Impact of salt intake on blood pressure and proteinuria in diabetes: importance of the renin-angiotensin system

Patients with hypertension and diabetes are frequently salt-sensitive. Consequently, increasing dietary salt intake results in a rise in systemic arterial pressure and an increase in proteinuria, as well as a progressive risk for developing renal injury. A difference in the renal hemodynamic response to salt appears, at least in part, to determine how the salt intake affects blood pressure. Greater dietary salt intake in salt-sensitive patients results in a blunted rise in renal plasma flow and an increase in body weight. Greater dietary salt consumption also results in a rise in glomerular filtration fraction and increasing proteinuria. Pharmacologic antagonism of the renin-angiotensin system helps restore the blunted renal plasma flow response to high salt intake and correlates with the fall in mean arterial pressure. Consequently, the pressor response to increasing dietary salt consumption in patients with diabetes and hypertension may be related to insufficient renal vasodilation, perhaps due to inadequate suppression of the renin-angiotensin system. Moreover, inadequate suppression of the renin-angiotensin system within the kidney results in an increase in efferent glomerular arteriolar tone and a rise in glomerular capillary pressure, increased proteinuria and a greater risk for renal injury. Many of the coexisting cardiovascular risk factors associated with salt sensitivity may be explainable in part by the overactivity of the renin-angiotensin system.     

Salt sensitive blood pressure and the renin-angiotensin system in hypertension

The relationship between (excessive) use of sodium chloride and the blood pressure is still equivocal. Blood pressure responses to alterations in dietary salt consumption vary greatly between individuals, which has led to the concept of salt sensitivity. Although the mechanisms which determine the degree of salt sensitivity are not fully understood, the renin-angiotensin system seems to play a key role. A relative inability of this system to respond promptly to alterations in salt intake may underlie the development of salt sensitivity. By administering drugs which block the renin-angiotensin system to patients with essential hypertension, blood pressure is rendered more sensitive to the effects of salt restriction and (or) diuretic treatment.     

Effect of 1,25 (OH)2 vitamin D3 on glomerulosclerosis in subtotally nephrectomized rats

In the past, there has been considerable concern that treatment with active vitamin D might accelerate progression independent of hypercalcemia and hypercalcuria. Nevertheless, 1,25(OH)2D3 has known antiproliferative properties and has also been shown to inhibit renal growth. Since glomerular growth is a permissive factor for the development of glomerulosclerosis, we reasoned that 1,25(OH)2D3 might even attenuate progression. To test this working hypothesis we performed two experiments of 8 and 16 weeks duration, respectively, to compare subtotally nephrectomized (SNX) rats treated with ethanol and SNX treated with 1,25(OH)2D3. Control animals were sham operated and pair-fed with SNX animals. 1,25(OH)2D3 (3 ng/100 g body wt/day) was administered by osmotic minipump. 1,25(OH)2D3 had no significant effect on systolic blood pressure and only a transient effect on weight gain. SNX reduced the number of glomeruli (left kidney) from an average of 3.3 x 10(4) to 1.2 x 10(4) per kidney. Mean glomerular volume was 3.87 +/- 0.71 x 10(6) microns 3 in sham operated animals and significantly (P < 0.05) higher (10.1 +/- 1.75 x 10(6) microns 3) in untreated animals 16 weeks after SNX. Glomerular volume was significantly (P < 0.05) less in 1,25(OH)2D3 treated SNX [10.1 +/- 1.75 in ethanol vs. 7.04 +/- 1.78 in 1,25(OH)2D3 treated SNX]. In parallel, there was significantly (P < 0.01) less glomerulosclerosis [glomerulosclerosis index 1.16 +/- 0.14 in the ethanol treated SNX vs. 0.80 +/- 0.16 in SNX treated with 1,25(OH)2D3] in the eight week experiment. Albuminuria was significantly (P < 0.01) lower in 1,25(OH)2D3 treated than in ethanol treated SNX (mean 0.785 mg/24 hr, range 0.43 to 1.80, vs. 3.75 mg/24 hr, 1.29 to 14.2). The morphological data were directionally analogous in a second 16 week experiment. Only slight changes of the vascular sclerosis index and tubulointerstitial index were seen in SNX and were not affected by 1,25(OH)2D3 further. To prove that the effect of 1,25(OH)2D3 was independent of PTH, parathyreoidectomized SNX rats without or with 1,25(OH)2D3 treatment were examined seven days post-SNX. PCNA staining showed suppression of cell proliferation. Furthermore, in situ hybridization for transforming growth factor-B (TGF-beta) showed less vascular and tubular expression in 1,25(OH)2D3 treated rats. We conclude that 1,25(OH)2D3 has antiproliferative actions during the compensatory growth of nephrons in response to subtotal nephrectomy. These effects are independent of PTH. The data document that 1,25(OH)2D3 reduces renal cell proliferation and glomerular growth as well as glomerulosclerosis and albuminuria as indicators of progressive glomerular damage.     

