bluuebunny/crossref_metadata_2025 huggingface dataset:
Caffeine may potentiate adrenocortical stress responses in hypertension-prone men.
Authors: Lovallo W R , Pincomb G A , Sung B H , Passey R B , Sausen K P , Wilson M F
Published: June 2012

The effect of caffeine on blood cortisol levels and blood pressures was examined during rest and in response to a challenging psychomotor task in men with a low versus high risk of essential hypertension. Thirty-four healthy men ages 21-35 years were selected such that 17 were at high risk for hypertension (positive parental history and screening blood pressures of 135/85-155/95 mm Hg) and 17 were at low risk (negative parental history and no pressures above 132/84 mm Hg). Testing consisted of quiet rest (20 minutes); oral placebo (grapefruit juice) or caffeine administration (3.3 mg/kg in grapefruit juice); rest during a postdrug absorption period (40 minutes); work on an unsignalled simple reaction time task (15 minutes); and quiet rest (20 minutes). Blood pressures were recorded at 2-minute intervals, and blood samples were withdrawn via an indwelling catheter at the end of the baseline, drug absorption, task, and recovery periods. The combination of task plus caffeine produced the highest blood pressures in men at risk for hypertension. Cortisol levels were found to be sustained during rest in members of the high risk group after they had consumed caffeine, whereas members of the low risk group showed a modest decline. The high risk subjects also showed a significant rise in cortisol during (+3.7 micrograms/dl) and after (+4.0 micrograms/dl) work on the reaction time task after caffeine consumption.(ABSTRACT TRUNCATED AT 250 WORDS)
Smoking accounts for adverse effect of antihypertensive medications on plasma lipids. A population-based study.
Authors: Halkin H , Or J , Fuchs Z , Lusky A , Chetrit A , Modan M
Published: June 2012

Mean plasma levels of total cholesterol, high density lipoprotein cholesterol, total-to-high density lipoprotein cholesterol ratio, and total triglycerides were determined in a representative sample of the adult Israeli Jewish population, excluding known diabetics and individuals with overt atherosclerotic morbidity (n = 1,153). Levels were compared in normotensive and untreated and treated hypertensive individuals by glucose tolerance category and smoking, after adjustment for sex, age, and body mass index. In the presence of normal glucose tolerance, lipid levels in the nonsmoking normotensive and treated hypertensive groups were similar, whereas in the smoking, treated hypertensive group, lipids were significantly affected, as indicated by the respective adjusted mean levels (mg/dl): total cholesterol, 219, 221, and 240; high density lipoprotein cholesterol, 45.0, 43.6, and 42.0; ratio, 5.2, 5.3, and 6.0; and triglycerides, 114, 107, and 144. In individuals with glucose intolerance, trends were the same with the exception of triglycerides, which were significantly elevated in the nonsmoking, treated hypertensive group also; the respective values were 217, 225, and 257 for total cholesterol; 45.1, 44.9, and 41.4 for high density lipoprotein cholesterol; 5.2, 5.5, and 6.8 for the ratio; and 133, 152, and 187 for triglycerides. Lipid disturbances in treated smokers were not due to heavier smoking or differences in dietary intake. We conclude that disturbance of plasma lipid profile in treated hypertensive individuals may be mainly due to an interaction with smoking, with an additional effect of glucose intolerance.
Prospective analysis of strategies for diagnosing renovascular hypertension.
Authors: Svetkey L P , Himmelstein S I , Dunnick N R , Wilkinson R H , Bollinger R R , McCann R L , Beytas E M , Klotman P E
Published: June 2012

Renovascular hypertension is a potentially curable form of high blood pressure. However, it is unclear how best to select patients who are likely to have renovascular hypertension, what diagnostic strategy to use in these selected patients, and how to predict the hemodynamic significance of a renal artery stenosis. We determined the prevalence of renovascular hypertension in adults who exhibited suggestive clinical features. In these clinically selected patients, we then determined the test characteristics of various diagnostic and potential screening tests. Renovascular hypertension was diagnosed if correction of renal artery stenosis resulted in decreased blood pressure. Of the 66 hypertensive adults evaluated, 11 (16.7%) had renovascular hypertension. Captopril-stimulated peripheral renin activity detected renovascular hypertension with 73% sensitivity, 72% specificity, 38% positive predictive value, and 92% negative predictive value. Less optimal combinations of sensitivity and specificity were found for differential glomerular filtration rate renography, differential effective renal plasma flow renography, and selective renal vein renin ratios, each performed after a single dose of captopril. Intravenous digital subtraction renal angiography detected all patients with renovascular hypertension and was normal in 71% of patients with essential hypertension. To evaluate potential screening tests for renovascular hypertension, we calculated predictive values applied to a low prevalence population. If the observed sensitivities and specificities apply to a population with 5% prevalence of renovascular hypertension, captopril-stimulated peripheral renin would have a positive predictive value of 12% and a negative predictive value of 98%. In 16 patients with known renal artery stenosis, neither the captopril-stimulated renal vein renin ratio nor captopril-stimulated differential renography accurately predicted blood pressure response to correction of the stenosis. We conclude that clinical criteria can identify a subgroup with 16.7% prevalence of renovascular hypertension. In this high prevalence group, intravenous digital subtraction renal angiography will identify virtually all patients with renovascular hypertension, and a normal study will be sufficient to exclude renovascular hypertension. In unselected hypertensive patients, screening with captopril-stimulated peripheral renin activity may be the most useful and efficient procedure for identification of patients with renovascular hypertension. Functional tests do not accurately predict the hemodynamic significance of a renal artery stenosis.
Defective protein phosphorylation associated with hypofunctions in stroke-prone spontaneously hypertensive rat platelets.
Authors: Tomita T , Ikeda M , Inoue Y , Mitubori T , Umegaki K
Published: June 2012

