastolic blood pressure of 95 mm Hg or greater or were treated with antihypertensive therapy). Forty-nine (72%) of the 68 treated hypertensive subjects were classified as uncontrolled (i.e., their diastolic blood pressure was 95 mm Hg or greater). The occurrence of ischemic ST depression was higher in hypertensive men (28%) than in normotensive men (19%). The highest incidence of ischemic ST depression (41%) was observed in treated hypertensive men with inadequate blood pressure control. Cardiac event rate during a 53-month follow-up was 6.6% in hypertensive men and 4.6% in normotensive men. Uncontrolled treated hypertensive men had a higher event rate (14%) than hypertensive men overall. Hypertensive men with inadequate blood pressure control and who demonstrated ST segment depression had the highest event rate (25%).
Clustering of cardiovascular risk factors in confirmed prehypertensive individuals.
Authors: Haffner S M , Ferrannini E , Hazuda H P , Stern M P
Published: June 2012

Numerous studies have indicated that hypertensive subjects have an atherogenic lipoprotein pattern, hyperinsulinemia, and impaired glucose tolerance relative to normotensive individuals. These abnormalities could be due to adverse effects of certain antihypertensive agents, to pathophysiological concomitants of the hypertensive state itself, or to both. In this report, we describe the cardiovascular risk factor profile of 1,440 subjects who were normotensive and were not taking any antihypertensive medications when first examined and who subsequently participated in the 8-year follow-up of the San Antonio Heart Study. Hypertension developed in 130 subjects during the follow-up period. At baseline these prehypertensive individuals had significantly higher levels of blood pressure, fasting total and low density lipoprotein cholesterol, triglyceride, glucose, and insulin, and 2-hour glucose than those who remained free of hypertension. In addition, they had higher body mass indexes, a less favorable body fat distribution, and lower levels of high density lipoprotein cholesterol. In multiple linear regression analyses, baseline levels of triglyceride and blood pressure remained significantly higher and high density lipoprotein cholesterol remained significantly lower in the subjects who later converted to hypertension than in those who remained normotensive. Although baseline insulin levels were also higher in the prehypertensive subjects, this difference was not statistically significant. In nonobese subjects, however, those with high baseline insulin concentrations had an increased incidence of hypertension compared with those with low insulin concentrations. The present results suggest that the cluster of atherogenic changes associated with hypertension actually precede the development of the hypertensive state.
Aldosterone enhances angiotensin II receptor binding and inositol phosphate responses.
Authors: Ullian M E , Schelling J R , Linas S L
Published: June 2012

Clinical states in which angiotensin II is increased are often associated with increases in mineralocorticoids. To determine the effects of mineralocorticoids on angiotensin II action, we examined the effects of aldosterone on angiotensin II receptor expression and function in cultured rat vascular smooth muscle cells. Incubation with aldosterone resulted in concentration- and time-dependent increases in angiotensin II receptor number, without changes in binding affinity. For example, incubation with 1 microM aldosterone for 40 hours resulted in 59% increases in angiotensin II receptor number. Increases in angiotensin II receptors were dependent on protein synthesis as evidenced by the time dependency of upregulation and inhibition by cycloheximide. Incubation with aldosterone resulted in enhanced angiotensin II-stimulated phospholipase C activation, as demonstrated by increases in angiotensin II-induced inositol phosphate responses in proportion to the increases in receptor number. In addition, aldosterone prevented angiotensin II-induced downregulation of angiotensin II surface receptors and angiotensin II desensitization of inositol phosphate formation. In summary, aldosterone 1) directly increased angiotensin II receptor number, 2) increased angiotensin II-stimulated inositol phosphate responses, and 3) prevented angiotensin II-induced downregulation and desensitization. In conclusion, aldosterone may potentiate the pressor responses of angiotensin II via effects on angiotensin II receptors.
Hypertension, the endothelial cell, and the vascular complications of diabetes mellitus.
Authors: Hsueh W A , Anderson P W
Published: June 2012

