Age-associated changes in intestinal fructose uptake are not explained by alterations in the abundance of GLUT5 or GLUT2

A reduction in nutrient absorption may contribute to malnourishment in the elderly. The objectives of this study were to determine the effects of aging on the absorption of fructose in rats, as well as the mechanisms of these adaptive changes. Male Fischer 344 rats aged 1, 9, and 24 months were fed standard Purina chow for 2 weeks (PMI #5001, PMI Nutritionals, Brentwood, MO). The uptake of (14)C-labeled D-fructose was determined in vitro using the intestinal sheet method. Intestinal samples were taken for RNA isolation and for brush border membrane (BBM) and basolateral membrane (BLM) preparation. Northern blotting, Western blotting, and immunohistochemistry were used to determine the effects of age and diet on GLUT5 and GLUT2. When expressed on the basis of intestinal or mucosal weights, aging was associated with a decline in jejunal and ileal fructose uptake, whereas jejunal fructose uptake was increased when expressed on the basis of serosal or mucosal surface area. The alterations in fructose uptake were not paralleled by changes in GLUT5 or GLUT2 abundance. These results indicate that 1) the effect of age on fructose uptake depends on the method used to express results, and 2) the age-associated changes in uptake are not explained by alterations in GLUT5 and GLUT2.     

Intestinal brush border calcium uptake in spontaneously hypertensive rats and their genetically matched WKY rats

The current studies were designed to characterize calcium transport by intestinal brush border membrane in the spontaneously hypertensive rat (SHR) and normotensive control, the Wistar-Kyoto (WKY) rat. The biochemical and functional purity of the intestinal brush border membranes in SHR and WKY rats was validated by marker enzymes and the ability to transiently transport D-glucose in the presence of Na+ gradient. Calcium transport into duodenal and jejunal vesicles represented a minor binding component and transmembrane movement as evident by initial rate studies, A23187 studies, and lanthanum displacement experiments. Initial rate and time course of calcium uptake was lower in SHR compared with WKY rats. Kinetic analysis of calcium uptake by the jejunum (total uptake minus binding component) showed a Vmax of 6.98 +/- 0.2 and 1.8 +/- 0.2 nmol/mg protein/7 sec in WKY rats and SHR, respectively (P less than 0.001), whereas Km values were 0.76 +/- 0.04 and 0.87 +/- 0.1 mM for WKY rats and SHR, respectively. Similar kinetic analysis of calcium uptake by the duodenal segments showed a Vmax of 10.3 +/- 0.8 and 2.8 +/- 0.2 nmol/mg protein/7 sec in WKY rats and SHR, respectively (P less than 0.01). Km values were 0.7 +/- 0.2 and 0.3 +/- 0.06 mM (P greater than 0.05). Vmax of calcium uptake in the 2-week-old rats (prehypertensive period) was 6.0 +/- 0.3 and 3.53 +/- 0.3 nmol/mg protein/7 sec in WKY rats and SHR, respectively (P less than 0.001), whereas Km values were 0.60 +/- 0.07 and 0.5 +/- 0.01 mM, respectively. These results suggest that calcium binding and uptake by duodenal and jejunal intestinal brush border membranes of SHR is significantly decreased compared with WKY rats. The decrease in transmembrane calcium uptake is secondary to decrease in Vmax and is present before the appearance of hypertension, implying a genetically determined defect in calcium uptake in intestinal brush border membranes of the SHR.     

Calcium uptake kinetics into brush-border membrane vesicles: higher Vmax in the spontaneously hypertensive rat than in normotensive control

Arterial hypertension in the spontaneously hypertensive rat (SHR) is associated with an abnormal Ca2+ homeostasis, compared with its normotensive control, the Wistar Kyoto rat (WKY). In particular, epithelial Ca2+ transport is perturbed, with intestinal absorption and renal tubular reabsorption being decreased in the adolescent and adult SHR. In the present study we examined Ca2+ uptake into isolated duodenal brush-border membrane vesicles (BBMV) in 12-14 week-old male rats. This uptake can be separated in a nonsaturable and a saturable component. The latter follows Michaelis-Menten kinetics. Vmax of this component was found to be significantly higher (p less than 0.05) in SHR than in WKY (0.58 +/- 0.19 versus 0.35 +/- 0.06 nmol/mg protein x 10 sec, mean +/- SD) whereas Km did not differ. Thus, the defect in the intestinal Ca2+ absorption previously identified in the SHR of this age is not due to a decrease in Ca uptake at the level of the duodenal brush-border membrane, but is most likely located in the baso-lateral membrane.     