The mechanism of platelet dysfunctions in stroke-prone spontaneously hypertensive rats (SHRSP) was investigated. Platelet aggregation was inversely correlated with blood pressure or heart weight/body weight ratios in various strains of spontaneously hypertensive rats (SHR), indicating genetic defects. Thrombin-induced 47 kDa protein phosphorylation was markedly reduced in platelets of SHRSP compared with that in Wistar-Kyoto (WKY) rat platelets, accompanying reduced aggregation and secretion, but in 20 kDa protein phosphorylation was unchanged. Ca2+ ionophore A23187-induced responses were also significantly decreased in SHRSP, and the degrees of the changes were greater than those by thrombin. However, 12-O-tetradecanoylphorbol 13-acetate-induced responses in SHRSP were similar to those in WKY rats, suggesting that protein kinase C activity and its substrate were normally present in SHRSP platelets. Phosphatidylinositol content in platelets of SHRSP was 20% less than that in WKY rat platelets, but the contents of other phospholipids, including phosphatidylinositol-4-monophosphate and phosphatidylinositol-4,5-bisphosphates, were unaltered. Thrombin-induced formation of diacylglycerols and phosphatidic acid did not differ from each other at the low concentrations. In the absence of Ca2+, thrombin-induced responses occurred to a similar degree in both platelets, whereas the enhancements by Ca2+ were much greater in WKY rats than in SHRSP. These results suggested that defective Ca2+ functions in receptor-mediated activation of protein kinase C and postkinase-mediated events appear to be an underlying mechanism for the hypofunctions in SHRSP platelets.
Aortic hypertrophy and "waterlogging" in the development of coarctation hypertension.
Authors: Overbeck H W , Magargal W W
Published: June 2012

To study the mechanisms and roles of vascular structural changes during the development of hypertension, we coarcted or sham-coarcted the abdominal aorta of rats. At intervals of 3 to 56 days later, we obtained standardized segments of thoracic and abdominal aortas for measurement of dry weight, water content, and amino acid content. Carotid arterial pressure was elevated by day 5 in coarcted rats and remained elevated. Femoral and tail arterial pressures remained normal. Cardiac ventricular weight and dry weight of the thoracic aorta, normalized for body weight, rose rapidly over 3-10 days in coarcted rats, remaining constant at 50-60% above levels in sham-coarcted rats thereafter. In contrast, water content of thoracic aorta in coarcted rats peaked at 123% of control values on day 7 (p less than 0.001), falling rapidly thereafter to levels about half of peak. Increments in dry weight and water content of the normotensive abdominal aortic segments were of far lesser magnitude and occurred 1 to 2 weeks later, probably reflecting the effects of initial hypotension of the hindquarters. Percent hydroxyproline of intima-media segments of the thoracic aorta remained normal during the 8-week period, indicating that increases in aortic dry weight did not represent disproportional fibrosis and thus are attributable to muscular hypertrophy. These results provide support for the hypothesis that arterial wall "waterlogging" is primarily an early manifestation of the hypertensive process. The greatest magnitude of waterlogging coincides with the rapid early increase in aortic dry weight, representing hypertrophy, which suggests common mechanisms, such as activation of Na+-H+ antiport.
Mechanisms of suppression of renal kallikrein activity in low renin essential hypertension and renoparenchymal hypertension.
Authors: Shimamoto K , Masuda A , Ando T , Ura N , Nakagawa M , Mori Y , Nakagawa H , Sakakibara T , Ogata H , Iimura O
Published: June 2012

The mechanism of suppression of renal kallikrein activity in low renin essential hypertensive and renoparenchymal hypertensive patients was investigated in this study. From Sephadex G-200 column chromatography studies, a single kallikrein peak was observed in both kallikrein radioimmunoassay and kininogenase activity in all samples from normal subjects, low renin essential hypertensive and renoparenchymal hypertensive patients, and in purified kallikrein solution. The enzyme-specific activity around the kallikrein peak in all urine samples from each group was significantly lower than that in purified kallikrein, and a significantly lower specific activity was found in both patient groups than was found in normal subjects. Moreover, it was also recognized that the specific activity of kallikrein decreased in all cases with the increase of the molecular weight of kallikrein, and this tendency was observed more obviously in the low renin essential hypertensive and renoparenchymal hypertensive patients than in the normal subjects. These results suggest the presence of a kallikrein-specific inhibitor with a low molecular weight in human urine, although the possibility of a variant form of kallikrein cannot be excluded.
Effect of converting enzyme inhibition on renin synthesis and secretion in mice.
Authors: Barrett G L , Morgan T O , Smith M , Alcorn D , Aldred P
Published: June 2012