Hypertension is a major factor that contributes to the development of the vascular complications of diabetes mellitus, which primarily include atherosclerosis, nephropathy, and retinopathy. The mechanism of the pathophysiological effects of hypertension lies at the cellular level in the blood vessel wall, which intimately involves the function and interaction of the endothelial and vascular smooth muscle cells. Both hypertension and diabetes mellitus alter endothelial cell structure and function. In large and medium size vessels and in the kidney, endothelial dysfunction leads to enhanced growth and vasoconstriction of vascular smooth muscle cells and mesangial cells, respectively. These changes in the cells of smooth muscle lineage play a key role in the development of both atherosclerosis and glomerulosclerosis. In diabetic retinopathy, damage and altered growth of retinal capillary endothelial cells is the major pathophysiological insult leading to proliferative lesions of the retina. Thus, the endothelium emerges as a key target organ of damage in diabetes mellitus; this damage is enhanced in the presence of hypertension. An overall approach to the understanding and treatment of diabetes mellitus and its complications will be to elucidate the mechanisms of vascular disease and endothelial cell dysfunction that occur in the setting of hypertension and diabetes.
Endothelin-1 augments pressor response to angiotensin II infusion in rats.
Authors: Yoshida K , Yasujima M , Kohzuki M , Kanazawa M , Yoshinaga K , Abe K
Published: June 2012

To assess possible roles of endothelin in the regulation of blood pressure, we studied effects of a subpressor dose of endothelin-1 (3 micrograms/kg/day) on chronic blood pressure responses to infusion of angiotensin II and norepinephrine in rats. Rats were infused with angiotensin II at a subpressor dose (400 micrograms/kg/day i.p.) or with norepinephrine at a subpressor dose (360 micrograms/kg/day i.p.) for 6 days. Systolic blood pressure was significantly elevated during combined infusion of endothelin-1 and angiotensin II, whereas endothelin-1 alone or angiotensin II alone failed to induce any significant changes in systolic blood pressure compared with vehicle alone. This effect was sustained for the whole experimental period and was not associated with any significant changes in body weight, fluid intake, urine volume, or urinary electrolyte excretion. In contrast, combined infusion of endothelin-1 and norepinephrine failed to elevate systolic blood pressure, and no significant difference in systolic blood pressure was observed for the whole experimental period among the four groups of rats with endothelin-1 in combination with norepinephrine, endothelin-1 alone, norepinephrine alone, and vehicle alone. The present results indicate that angiotensin II and endothelin-1, but not norepinephrine and endothelin-1, work synergistically to raise the blood pressure and also suggest the possibility that endothelin-1 may modulate blood pressure control.
Prognostic significance of exercise blood pressure and heart rate in middle-aged men.
Authors: Filipovský J , Ducimetière P , Safar M E
Published: June 2012

Systolic blood pressure and heart rate measured at rest and during a standardized exercise test were analyzed in the cohort of middle-aged male employees followed-up an average of 17 years in the Paris Prospective Study I. The population sample selected for the analysis included 4,907 men who completed at least 5 minutes of bicycle ergometry, who had no heart disease at entry, and whose resting blood pressure was less than or equal to 180/105 mm Hg. Exercise-induced increase in systolic blood pressure was positively correlated with resting systolic blood pressure (r = 0.104, p less than 0.0001), whereas the correlation of exercise-induced heart rate increase with resting heart rate was negative (r = -0.169, p less than 0.001). Using Cox regression analysis with the inclusion of resting systolic blood pressure and heart rate; exercise-induced elevations of systolic blood pressure and heart rate; and controlling for age, smoking, total cholesterol, body mass index, electrical left ventricular hypertrophy, and sports activities, cardiovascular mortality was found to be associated with the systolic blood pressure increase (p less than 0.05), whereas no association with resting systolic blood pressure was found. Total mortality was predicted by resting systolic blood pressure and its elevation (p less than 0.01 for both) and by resting heart rate (p less than 0.0001). The heart rate increase did not contribute to death prediction. In conclusion, the magnitude of the exercise-induced increase of systolic blood pressure, but not of heart rate, may represent a risk factor for death from cardiovascular as well as noncardiovascular causes, independently of resting blood pressure and heart rate.
Renin expression in renal ablation.
Authors: Correa-Rotter R , Hostetter T H , Manivel J C , Rosenberg M E
Published: June 2012