The effect of tumor necrosis factor-alpha on D-fructose intestinal transport in rabbits

Tumor necrosis factor-alpha (TNF-alpha) is an important immunoregulatory cytokine involved in septic responses during bacterial infection. The aim of this study was to examine the effect of TNF-alpha on the transport of D-fructose across rabbit jejunum. A sepsis condition was evoked by intravenous administration of this cytokine and hematological and plasma parameters were analyzed and body temperature was recorded. D-Fructose transport was assayed in rabbit jejunum. Sugar absorption in TNF-alpha treated rabbits was lower than in control animals. TNF-alpha decreased both the mucosal-to-serosal transepithelial flux and the transport across brush border membrane vesicles of D-fructose. The number of D-fructose transporters (GLUT5) was analyzed by Western blot in an attempt to explain this inhibition. TNF-alpha treated animals had lower levels of GLUT5, indicating a reduction in the expression of GLUT5 protein and therefore in transport capacity. The inhibition could also be related with the secretagogue effect of TNF-alpha on the gut since the intracellular tissue water was affected and the absence of chloride ion in the incubation medium partly removed the cytokine inhibition on sugar intestinal transport in treated rabbits. Finally, in terms of possible mediators involved in the TNF-alpha effect, nitric oxide and prostaglandins appeared to play a role in the inhibition of D-fructose intestinal uptake.     

Adaptation of intestinal glucose transport in rats with diabetes mellitus occurs independent of hyperphagia.

Chronic diabetes enhances intestinal absorption of glucose and induces hyperphagia. We examined the enhanced intestinal absorption of glucose in ad libitum-fed rats with streptozocin-induced diabetes mellitus and compared these results with those obtained from pair-fed diabetic animals. Maximal transport capacity (Vmax) and carrier affinity (K0.5) were determined by measuring jejunal and ileal short circuit current (Isc) responses to varying concentrations of 3-O-methyl-D-glucopyranose and D-glucose. Pair-fed diabetic animals maintained the same body weight as animals fed ad libitum, although ad libitum-fed diabetic rats had an increased oral chow intake. Age-matched control rats maintained a constant jejunal and ileal Vmax and K0.5 throughout the study. Diabetic rats fed ad libitum demonstrated an enhanced Vmax and K0.5 in both jejunum and ileum. Pair feeding diabetic animals further enhanced jejunal Vmax while lowering jejunal K0.5 levels. In contrast, pair feeding diabetic animals delayed and blunted changes in ileal Vmax and prevented changes in ileal K0.5. In conclusion, signals other than those of hyperphagia regulate kinetic changes in glucose absorption during diabetes mellitus. Furthermore, these changes have differing effects on jejunum and ileum.     

Intestinal calcium transport in spontaneously hypertensive rats (SHR) and their genetically matched WKY rats

Calcium transport across the basolateral membranes of the enterocyte represents the active step in calcium translocation. This step occurs by two mechanisms, an ATP-dependent pump and a Ca2+/Na+ exchange process. These studies were designed to investigate these two processes in jejunal basolateral membrane vesicles (BLMV) of the spontaneously hypertensive rats (SHR) and their genetically matched controls, Wistar-Kyoto (WKY) rats. The ATP-dependent calcium uptake was stimulated several-fold compared with no ATP condition in both SHR and WKY, but no differences were noted between rate of calcium uptake in SHR and WKY. Kinetics of ATP-dependent calcium uptake at concentrations between 0.01 and 1.0 microM revealed a Vmax of 0.67 +/- 0.03 nmol/mg protein/20 sec and a Km of 0.2 +/- 0.03 microM in SHR and Vmax of 0.69 +/- 0.12 and a Km of 0.32 +/- 0.14 microM in WKY rats. Ca2+/Na+ exchange in jejunal BLMV of SHR and WKY was investigated in two ways. First, sodium was added to the incubation medium (cis-Na+). Second, Ca2+ efflux from BLMV was studied in the presence of extravesicular Na+ (trans-Na+). Both studies suggest a decreased exchange of calcium and Na+. Kinetic parameters of Na(+)-dependent Ca2+ uptake at concentrations between 0.01 and 1.0 microM exhibited Vmax of 0.05 +/- 0.01 nanmol/mg protein/5 sec and a Km of 0.21 +/- 0.13 microM in SHR and Vmax of 0.11 +/- 0.02 nanmol/mg protein/5 sec and a Km of 0.09 +/- 0.05 in WKY, respectively. These results confirm that the intestinal BLMV of SHR and WKY rats have two mechanisms for calcium extrusion, an ATP-dependent Ca2+ transport process and a Na+/Ca2+ exchange process. The ATP-dependent process appears to be functional in SHR; however, the Ca2+/Na+ exchange mechanism appears to have a marked decrease in its maximal capacity. These findings suggest that calcium extrusion via Ca2+/Na+ is impaired in the SHR, which may lead to an increase in intracellular calcium concentration. These findings may have relevance to the development of hypertension.     