We have investigated the relative importance of renal renin stores and de novo synthesis during stimulation of renin secretion and the role of transcription and posttranscriptional factors in providing increased synthesis of renin. When enalapril was administered to previously untreated mice, plasma renin concentration increased 40-fold within 1.5 hours, and remained at a high level for the 8 days of the experiment. Renal renin decreased by 82% after 24 hours and thereafter increased to levels higher than controls. Calculations of renin turnover, based on data for the rate of metabolism of renin in plasma, indicated that most of the renin released in the first 24 hours could be accounted for by the decrease in renal renin stores, indicating that de novo synthesis played only a minor role. After 24 hours, however, when both plasma renin concentration and renal renin increased, the calculated rate of renin synthesis increased to nearly 40 times the rate in controls. When enalapril was administered to mice that had been depleted of plasma and renal renin by chronic sodium loading, plasma renin concentration increased markedly within 1.5 hours, but to only half the level achieved in the previously untreated mice. No decrease in renal renin occurred, suggesting that the renal renin remaining after chronic sodium loading was not available for release. Renal renin messenger RNA increased 4.5-fold after 6 hours, and after 8 days had increased to 5.0 times the level at day 0. The increase in calculated rate of renin synthesis was maximal between 5 and 8 days, when it was 54 times greater than at day 0. During enalapril treatment, there were marked increases in the granulation of the juxtaglomerular cells and in the amount of rough endoplasmic reticulum and Golgi apparatus they contained. These results suggest that posttranscriptional factors play a major role in determining the rate of renin synthesis.
Elevated nerve growth factor levels in young spontaneously hypertensive rats.
Authors: Donohue S J , Head R J , Stitzel R E
Published: June 2012

It is generally agreed that sympathetic innervation of vascular tissues in spontaneously hypertensive rats (SHR) is greater than that existing in vascular tissues from normotensive Wistar-Kyoto (WKY) rats. One factor responsible for regulation of the growth of peripheral sympathetic nerves is the peptide nerve growth factor, which is released from effector cells. In the present study, an enzyme immunoassay was used to measure nerve growth factor levels in mesenteric arteries (densely innervated) and aortas (sparsely innervated) from both young (20-day-old) and mature (6-month-old) SHR and WKY rats. The nerve growth factor content of mesenteric arteries and aortas from 20-day-old SHR was significantly greater than that present in corresponding tissues from WKY rats. In contrast, the nerve growth factor content found in mesenteric arteries and aortas of adult SHR did not differ significantly from that found in the corresponding adult WKY rat tissues. Moreover, when the tissues were obtained from adult animals, nerve growth factor levels were substantially higher in mesenteric arteries compared with aortas, regardless of the rat strain. These results support the hypothesis that the greater nerve growth factor content of vascular tissues from young SHR is involved in the early increased sympathetic innervation of blood vessels in this animal model of hypertension.
Molecular cloning of chromogranin A from rat pheochromocytoma cells.
Authors: Parmer R J , Koop A H , Handa M T , O'Connor D T
Published: June 2012

Chromogranin A (CgA) is the major soluble protein in catecholamine storage vesicles. To gain insight into its function, we isolated CgA clones from a size-selected lambda gt10 rat pheochromocytoma complementary DNA (cDNA) library. The longest cDNA insert identified was 2.2 kb and encoded the entire 462-amino acid open reading frame of rat CgA including an 18-amino acid hydrophobic signal peptide. Comparison of rat CgA with the recently published sequences of bovine CgA and human CgA revealed regions of strong homology at the N-and COOH-termini as well as variant areas predominantly in the middle portion of the molecule. Regions highly conserved and therefore suggestive of functional importance included 1) multiple paired basic residues, which may serve as proteolytic processing signals; 2) a region homologous to porcine pancreastatin, a putative modulator of peptide hormone release; and 3) a short hydrophobic disulfide loop region near the N-terminus that may have a role in the targeting of CgA to secretory vesicles. On the other hand, lack of conservation of the membrane attachment sequence arginine-glycine-aspartic acid argues against its functional importance in CgA. In addition, the presence of a unique polyglutamine region in rat CgA points to a possible messenger RNA (mRNA) splice junction. Northern blot experiments demonstrated the presence of an approximately 2.2 kb rat CgA mRNA in a neuroendocrine distribution (adrenal, brain, pheochromocytoma cells, but not skeletal muscle, heart, or kidney). Southern blot studies were consistent with the presence of a single CgA gene within the rat pheochromocytoma cell genome. Finally, comparison of the present rat pheochromocytoma cDNA clones with those recently obtained from normal rat adrenal gland reveals minor but apparently real differences that suggest CgA microheterogeneity.
Cardiovascular reactivity to the cold pressor test as a predictor of hypertension.
Authors: Menkes M S , Matthews K A , Krantz D S , Lundberg U , Mead L A , Qaqish B , Liang K Y , Thomas C B , Pearson T A
Published: June 2012

Cardiovascular reactivity to stress is hypothesized to be a marker for subsequent neurogenic cardiovascular disease, but few prospective studies of this hypothesis are available. We studied 910 white male medical students who had their blood pressure and pulse rate measured before and during a cold pressor test in the years 1948-1964. Hypertensive status (requiring drug treatment) was ascertained by annual questionnaires in the 20- to 36-year follow-up period. An association was observed between maximum change in systolic blood pressure and later hypertension, with a cumulative incidence of hypertension by age 44 of 6.7%, 3.0%, and 2.4% for a change in systolic blood pressure in the upper, middle two, and lowest quartiles, respectively (Kaplan-Meier, p less than 0.02). After adjustment for study entry age, Quetelet Index, cigarette smoking, pretest systolic blood pressure, and paternal or maternal history of hypertension in a Cox model, the association persisted. The excess risk associated with systolic blood pressure reactivity was not apparent until the population aged some 20 years and was most apparent among those in whom hypertension developed before age 45 (relative risk = 2.5, 95% confidence intervals = 1.47, 4.71 for a 20 mm Hg change). Diastolic blood pressure and heart rate changes were not associated with later hypertension. These data suggest that persons prone to later hypertension manifest an altered physiology at a young age.
Essential hypertension and histocompatibility antigens. A linkage study.
Authors: Gerbase-DeLima M , DeLima J J , Persoli L B , Silva H B , Marcondes M , Bellotti G
Published: June 2012