The effect of dietary sodium intake on the blood pressure and cardiac output responses to angiotensin II in unanaesthetized rats

1. Dose-response curves for the pressor activity of angiotensin II have been determined in unanaesthetized rats receiving diets containing 2-5% (w/w) or 0-007% (w/w) sodium and administered in various sequences. 2. Dose-response curves were shifted to the left in rats on a high-, compared with a low-, sodium intake. This response was maintained for 7 days on changing from high to low sodium. 3. There was no difference in the relation between the fall of cardiac output and the rise of blood pressure in any of the experimental groups. 4. Dose-response curves for peripheral resistance showed the same directional change as seen for the pressor response in rats on high- and low-sodium diets. Since depression of cardiac output was proportional to the pressure rise, the absolute change in peripheral resistance was greater than the blood pressure response. The proportional changes were similar. 5. It is concluded that alterations in the pressor response to angiotensin caused by changes in sodium loading are attributable to changes in peripheral resistance and not to changes in the cardiac output response to the acute rise in blood pressure.     

Role of the brain renin-angiotensin system in the maintenance of blood pressure in conscious spontaneously hypertensive and sinoaortic baroreceptor-denervated rats

1. Evidence suggesting an involvement of the brain renin-angiotensin system (RAS) in the development/maintenance of hypertension in spontaneously hypertensive rats (SHR) relies, in part, on early experimental data reporting centrally mediated antihypertensive effects of saralasin. However, recent data using non-peptide AT1 receptor antagonists does not always support this theory because these compounds usually do not lower blood pressure when given centrally. 2. In the present study we have re-assessed the central effects of saralasin in conscious SHR as well as in sinoaortic baroreceptor-denervated (SAD) rats. Both of these models exhibit heightened sensitivity to the central pressor effects of angiotensin II (AngII) and, thus, any potential antihypertensive activity would provide functional evidence of activated brain RAS mechanisms in these models. 3. In SHR, saralasin failed to lower mean arterial pressure (MAP) when given intracerebroventricularly (i.c.v.) as bolus or infusion doses that blocked the centrally mediated pressor effect of AngII. 4. In SAD rats, there was a marked impairment of the baroreceptor-heart rate reflex function and enhanced centrally mediated pressor responses to AngII. However, i.c.v. saralasin infusions again did not alter MAP. 5. Collectively, these results suggest that the central RAS is not involved in the maintenance of MAP in SHR and SAD rats, both of which are models exhibiting a functional hyperresponsiveness to AngII.     

A comparative study of blood pressure and sodium intake in Belgium and in Korea

A comparative blood pressure and sodium excretion were higher in Korea than in Belgium. By multiple regression and covariance analysis an independent positive association between sodium and blood pressure and a negative correlation between potassium and blood pressure were found in some population subgroups and in the total population studied in Korea. In Belgium a positive association between sodium and blood pressure was found when higher powers of age, height, weight and sodium were included in the analysis. The independent influence of sodium on blood pressure was relatively small, amounting to about 2 mm Hg of pressure rise for an increase in 24-h excretion of 100 mmol of sodium.     