To determine whether expression of the renin-angiotensin system (RAS) is influenced by the degree of renal ablation, male Sprague-Dawley rats underwent uninephrectomy, 1 1/3 nephrectomy, or sham operation. Renin and angiotensinogen messenger RNA (mRNA) were not different among the three groups 2 weeks after surgery. The time course of expression of renin mRNA after 1 1/3 nephrectomy showed no difference versus controls at 2 and 4 weeks and a decrease at 6 weeks after surgical ablation. Because nephrons adjacent to the infarcted area in the 1 1/3 nephrectomy may be hypoperfused and a source of increased renin synthesis, intrarenal distribution of tissue renin content, renin mRNA, and immunostainable renin were examined in separate groups of rats subjected to 1 1/3 nephrectomy. The kidney was divided into two pieces, one containing the scar and scar-adjacent tissue and the other portion the tissue distant from the scar. Tissue renin content, renin mRNA, and immunostainable renin were significantly greater in the scar-adjacent tissue compared with the nonscar tissue. Immunoreactive renin was seen in the juxtaglomerular apparatuses as well as in vascular elements proximal to the juxtaglomerular apparatus and within mesangial cells of some glomeruli of the scar-adjacent tissue. In conclusion, immunostainable renin, tissue renin content, and renin mRNA were increased in scar-adjacent tissue after 1 1/3 nephrectomy. We speculate that this unique scar-associated redistribution of renin may play a pathophysiological role in the progression of renal disease.
Effects of L-arginine on forearm vessels and responses to acetylcholine.
Authors: Imaizumi T , Hirooka Y , Masaki H , Harada S , Momohara M , Tagawa T , Takeshita A
Published: June 2012

This study was designed to investigate the effects of L-arginine (the substrate of endothelium-derived nitric oxide) in human forearm vessels. We examined whether intra-arterial infusion of L-arginine dilated forearm vessels and augmented vasodilatory responses to acetylcholine in young, healthy humans. The left brachial artery was cannulated for drug infusions and direct measurement of arterial pressure. Forearm blood flow was measured by a strain gauge plethysmograph. Intra-arterial infusions of L-arginine at 10, 20, 40, and 60 mg/min increased forearm blood flow from 4.7 +/- 0.6 to 4.9 +/- 0.5, 5.7 +/- 0.5, 7.2 +/- 0.8, and 8.2 +/- 0.9 ml.min-1.100 ml-1, respectively (n = 8, p less than 0.01), whereas D-arginine at the same doses did not alter forearm blood flow (n = 7). Intra-arterial infusions of acetylcholine (n = 7) (4, 8, 16, and 24 micrograms/min) and sodium nitroprusside (n = 5) (0.2, 0.4, 0.8, and 1.2 micrograms/min) increased forearm blood flow dose dependently (p less than 0.01 for both). Arterial pressure was not altered with infusions of these drugs. Responses to acetylcholine were augmented with simultaneous intra-arterial infusion of L-arginine at 10 mg/ml (p less than 0.01) but not with D-arginine. Responses to sodium nitroprusside were not altered by L-arginine. These results in human forearm resistance vessels support the notion that vasodilation induced by acetylcholine is a result of the conversion from L-arginine to endothelium-derived nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)
Association of red blood cell sodium leak with blood pressure in recombinant inbred strains.
Authors: Talib H K , Dobesová Z , Klír P , Kren V , Kunes J , Pravenec M , Zicha J
Published: June 2012

Red blood cell Na+ content as well as ouabain-resistant Na+ and Rb+ (K+) transport (susceptible or resistant to inhibition by loop diuretics) were determined in spontaneously hypertensive rats (SHR) and normotensive Brown Norway (BN) rats the erythrocytes of which were incubated in either saline or Mg(2+)-sucrose medium. Elevated ouabain-resistant Na+ net uptake contrasted with slightly decreased red blood cell Na+ content in SHR compared with BN rats. Acceleration of furosemide- and bumetanide-sensitive Na+ fluxes contributed to enhanced ouabain-resistant Na+ influx into SHR erythrocytes in saline medium, whereas higher furosemide- or bumetanide-resistant Na+ efflux caused greater ouabain-resistant Na+ efflux in Mg(2+)-sucrose medium. Furosemide- and bumetanide-resistant Rb+ leaks were augmented in SHR erythrocytes. The association of the disclosed ion transport alterations with blood pressure was examined in 20 recombinant inbred strains derived from F2 SHR x BN hybrids. Ouabain-resistant Na+ uptake as well as furosemide- and bumetanide-resistant Na+ inward leaks (but not red blood cell Na+ content or furosemide- and bumetanide-sensitive Na+ net uptake) cosegregated with systolic and pulse pressures but not diastolic pressure of the recombinant inbred strains. In contrast, neither ouabain-resistant Na+ efflux nor any component of ouabain-resistant Rb+ uptake correlated positively with blood pressure of the recombinant inbred strains. Increased ouabain-resistant Na+ influx was compensated for by accelerated ouabain-sensitive Na+ extrusion because red blood cell Na+ content was not elevated in the hypertensive strains. Thus, high cell Na+ turnover rates might be related to genetic hypertension if an altered Na+ inward leak would be less effectively compensated for in tissues involved in cardiovascular regulation.
Effects of antihypertensive agents on arterial baroreceptor reflexes in conscious rats.
Authors: Kumagai K , Suzuki H , Ryuzaki M , Kumagai H , Ichikawa M , Jimbo M , Matsumura Y , Saruta T
Published: June 2012