It is well established that genetic and environmental factors are involved in the etiology of essential hypertension. The presence of genes predisposing to essential hypertension in the human leukocyte antigen (HLA) complex is controversial because studies of an association between HLA antigens and essential hypertension have failed to yield consistent results. Our aim in the present study was to further investigate this issue through the method of linkage analysis. Analysis of 96 hypertensive siblings distributed in 31 families indicated a significant distortion (p = 0.0009) of the normal segregation pattern of inheritance of HLA haplotypes. Thus, our data indicate that at least one of the genes responsible for genetic predisposition to essential hypertension is located very near or within the HLA complex.
Hypothalamic GABA and sympathetic regulation in spontaneously hypertensive rats.
Authors: Wible J H , DiMicco J A , Luft F C
Published: June 2012

The posterior hypothalamus contains a sympathoexcitatory system that can be modulated by changes in GABAergic tone. We tested the hypothesis that the GABAergic mechanism in the posterior hypothalamus is altered in spontaneously hypertensive rats (SHR) compared with the Wistar-Kyoto (WKY) control rats. Blood pressure and heart rate were continuously measured in the conscious state; blood samples were obtained for determination of plasma catecholamine concentrations. Bilateral microinjections of the GABAA receptor antagonist bicuculline methiodide into the posterior hypothalamus increased heart rate and blood pressure in a dose-related fashion and increased plasma catecholamine concentrations in both SHR and WKY rats. The responses were not significantly different between the two strains of rats. Microinjections of the GABAA receptor agonist muscimol in this same region caused dose-related decreases in both heart rate and blood pressure in SHR and WKY rats. Although the decreases in heart rate caused by muscimol were not significantly different between the SHR and WKY rats, the decreases in blood pressure were significantly greater in SHR compared with WKY rats. Further, microinjection of muscimol caused a significant decrease in plasma catecholamines in SHR but not in WKY rats. These data indicate that in SHR and WKY rats the posterior hypothalamus contains a sympathoexcitatory mechanism that is tonically inhibited by GABA. The ability of muscimol to decrease plasma catecholamines selectively in SHR and to cause greater decreases in blood pressure, suggests that the GABAergic mechanisms in the posterior hypothalamus of the SHR and WKY rats may differ.
Long-term inhibition of angiotensin converting enzyme suppresses calcium channel agonist-induced contraction of aorta in hypertensive rats.
Authors: Sada T , Koike H , Miyamoto M
Published: June 2012

To elucidate functional changes in the vascular smooth muscle of spontaneously hypertensive rats (SHR) after chronic inhibition of angiotensin converting enzyme, we examined the contractile responses to different pharmacological interventions in the isolated aortas from SHR treated with a novel angiotensin converting enzyme inhibitor, CS-622 (10 mg/kg/day) for 20 weeks. In normal K+ medium, a marked contraction was elicited by increasing Ca2+ concentration from 0 to 3 mM in aortas from a control group of SHR, but not in aortas from SHR treated with CS-622. In 60 mM K+ medium, however, the sensitivity of aorta to Ca2+ was almost the same in the two groups. A calcium channel activator, CGP-28392 (10(-7) to 10(-6) M), induced a marked contraction in the aortas from control SHR, but not in the aortas from CS-622-treated SHR. When slightly depolarized in 10 or 12 mM K+ solution, the aortas from CS-622-treated SHR contracted in response to CGP-28392. The aortic sensitivity to KCl contraction was much lower in CS-622-treated SHR than in untreated SHR, whereas the sensitivity to phenylephrine contraction was little different in the two groups. These contractile profiles of aortas from CS-622-treated SHR were very similar to those from normotensive Wistar-Kyoto rats but not to those from hydralazine-treated SHR. These data suggest that contractions due to Ca2+ through voltage-dependent calcium channels are exaggerated in SHR aorta and that long-term treatment with angiotensin converting enzyme inhibitor suppresses the abnormal contractility of SHR vascular smooth muscle, probably through alterations of voltage-related functions of calcium channels.
Blood pressure in spontaneously hypertensive rats fed butterfat, corn oil, or fish oil.
Authors: Karanja N , Phanouvong T , McCarron D A
Published: June 2012

Dietary fats have been shown to influence blood pressure in humans and animal models of hypertension. The ability of a particular fat to modulate arterial pressure appears to depend on its fatty acid profile rather than its degree of saturation or unsaturation. Little is known about the effects of specific dietary fats of animal origin on blood pressure. We tested the concurrent effects of both calcium and dietary fat on blood pressure development in the spontaneously hypertensive rat. Sixty animals were fed diets containing butterfat, fish oil, or corn oil from 3-26 weeks of age. Each diet among the three oils was further modified to contain either 0.25% or 2.0% of the diet as calcium. All six diets provided 18% of the diet (36% of the calories) as fat. The polyunsaturated-to-saturated fat ratio was 0.07, 0.84, and 4.54 for butterfat, fish oil, and corn oil, respectively. Fish oil consumption resulted in lower blood pressures compared with butterfat (p less than 0.036) or corn oil (p less than 0.0009). Similarly, butterfat feeding resulted in lower blood pressures when compared with corn oil (p less than 0.054). Supplementing the diet with calcium decreased blood pressure in both the butterfat and corn oil diets. When butterfat diets were supplemented with calcium, the resulting blood pressures did not differ significantly from those obtained with the two fish oil diets. It is concluded that butterfat, though highly saturated, is associated with less of an increase in the spontaneously hypertensive rat's blood pressure than is corn oil, which is highly unsaturated.(ABSTRACT TRUNCATED AT 250 WORDS)
Extracellular calcium regulates expression of the gene for atrial natriuretic factor.
Authors: LaPointe M C , Deschepper C F , Wu J P , Gardner D G
Published: June 2012