Effects of drug-induced changes in resting blood pressure on classically conditioned heart rate and blood pressure in restrained rats.

Subsequent to receiving aversive classical conditioning (which led to a decelerative heart rate [HR] CR and a pressor–depressor blood pressure [BP] CR), 3 groups of restrained male Sprague-Dawley rats received iv infusion of Na nitroprusside (n?=?9; 40 μg/mg/min) to lower baseline BP, phenylephrine (n?=?10; 17 μg/mg/min) to raise baseline BP, or an equivalent volume of saline (n?=?9). Conditioning test trials during infusion revealed that hypotension produced by Na nitroprusside eliminated the HR CR and transformed the BP CR into a pressor-only reaction. Hypertension produced by phenylephrine facilitated the HR CR and changed the BP CR to a pressor-only response on trials in which baseline BP increases and baseline HR decreases were within restricted limits. Following drug withdrawal, the HR CRs of both drug groups and the BP CR of the phenylephrine group were attenuated. The UCRs to the shock UCS under phenylephrine were exaggerated and consisted of tachycardias and depressor BP changes, whereas, under Na nitroprusside, reduced tachycardias and depressor activity occurred. Results suggest that the loss of the vagally medicated HR CR under Na nitroprusside was due to baroreceptor-controlled inhibition of vagal discharge. The enhancement of the HR CR under phenylephrine was due to baroreceptor-influenced facilitation of vagal discharge. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ascites fluid of nephrotic rats: sodium dodecyl sulphate-polyacrylamide gel electrophoresis protein pattern and the renin-angiotensin system

1. The concentration of renin and angiotensinogen (Ao) and the activity of angiotensin I-converting enzyme (ACE) was measured in the ascites fluid of nephrotic rats obtained 8 days after puromycin aminonucleoside (PAN) injection. 2. Ascites fluid, serum and urine proteins of these rats were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). 3. Renin, Ao and ACE were found in the ascites fluid and the percentage of the ratio ascites fluid/(plasma or serum) ranged from 5.9 to 9.9%. The electrophoretic analysis revealed that the ascites fluid contained low (Mr < 66 kDa) and high (Mr < 66 kDa) molecular weight proteins. Albumin and six proteins higher than 66 kDa were present both in the ascites fluid and in serum from nephrotic rats. 4. Data from the study suggest that some proteins in the ascites fluid, including renin, Ao and ACE, come from the plasma. It is possible that the loss of renin, Ao and ACE to the ascites fluid may be playing a role in the metabolic alterations of these three proteins in PAN-nephrotic rats.     

Effects of moxonidine and clonidine on renal function and blood pressure in anesthetized rats

OBJECTIVES: This study was conducted 1) to characterize through SEM analysis the resin-dentin interface produced by single-bottle primer/adhesives and a three-component system [Scotchbond Multi-Purpose (3M Dental)] and 2) to evaluate the shear bond strength to dentin of these adhesive systems. METHODS: Single-bottle primer/adhesives [Bond 1 (Jeneric/Pentron), Single Bond, (3M Dental Products); One Step (Bisco Inc.), OptiBond Solo (Kerr Corp.), Prime & Bond 2.1 (L.D. Caulk-Dentsply), Syntac Single-Component (Ivoclar-Vivadent), Tenure Quilk with Fluoride (Den-Mat)] were used according to manufacturers' instructions to bond resin composite to flat dentinal surfaces of extracted human third molars (n = 15). All samples were thermocycled 300x. Twelve specimens per group were used to measure shear bond strength and three specimens were used to evaluate the interfacial morphology under SEM. A one-way ANOVA and Turkey's test were used to assess the results. RESULTS: Mean shear bond strengths in MPa +/- SD for the groups ranged from 22.27 +/- 4.5 MPa for Single Bond to 7.6 +/- 3.9 MPa for Syntac Single-Component. The statistical analysis indicated that Single Bond produced significantly higher (p < 0.001) bond strengths than Syntac Single-Component, Prime & Bond 2.1, Bond 1 and Tenure Quik With Fluoride. Bond strengths for Syntac Single-Component were significantly lower than One-Step, OptiBond Solo, Scotchbond Multi-Purpose Plus and Single Bond. SEM examination clearly revealed the formation of a distinct hybrid layer for all adhesive systems; however, minor variations in ultrastructure existed among products. SIGNIFICANCE: Some single-bottle primer/adhesive present in vitro bond strengths and hybrid layer formation similar to those found for the conventional three-component adhesive system tested.     