The effects of antihypertensive treatment with four currently used agents (trichlormethiazide, atenolol, nicardipine, and enalapril) on the arterial baroreceptor reflex control of renal sympathetic nerve activity and heart rate were investigated in 45 conscious spontaneously hypertensive rats and 37 age-matched Wistar-Kyoto rats. Antihypertensive agents were administered for 2 weeks beginning at 8 weeks of age to treat and prevent the development of hypertension. Blood pressure was reduced to a similar level (-13 +/- 3 mm Hg, p < 0.05) by each antihypertensive agent. Blood pressure, heart rate, and renal sympathetic nerve activity were recorded in the conscious state during phenylephrine and nitroglycerin ramp infusion. The gain in the baroreceptor reflex was determined from the maximum slope of logistic function curves. Untreated spontaneously hypertensive rats exhibited decreased sensitivity of reflex control of renal sympathetic nerve activity and heart rate (-1.78 +/- 0.07% of control/mm Hg and -2.16 +/- 0.05 beats per minute/mm Hg, respectively) compared with untreated Wistar-Kyoto rats (-3.62 +/- 0.18% of control/mm Hg, p < 0.01, and -3.46 +/- 0.11 beats per minute/mm Hg, p < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Feasibility of ambulatory, continuous 24-hour finger arterial pressure recording.
Authors: Imholz B P , Langewouters G J , van Montfrans G A , Parati G , van Goudoever J , Wesseling K H , Wieling W , Mancia G
Published: June 2012

We tested Portapres, an innovative portable, battery-operated device for the continuous, noninvasive, 24-hour ambulatory measurement of blood pressure in the finger. Portapres is based on Finapres, a stationary device for the measurement of finger arterial pressure. Systems were added to record signals on tape, to alternate measurements between fingers automatically each 30 minutes, and to correct for the hydrostatic height of the hand. We compared the pressure as measured by Portapres with contralateral intrabrachial pressure measured with an Oxford device. Results were obtained in eight volunteers and 16 hypertensive patients. Time lost due to artifact was about 10% for each device. In two patients a full 24-hour Oxford profile was not obtained. In the remaining 22 subjects finger systolic, diastolic, and mean pressures differed +1 (SD 9), -8 (6), and -10 (6) mm Hg, respectively, from intrabrachial pressure. These diastolic and mean pressure underestimations are similar to what was found earlier for Finapres, are typical for the technique, and are systematic. Avoiding brisk hand movements resulted in fewer waveform artifacts. The hand had to be kept covered to continue recording at low outside temperatures. Sleep was not disturbed by Portapres, and arterial pressure showed a marked fall during siesta and nighttime. There were no major limitations in behavior, and no discomfort that originated from continuous monitoring was reported. Measurements continued normally during physical exercise. Portapres provides for the first time continuous 24-hour, noninvasive ambulatory blood pressure waveform monitoring and offers real and obvious advantages over current noninvasive and invasive devices.
Increased endothelin-1 content in blood vessels of deoxycorticosterone acetate-salt hypertensive but not in spontaneously hypertensive rats.
Authors: Larivière R , Thibault G , Schiffrin E L
Published: June 2012

Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced in the endothelium of blood vessels that may play an important role in the control of local blood flow and could be involved in the pathogenesis of hypertension. We investigated immunoreactive ET-1 (ir-ET-1) levels in acid extracts from blood vessels of deoxycorticosterone acetate (DOCA)-salt and spontaneously hypertensive rats. We found that segments of thoracic aorta and the mesenteric vascular bed contain significantly more ir-ET-1 (11.84 +/- 0.84 and 17.30 +/- 1.89 fmol, respectively) than uninephrectomized control rats (1.78 +/- 0.20 and 9.19 +/- 0.63 fmol, respectively; p < 0.001). High performance liquid chromatography showed that ir-ET-1 of blood vessels of DOCA-salt hypertensive rats eluted in the same position as synthetic ET-1. Significantly increased ir-ET-1 was localized by immunohistochemistry in endothelial cells of aorta and large and small mesenteric arteries of DOCA-salt hypertensive rats. In contrast to the latter, in spontaneously hypertensive rats, vascular content of ir-ET-1 was similar to that of blood vessels of Wistar-Kyoto control rats, at both 6 and 16 weeks of age. High levels of vascular ET-1 may explain the downregulation of vascular endothelin receptors previously described in DOCA-salt hypertensive rats. Furthermore, this suggests that ET-1 may be involved in the maintenance of high blood pressure in mineralocorticoid hypertension.
Pressor reactivity to norepinephrine and angiotensin in salt-sensitive hypertensive patients.
Authors: Campese V M , Karubian F , Chervu I , Parise M , Sarkies N , Bigazzi R
Published: June 2012