Primary cultures of neonatal rat cardiocytes were exposed for 24 hours to culture media containing 0-2.0 mM extracellular calcium. Both atrial natriuretic factor (ANF) messenger RNA (mRNA) and ANF secretion were increased approximately threefold in the presence of 2.0 mM CaCl2 (vs. Ca2(+)-free medium). When cardiocytes were treated with the calcium channel blockers diltiazem, nifedipine, or verapamil, both ANF synthesis and secretion fell to 25-40% of control values. The choice of transcription start site on the ANF gene was not altered by the calcium channel blockers. When exogenous calcium was added to cardiocytes treated with verapamil, secretion of ANF was partially restored to control levels. High-performance liquid chromatographic analysis of medium from cardiocytes exposed to varying extracellular calcium concentrations or treated with calcium channel blockers for 24 hours revealed that the majority of secreted immunoreactivity (60-70%) migrated with pro-ANF (17 kDa) and that none of the various experimental manipulations significantly changed the ratio of pro-ANF to ANF in the media. These results were confirmed by immunoprecipitation analysis of the culture medium from the individual treatment groups. Treatment of cardiocytes for 24 hours with either the calcium ionophore A23187 or the phorbol ester 12-O-tetradecanoylphorbol 13-acetate increased ANF secretion. The combined use of these agents resulted in stimulation of both ANF secretion and ANF mRNA accumulation.
Influence of prostaglandins on papillary blood flow and pressure-natriuretic response.
Authors: Roman R J , Lianos E
Published: June 2012

The present study examined whether renal prostaglandins influence the pressure-natriuretic response by altering medullary hemodynamics or renal interstitial pressure. The diuretic and natriuretic responses to changes in renal perfusion pressure were compared in control rats (n = 15) and in rats receiving either meclofenamate (2 mg/kg, n = 9) or indomethacin (2 mg/kg, n = 4). In control rats, urine flow and sodium excretion increased from 10 +/- 2 to 118 +/- 10 microliters/min/g kidney wt and from 1.8 +/- 0.3 to 21.0 +/- 1.5 mueq/min/g kidney wt, respectively, when renal perfusion pressure was increased from 109 to 167 mm Hg. Urinary excretion of prostaglandin E2 and thromboxane B2 increased significantly by 152% and 190%, respectively. Meclofenamate lowered thromboxane B2 and prostaglandin E2 excretion and prevented the increase in eicosanoid excretion produced by elevations in perfusion pressure. The pressure-diuretic and pressure-natriuretic responses of rats given meclofenamate or indomethacin were approximately half of those observed in the control rats. Papillary blood flow increased 21% and renal interstitial pressure rose from 5.0 +/- 0.7 to 8.2 +/- 0.7 mm Hg in control rats when pressure was elevated from 100 to 150 mm Hg. Meclofenamate and indomethacin lowered papillary blood flow and renal interstitial pressure and blunted the increases in these values produced by elevations in perfusion pressure. These results support the view that renal prostaglandins modulate the pressure-natriuresis relation by altering renal medullary hemodynamics and suggest that an intact renal prostaglandin system is necessary for the full expression of the medullary hemodynamic and natriuretic responses to increases in renal perfusion pressure.
Reduced intracellular pH in lymphocytes from the spontaneously hypertensive rat.
Authors: Batlle D C , Saleh A , Rombola G
Published: June 2012

This study was designed to determine the cytoplasmic pH (pHi) profile of lymphocytes from a rat model of genetic hypertension that is well suited for study before and after the development of spontaneous hypertension. For this purpose, pHi was measured in thymic lymphocytes obtained from spontaneously hypertensive rats (SHR) and from age-matched Wistar-Kyoto (WKY) control rats using 2',7'-bis carboxyethyl-5,6-carboxyfluorescein (BCECF), a pH-sensitive fluorescence probe. At the age of 16-20 weeks, pHi of lymphocytes suspended in a HCO3-free HEPES-buffered solution, was markedly lower in the SHR than in the WKY rats (7.07 +/- 0.02, n = 16 and 7.22 +/- 0.01, n = 15, respectively, p less than 0.001), whereas systolic blood pressure was higher in SHR than in WKY rats (175 +/- 5.0 and 105 +/- 3.0 mm Hg, respectively, p less than 0.001). In rats less than 5 weeks of age, pHi was also lower in SHR than in WKY rat lymphocytes (7.12 +/- 0.04, n = 11 and 7.23 +/- 0.04, n = 11, respectively, p less than 0.05), although at this age systolic blood pressure was not different between the two groups (87 +/- 4.0 and 85 +/- 3.0 mm Hg, respectively). In lymphocytes suspended in a more physiological HCO3/CO2-buffered solution, pHi was again lower in the adult SHR than in the WKY rat (7.18 +/- 0.02, n = 16 and 7.31 +/- 0.02, n = 16, respectively, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
In vivo comparison of renal and femoral vascular sensitivity and local angiotensin generation.
Authors: Li T , Zimmerman B G
Published: June 2012