Effects of clonidine and flesinoxan on blood pressure variability in conscious spontaneously hypertensive rats

Several species of scolopenders (Chilopoda: Scolopendridae), with their bites, are often cause of a local burning pain, redness, edema and sometimes leading to an erysipelas-like state. The present note deals with the main morphological characteristics useful for identificating of Scolopendra cingulata, the most common Italian species of Scolopendridae. Moreover, biology, ecology and medical aspects of the bite are discussed and two human cases due to S. cingulata bite occurred in Latium region (Italy) are described.     

Involvement of renin-angiotensin system in hypertensive effect of cadmium in rats

Role of renin-angiotensin system in hypertension induced by cadmium chloride (CdCl2) in rats has been investigated. Intravenous administration of CdCl (1 mg/kg) produced a biphasic response i.e. a transient fall followed by a marked and consistent rise in blood pressure. The peak hypertensive effect was accompanied by raised PRA levels. Pretreatment with captopril (1 mg/kg, i.v.) losartan (1 mg/kg, i.v.) or captopril + losartan attenuated the pressor response to Cd by 62%, 42% and 100% respectively in separate groups. Central administration of Cd (10 micrograms/rat, i.c.v.) showed a biphasic response similar to that observed after i.v. route. However, it was not accompanied by raised PRA levels. Prior treatment with losartan (10 micrograms/rat, i.c.v.) completely abolished the pressor response to Cd (i.c.v.) whereas it was not affected significantly by captopril (10 micrograms/rat, i.c.v.). On the other hand, centrally administered losartan only partially reduced the pressor response to i.v. Cd. The results are discussed in light of a differential involvement of central vs peripheral renin-angiotensin system in the hypertensive effect of Cd.     

Effect of chronic captopril treatment on circulating and tissue renin-angiotensin system in SHR rats

This study investigated spectral differences in the phonation of vowels between a group of 21 children with velopharyngeal impairment and a paired control group of 42 subjects. The speech material was composed of the isolated vowels /a/, /i/, and /u/, a sustained vowel /a/, and four vowels included in spoken words: two nasals /in/ and /on/ in dindon, and two orals /a/ and /o/ in gateau. A bottom-up discriminant function analysis indicated that the cepstrum coefficients and the linear-FFT were the most efficient tools in the test to classify the set of children. They were superior to the results obtained with the formant-representation of the vowels. The use of a perceptive scale (barks) did not improve the results. Discrimination over the total group showed percentages lower than those obtained when boys and girls were assessed separately. The best discriminating results were obtained with the /a/ of gateau for the girls and with the isolated /i/ for the boys.     

Effects of intraventricular and intraspinal 6-hydroxydopamine on blood pressure of renal hypertensive rats

6-Hydroxydopamine (6-OH-DA) was administered into the lateral brain ventricle of normal rats and of rats with renal hypertension produced by unilateral clipping of the renal artery, and was also administered into the spinal cord of normal rats. Intraventricular administration of 6-OH-DA prevented the development of renal hypertension in rats, but was ineffective in developed renal hypertension. The development of renal hypertension was not affected by pretreatment with intraspinal injection of 6-OH-DA, which produced a marked reduction only in spinal cord noradrenaline. These data suggest that brain adrenergic neurones may participate in the production of renal hypertension but the noradrenergic projections in the spinal cords are not essential for this process.     