The mechanisms responsible for increased blood pressure in response to a high dietary sodium intake in salt-sensitive patients with essential hypertension are only partially understood. The possibility that increased reactivity to pressor hormones might contribute to hypertension in these patients has not been adequately investigated. We studied 11 salt-sensitive and 15 salt-resistant patients with essential hypertension while they were ingesting a diet with 20 meq/day sodium for 9 days or one with 200 meq/day sodium for 14 days. During the last 4 days of each dietary regimen, they received 30 mg/day of slow-release nifedipine. Blood pressure response to increasing doses of norepinephrine and angiotensin II (Ang II) was studied at the end of each of four phases of the study. Salt-sensitive patients exhibited a greater blood pressure response to norepinephrine than salt-resistant patients, irrespective of the dietary sodium intake and whether we took into account the dose infused or the actual plasma levels of norepinephrine achieved during the infusion. The blood pressure response to Ang II, on the other hand, was greater in salt-sensitive than salt-resistant patients during low but not during high sodium intake. The blood levels of norepinephrine achieved during the infusion of this hormone were lower in salt-sensitive than in salt-resistant patients. These studies indicate that an increased reactivity to the pressor action of norepinephrine might contribute to the maintenance of hypertension in salt-sensitive patients. The increased reactivity appears to be specific for norepinephrine. In fact, we observed increased reactivity to Ang II during low but not during high sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of weight reduction on cellular cation metabolism and vascular resistance.
Authors: Jacobs D B , Sowers J R , Hmeidan A , Niyogi T , Simpson L , Standley P R
Published: June 2012

The early stages of weight loss are associated with a reduction in blood pressure, and the mechanisms mediating this reduction remain unclear. Platelet free calcium levels, [Ca2+]i, have been reported to be elevated in essential hypertension and to decrease with pharmacological treatment of the hypertension. In the current study, 18 obese subjects had measurements of blood pressure, forearm blood flow, forearm vascular resistance, and both basal platelet [Ca2+]i and [Ca2+]i responses to vasopressin during 12 weeks on a very low calorie (3,360 kJ, or 800 kcal) diet. Weight reduction was associated with reduction in mean arterial blood pressure at 3-4 weeks. There were associated reductions in forearm vascular resistance and platelet [Ca2+]i as well as increases in forearm blood flow at 3-4 weeks of the diet. Increased forearm blood flow was correlated with weight loss. Vasopressin-induced platelet [Ca2+]i responses increased, which correlated with the reduction in mean arterial pressure at 7-8 weeks of weight loss. Assuming that platelet [Ca2+]i metabolism reflects vascular smooth muscle cell [Ca2+]i metabolism, the data suggest that blood pressure reduction after weight loss may be related to reduced vascular smooth muscle cell [Ca2+]i. The reason for the increased vasopressin-induced [Ca2+]i after weight reduction is unclear.
Human lymphocyte sodium-hydrogen exchange. The influences of lipids, membrane fluidity, and insulin.
Authors: Carr P , Taub N A , Watts G F , Poston L
Published: June 2012

The relation between serum lipids, membrane fluidity, insulin, and the activity of the sodium-hydrogen exchanger was investigated in human lymphocytes from 83 subjects. Subjects had a wide range of serum lipids and no concurrent disease. Lymphocyte membrane anisotropy (inversely related to membrane fluidity) was measured with a fluorescence polarization method. Sodium-hydrogen exchange maximal proton efflux rate, affinity for external sodium, and resting pH were determined with the intracellular pH-sensitive fluorochrome 2',5'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Sodium-hydrogen exchange maximal proton efflux rate was negatively correlated with the age of the subject (p = 0.03). Membrane anisotropy correlated with serum triglyceride (p = 0.04). Multiple regression analysis demonstrated that the maximal proton efflux rate in human lymphocytes was significantly related to age (p = 0.005), systolic blood pressure (p = 0.04), membrane anisotropy (p = 0.03), and serum cholesterol (p = 0.03). Incubation of lymphocytes with insulin failed to affect sodium-hydrogen exchange kinetics, intracellular buffering power, or resting intracellular pH. These results suggest that membrane-bound transport proteins may be influenced by serum lipids and the fluidity of the lipid membrane in which they are bound, but they are unlikely to be affected by insulin.