Experiments were conducted to compare the relative importance of the local renin-angiotensin systems in the rabbit renal and femoral vascular beds and their functional role in hemodynamic regulation. Angiotensin I (Ang I) (0.15 microgram/kg i.v.) elevated mean arterial blood pressure by 18 +/- 1 mm Hg in the renal experimental group and 19 +/- 1 mm Hg in the femoral experimental group; it decreased renal blood flow by 35 +/- 3% but increased femoral blood flow by 31 +/- 8%. All these effects were blocked by intravenous administration of captopril (2 mg/kg bolus injection plus 1 mg/kg/hr). Captopril also lowered mean arterial pressure by 17 +/- 3 and 16 +/- 2 mm Hg in the renal and femoral experimental groups, respectively, and it increased renal blood flow by 32 +/- 10% but reduced femoral blood flow by 21 +/- 4%. As a result, renal vascular resistance was decreased by 36 +/- 5%, but femoral vascular resistance remained unchanged. After captopril, plasma angiotensin II (Ang II) levels were decreased and Ang I levels increased in the two groups. The renal venous-arterial difference of Ang I was increased by captopril, but the femoral venous-arterial difference of Ang I was not, suggesting greater generation of Ang I in the kidney. In a separate group of bilateral nephrectomized rabbits, plasma Ang II levels as well as mean arterial pressure, femoral blood flow, and femoral vascular resistance were not changed by intravenous administration of captopril.(ABSTRACT TRUNCATED AT 250 WORDS)
Left ventricular structure and performance in middle-aged rats with deoxycorticosterone acetate-salt hypertension.
Authors: Tomanek R J , Barlow P A
Published: June 2012

We designed this study to establish the structural and functional characteristics of the hypertrophied left ventricle of middle-aged rats during mineralocorticoid-salt hypertension. Treatment was initiated at 12 months of age, and the rats were studied at either 13 or 15 months of age (after 1 or 3 months of treatment). All rats were unilaterally nephrectomized. One group received deoxycorticosterone acetate (DOCA) injections (30 mg/kg s.c.) biweekly and 1% NaCl drinking water (DOCA salt), and the other group was injected with the vehicle (sesame seed oil) and given tap water to drink (sham). During the first 4 weeks of DOCA-salt treatment, arterial pressure reached its peak and left ventricular enlargement was mainly due to increases of 47% in cardiocyte cross-sectional area in the middle layer of the left ventricular wall. The last 2 months were characterized by an accelerated endomyocardial growth. Because absolute left ventricular mass did not increase during the last 2 months of treatment, we conclude that cellular hypertrophy was accompanied by a focal loss of cardiocytes. Myocardial hydroxyproline concentration was initially elevated by 37% but normalized by the third month of treatment. Intracellularly, myofibril volume percent was not changed, but mitochondria volume percent declined (13% in the midmyocardium and 15% in the endomyocardium) and sarcoplasmic volume density increased by 25% and 39%, respectively, in these regions. Left ventricular hypertrophy was associated with enhanced peak cardiac and stroke indexes, measured during increased preload, after both 1 and 3 months of DOCA-salt treatment. Acceleration of flow, however, was depressed in the rats with left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Genetic, neurohumoral, and hemodynamic influences on spontaneously hypertensive rat heart development in oculo.
Authors: Tucker D C
Published: June 2012

To distinguish among genetic, neurohumoral, and hemodynamic explanations for structural and functional differences in the hearts of young spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) control rats, embryonic SHR and WKY rat heart tissue was cultured in the anterior eye chamber of adult SHR and WKY rats. In study 1, atria from E-12 WKY rat embryos grafted into anterior eye chambers of either SHR or WKY host rats achieved a larger size than did SHR grafts by 8 weeks in oculo (2.98 +/- 0.75 and 2.55 +/- 0.32 mm2 vs. 1.80 +/- 0.20 and 2.04 +/- 0.44 mm2). Beating rates did not differ between SHR and WKY rat atria implanted into SHR or WKY host rats. In study 2, ventricles from E-13 embryonic SHR and WKY rat hearts grew to similar size and weight when implanted into SHR or WKY host rats (e.g., SHR hearts, 1.81 +/- 0.32 vs. 1.74 +/- 0.33 mm2; WKY rat hearts, 1.75 +/- 0.29 vs. 2.29 +/- 0.32 mm2). Ventricle grafts from SHR embryos into SHR host rats beat more rapidly (165 +/- 19 beats/min) during weekly measurements than either WKY rat ventricles (92 +/- 9 beats/min in SHR hosts and 99 +/- 9 beats/min in WKY host rats) or SHR ventricles grafted into WKY host rats (109 +/- 7 beats/min, p less than 0.001). In study 3, atria from E-13 SHR and WKY rat embryos were grafted into sympathectomized and intact eye chambers of SHR or WKY host rats. Sympathectomy of the eye chamber compromised growth of grafts into WKY host rats (1.54 +/- 0.24 vs. 0.90 +/- 0.14 mm2) but not SHR hosts (1.54 +/- 0.25 vs. 1.73 +/- 0.24 mm2). Grafts into sympathectomized eye chambers of WKY host rats beat more slowly than grafts into eye chambers with sympathetic innervation intact (282 +/- 14 vs. 202 +/- 14 beats/min); sympathectomy did not alter beating rate of grafts in SHR hosts (266 +/- 14 vs. 255 +/- 18 beats/min). These results suggest that the growth and beating rate of SHR atrial grafts may be less sensitive to sympathetic innervation than WKY rat atrial grafts. In these studies, SHR grafts did not grow larger than WKY heart grafts and did not show an increased intrinsic beating rate, suggesting that the cardiac hypertrophy and increased intrinsic beating rate observed in intact SHR are unlikely to result from direct genetic programming.
Modulation of episodic renin release during sleep in humans.
Authors: Brandenberger G , Krauth M O , Ehrhart J , Libert J P , Simon C , Follenius M
Published: June 2012