Effects of dantrolene sodium on progression of left ventricular hypertrophy induced by pressure overload in rats

We studied the long-term effects of dantrolene sodium (D), a specific sarcoplasmic reticulum (SR) Ca2+-release inhibitor, on the progression of left ventricular pressure-overloaded hypertrophy in rats. We treated abdominal aorta-constricted rats with one of two doses of D for 4 weeks. The extent of hypertrophy was expressed as the ratio of left ventricle to body weight. Hemodynamic parameters were measured by using a microtip catheter manometer. Although a low dose of D (500 mg/L in drinking water) decreased blood pressure to normal levels, the progression of cardiac hypertrophy was not inhibited. In contrast, a high dose of D (5 mg/kg, i.p.) also reduced blood pressure and inhibited the progression of cardiac hypertrophy. Dantrolene sodium had no effect on cardiac function in sham-operated rats. Thus control of Ca2+ release from the SR might be crucial in regulating the progression of cardiac hypertrophy, the final mediator possibly being intracellular Ca2+ concentration.     

Effects of lisinopril on stress-induced peak blood pressure and sodium excretion: a double-blind controlled study

Hirudin is an anticoagulant originally extracted from the leech Hirudo medicinalis. Using recombinant DNA technology a new compound, recombinant desulphato hirudin CGP 39393 has now been produced. The aim of this study was to determine the maximum tolerated dose in patients undergoing elective hip replacement. This open safety trial represents, to our knowledge, the first experience of recombinant hirudin in orthopedic patients. In this study 48 patients undergoing primary total hip replacement were included and the safety of subcutaneous injections of 10, 15, 20 and 40 mg CGP 39393 twice daily, was evaluated. Prophylaxis was started immediately pre-operatively and continued for 8-10 days. A mandatory bilateral phlebography was performed at the end of the prophylactic treatment period and a clinical follow-up was done 6 weeks after surgery. A major bleeding event occurred in the first 3 patients receiving 40 mg CGP 39393 b.i.d. and the prophylaxis regimen at this dosage level was therefore discontinued. Median values of total blood loss and requirements of blood transfusion in the patients receiving 10-20 mg CGP 39393 were similar to those reported in previous studies on total hip replacement performed at the same centre, using other prophylactic drugs. Deep vein thrombosis (DVT) was confirmed by phlebography in 5 out of 12 patients in the 10 mg group (41.7%, 95% confidence limits [CL]: 15.2-72.3%), 1 out of 11 patients in the 15 mg group (9.1%, CL: 0.23-41.3%) and 2 out of 20 patients in the 20 mg group (10.0%, CL: 1.2-31.7%) during the prophylaxis period. CGP 39393 was safe and well tolerated, when administered as subcutaneous injections of 10-20 mg twice daily. The dose level of 40 mg CGP 39393 twice daily resulted in serious disturbance of the hemostasis in patients after hip prosthesis surgery.     

Effects of extract from Clerodendron trichotomum on blood pressure and renal function in rats and dogs

A number of factors may determine the diagnostic accuracy of digitized intraoral radiographs. Conventional film radiographs were digitized with three different digitizers, a laser-scanner, a drum-scanner and a TV camera. Digital images, varying in pixel size, grey level and image processing, were displayed on three different video-monitors and assessed by 10 dentists. The detectability of incipient proximal surface caries was used as an index of the diagnostic accuracy and the effect of the different factors compared by means of receiver operating characteristic (ROC) analysis. Images digitized by the drum-scanner were found to have the best diagnostic accuracy. Sufficient diagnostic accuracy could be attained on the low-cost video monitor of a personal computer. Digital images with a pixel size of 100 microns and 32 grey levels were found to be acceptable for intraoral radiographs for diagnostic purposes. These results provide a practical guide for establishing a digital image acquiring system for any intraoral radiographs, reducing demands on data storage to a minimum.