We previously described a strong concordance between nocturnal oscillations in plasma renin activity and sleep cycles. To examine whether modifying renal renin content or release influences the response to central stimuli linked to sleep stage alternation, plasma renin activity was measured every 10 minutes from 11:00 PM to 8:00 AM in three groups of six subjects. The first group received one 40 mg dose of the diuretic furosemide; the second group underwent the night experiment after 3 days on a low sodium diet; the third group received one 100 mg dose of the beta-blocker atenolol. Each subject underwent a control night when a placebo was given. The nocturnal curves were analyzed with a pulse detection program. For the control nights, 74 of the 83 sleep cycles were associated with significant plasma renin activity oscillations; non-rapid eye movement sleep occurred in the ascending portions and rapid eye movement sleep in the declining portions of the oscillations. These oscillations persisted in the three groups of subjects during the experimental nights and the relation with the sleep stages was not disturbed. Acute stimulation by furosemide amplified the oscillations and led to a general upward trend of the nocturnal profiles. Similarly, a low sodium diet, which led to a slow increase in renal renin content, provoked large oscillations with high initial levels. However, in both cases the mean relative amplitude of the oscillations, expressed as a percentage of the nocturnal means, was similar to that of the control nights and approximated 60%.(ABSTRACT TRUNCATED AT 250 WORDS)
Time course of enhanced adrenal responsiveness to angiotensin on a low salt diet.
Authors: Rogacz S , Williams G H , Hollenberg N K
Published: June 2012

To assess the rate of activation of the renin-angiotensin-aldosterone axis and enhancement of adrenal responsiveness to angiotensin II (Ang II) with restriction of sodium intake, 16 healthy male subjects were placed initially on a 200 meq daily sodium intake; adrenal responsiveness to Ang II was assessed, and then daily sodium intake was reduced abruptly to 10 meq. Adrenal responses to Ang II were assessed again during the non-steady state interval 24 and 48 hours later, and after balance was achieved in 5-7 days. Renin-angiotensin system activation was evident within 24 hours after sodium intake was restricted. The increase in basal plasma aldosterone concentration and enhancement of the adrenal response to Ang II, on the other hand, tended to lag. Within 24 hours of restricting sodium intake, despite a significant increase in both plasma renin activity (1.0 +/- 0.2 vs. 2.4 +/- 0.7 ng/ml/hr, p less than 0.01) and Ang II concentration (22.0 +/- 1.9 vs. 29.5 +/- 1.3 pg/ml, p less than 0.05), there was no increase in basal plasma aldosterone concentration (10.4 +/- 1.3 vs. 11.7 +/- 1.2 ng/dl). At 48 hours, despite little further change in plasma renin activity or plasma Ang II concentration, there was a sharp increase in basal plasma aldosterone concentration (22.5 +/- 3.6 ng/dl, p less than 0.01). The adrenal response to Ang II was increased significantly at 24 hours, evident at only a 10 ng/kg/min dose, but showed progressive further enhancement with time.(ABSTRACT TRUNCATED AT 250 WORDS)
Subclasses of cyclic GMP-specific phosphodiesterase and their role in regulating the effects of atrial natriuretic factor.
Authors: Weishaar R E , Kobylarz-Singer D C , Keiser J , Haleen S J , Major T C , Rapundalo S , Peterson J T , Panek R
Published: June 2012

Two subclasses of cyclic guanosine monophosphate (GMP)-specific phosphodiesterases were identified in vascular tissue from several beds. The activity of one subclass (phosphodiesterase IB) was stimulated severalfold by calmodulin and selectively inhibited by the phosphodiesterase inhibitor TCV-3B. The activity of the other subclass (phosphodiesterase IC) was not stimulated by calmodulin and was selectively inhibited by the phosphodiesterase inhibitor M&B 22,948. To assess the involvement of both subclasses in regulating cyclic GMP-dependent responses, the ability of TCV-3B and M&B 22,948 to potentiate the in vitro and in vivo responses to the endogenous guanylate cyclase stimulator atrial natriuretic factor (ANF) was evaluated. Both TCV-3B and M&B 22,948 relaxed isolated rabbit aortic and pulmonary artery rings and also potentiated the relaxant effect of ANF. In addition, both inhibitors produced small increases in urine flow and sodium excretion in anesthetized rats and potentiated the diuretic and natriuretic responses to exogenous ANF. M&B 22,948 (30 micrograms/kg/min) produced a threefold increase in the natriuretic response to simultaneously administered ANF, and TCV-3B (10 micrograms/kg/min) produced a twofold increase in the response to ANF. The results of the present experiments suggest that both the calmodulin-sensitive and calmodulin-insensitive subclasses of cyclic GMP-specific phosphodiesterase play a role in regulating the in vitro and in vivo response to ANF.
Vascular capacitance in rats subjected to chemical renal medullectomy.
Authors: Edmunds M E , Russell G I , Burton P R , Swales J D
Published: June 2012

Selective renal medullary destruction is produced in rats by a single injection of 2-bromoethylamine hydrobromide. The object of these studies was to investigate whether destruction of the renal medulla in normal rats would alter vascular capacitance. Conscious bromoethylamine-treated rats (n = 15) were compared with control saline-injected rats (n = 12). Mean circulatory filling pressure was measured during a brief circulatory arrest caused by inflation of a right atrial balloon. Blood volume was determined from plasma volume (iodine-125-labeled albumin) and hematocrit. Mean circulatory filling pressure was measured at resting blood volume and after rapid blood volume changes. Vascular compliance was derived from the mean circulatory filling pressure-blood volume curve. The bromoethylamine-treated rats were significantly hypertensive compared with control rats (mean arterial pressure 133 +/- 2 and 114 +/- 3 mm Hg, respectively, p less than 0.001) and had a significant tachycardia (475 +/- 8 and 443 +/- 10 beats/min, respectively, p = 0.02). Blood volume, plasma volume, hematocrit, and sodium excretion were no different. There was no significant difference in mean circulatory filling pressure (6.5 +/- 0.2 and 6.8 +/- 0.2 mm Hg, respectively, p = 0.4) or vascular compliance (3.64 +/- 0.20 and 3.53 +/- 0.12 ml/kg/mm Hg, respectively, p = 0.7). The position of the vascular pressure-volume curve was unchanged indicating no change in vascular capacity. This would suggest that the destruction of renal medullary vasodepressor mechanisms does not result in alterations in vascular capacitance.
Effects of ouabain and low sodium on contractility of human resistance arteries.
Authors: Woolfson R G , Hilton P J , Poston L
Published: June 2012

Earlier work with rat arteries has resulted in a widely held assumption that resistance artery smooth muscle will not contract on exposure to a reduced transplasmalemmal sodium gradient. In view of the well-recognized low sensitivity of rat tissue to cardiac glycosides, we have investigated the effects of altering the transplasmalemmal sodium gradient on vascular smooth muscle tone by using human resistance arteries. Incubation of arteries in low sodium or in ouabain to inhibit active sodium efflux for 1 hour increased the contractile response to caffeine stimulation; this finding indicated enhanced calcium buffering by the sarcoplasmic reticulum. Prolonged incubation in ouabain in the presence of phentolamine or diltiazem resulted in a concentration-dependent increase in the tone of resting human resistance arteries. Reduction of the transplasmalemmal sodium gradient by incubation in low sodium buffer effected an increase in tone similar to that obtained in the presence of ouabain. These results suggest that alteration of the transplasmalemmal sodium gradient may increase the vascular smooth muscle tone of human resistance arteries by altering intracellular calcium handling. This is a new finding in human resistance arteries and may involve inhibition and, indeed, reversal of sodium-dependent calcium efflux. A concentration-dependent potentiation of tone was found after the addition of ouabain to submaximally activated arteries. Sodium-calcium exchange may also play a pivotal role in this mechanism.
Chronic hypertension produced by infusion of endothelin in rats.
Authors: Mortensen L H , Pawloski C M , Kanagy N L , Fink G D
Published: June 2012

Endothelin, a potent vasoconstrictor peptide synthesized by the vascular smooth muscle endothelium, was chronically infused into male Sprague-Dawley rats to determine whether a long-term increase in circulating endothelin levels would cause a sustained elevation in mean arterial pressure. Rats were catheterized, housed in metabolic cages, and maintained on a fixed 6 meq/day sodium intake throughout the experiment with daily measurements including mean arterial pressure, heart rate, water intake, urine output, urinary sodium excretion, urinary potassium excretion, cardiac output, total peripheral resistance, and stroke volume. Infusion of endothelin-1 (ET-1) at rates of 3, 5, or 7.5 pmol/kg/min for 7 days was associated with significant, sustained, and dose-dependent increases in mean arterial pressure and smaller less consistent elevations in total peripheral resistance. Other parameters were unaffected. Similar results were observed in rats receiving endothelin-3 (ET-3), except that a higher dose of ET-3 was required. These results indicate that elevated blood levels of endothelin could produce a maintained hypertension without sodium or water retention and that the hemodynamic basis for the increased mean arterial pressure is similar to that seen in most other forms of experimental and clinical hypertension.
Renal effects of Fab fragments of kinin antibodies on deoxycorticosterone acetate-salt-treated rats.
Authors: Tomiyama H , Scicli A G , Scicli G M , Carretero O A
Published: June 2012

The role of the renal kallikrein-kinin system in the regulation of renal function is not completely understood. Intrarenal kinins can influence renal function by acting as paracrine hormones at basolateral, luminal, or both sites in the distal nephron. To examine the role of intrarenal kinins in deoxycorticosterone acetate-salt-treated rats, which have high renal kallikrein, Fab fragments of antibradykinin antibody or DArg[Hyp3Thi5,8DPhe7]bradykinin, a kinin antagonist, were used to block kinins. At the dose used, the antibody (25 mg) and kinin antagonist (10 micrograms/min/rat) inhibited the hypotensive effect of intra-arterially injected bradykinin (100 ng) by 70% and 52%, respectively. The antibody appeared in the urine within 30 minutes after administration. Urinary volume was lowered from 9.4 +/- 0.2 to 6.7 +/- 0.4 microliters/min/g kidney wt (p less than 0.001, paired t test) by the antibody and from 8.5 +/- 0.3 to 6.8 +/- 0.4 microliters/min/g kidney wt (p less than 0.004, paired t test) by the kinin antagonist. The antibody lowered urine sodium excretion from 1.11 +/- 0.04 to 0.88 +/- 0.06 mueq/min/g kidney wt (p less than 0.001, paired t test), whereas the kinin antagonist had no significant effect. Neither altered blood pressure, renal blood flow, or glomerular filtration rate. These data suggest that in deoxycorticosterone acetate-salt-treated rats, excretion of water and sodium is regulated in part by kinins. The antidiuretic effect of the antibody and kinin antagonist might be due to blockade of kinins in the vascular-interstitial space of the kidney, since the kinin antagonist is likely hydrolyzed in the proximal tubule and does not reach the lumen of the distal nephron.(ABSTRACT TRUNCATED AT 250 WORDS)