Studies of arterial smooth muscle relaxation in younger (16-18 week) and older (28-31 week) spontaneously hypertensive rats

Both isometric and isotonic relaxation rates have previously been reported to be decreased in caudal arterial and mesenteric resistance arterial smooth muscle from 16- to 21-week-old spontaneously hypertensive rats (SHR) compared with muscle from age-matched normotensive Wistar-Kyoto rats (WKY). An increased maximum velocity of shortening (Vmax) and an increased shortening ability (delta Lmax) have also been reported for arterial smooth muscle from 16- to 21-week-old SHR. It has been suggested that both increased narrowing and prolonged narrowing of arteries contribute to the development of hypertension. However, SHR Vmax is not different from WKY Vmax when studying arterial muscle from older (28- to 31-week-old) rats. Thus increased arterial narrowing ability cannot be a contributing factor to the maintenance of hypertension. In this study the role of relaxation rate in the maintenance of hypertension was examined by comparing the relaxation rates of isometric and isotonic contractions of caudal arterial strips from 16- to 21-week-old SHR (n = 9) and WKY (n = 8) and from 28- to 31-week-old SHR (n = 7) and WKY (n = 5). While relaxation rates were lower for 16- to 21-week-old SHR compared with age-matched WKY preparations for both isometric and isotonic contractions, only isometric relaxation rates were found to be different in 28- to 31-week-old SHR compared with 28- to 31-week-old caudal arterial muscle (p less than 0.05). Vmax tended to normalize from a once-elevated velocity, while isometric relaxation rate remained decreased in SHR with ageing and (or) with progression of the hypertensive condition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary lipids modify the age-associated changes in intestinal uptake of fructose in rats

Because reduced nutrient absorption may contribute to malnourishment in the elderly, age and diet modulate fructose uptake in mice, and alterations in fructose uptake may be paralleled by changes in the abundance of fructose transporters, the objectives of this study were to determine 1) the effects of aging on fructose absorption in rats, 2) the effect of feeding diets enriched with saturated fatty acids (SFA) vs. polyunsaturated fatty acids (PUFA), and 3) the mechanisms of these age-and diet-associated changes. Male Fischer 344 rats aged 1, 9, and 24 mo received isocaloric diets enriched with SFA or PUFA. The uptake of (14)C-labeled D-fructose was determined in vitro using the intestinal sheet method. Northern and Western blot analyses and immunohistochemistry were used to determine the abundance of sodium-independent glucose and fructose transporters (GLUT)2 and GLUT5. When expressed on the basis of mucosal surface area, jejunal fructose uptake was increased in 9 and 24 mo compared with 1-mo-old animals fed SFA. PUFA-fed animals demonstrated increased fructose uptake at 24 mo compared with younger animals. Ileal fructose uptake was increased with SFA vs. PUFA in 9-mo-old rats but was reduced with SFA in 1- and 24-mo-old rats. Variations in GLUT2 and GLUT5 abundance did not parallel changes in uptake. These results indicate that 1) age increases fructose uptake when expressed on the basis of mucosal surface area, 2) age influences the adaptive response to dietary lipid modifications, and 3) alterations in fructose uptake are not explained by variations in GLUT2 or GLUT5.     

Ontogeny of mitochondrial calcium transport in spontaneously hypertensive (SHR) and WKY rats

The current studies were designed to investigate calcium uptake by intestinal jejunal sacs as well as in intestinal mitochondria of spontaneously hypertensive rats and their genetically matched WKY control rats. Kinetics of jejunal calcium uptake by jejunal sacs of adult SHR and WKY rats showed a significant decrease in Vmax of calcium uptake in SHR (227 +/- 24 versus 423 +/- 22 nmol.g tissue-1.3 min-1) compared to WKY rats P less than 0.001. To explore the intracellular handling of calcium by the intestinal mitochondria, calcium uptake was characterized by intestinal mitochondria before (suckling and weanling periods) and after (adult period) development of hypertension. Calcium uptake by intestinal mitochondria was driven by ATP in the presence of succinate as a respiratory substrate. Calcium uptake was stimulated several fold by the presence of ATP compared to no ATP conditions. Maximal calcium uptake occurred between 15-30 min and was significantly greater in adult SHR and WKY rats compared to corresponding values in weanling and suckling rats. Maximal ATP dependent calcium uptake in adult, weanling and suckling WKY rats was significantly greater compared to corresponding mean values in each age group in SHR (P less than 0.001). Oligomycin (10 micrograms/mg protein) inhibited calcium uptake partially. Ruthenium red (0.25 microM), 1 mM sodium azide and 0.5 mM dinitrophenol inhibited calcium uptake by more than 80% in both SHR and WKY rats. Kinetic parameters for ATP stimulated calcium uptake at 10 s revealed a Vmax of 0.56 +/- 0.6, 3.46 +/- 0.23 and 3.95 +/- 0.52 nmol/mg protein/10 s in suckling, weanling and adult WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreased velocity of shortening in arterial smooth muscle from older (28- to 31-week-old) spontaneously hypertensive rats

An increased maximum velocity of shortening (Vmax) and increased shortening ability (delta Lmax) have been reported for caudal arterial smooth muscle from 16- to 18-week-old spontaneously hypertensive rats (SHR) compared with age-matched Wistar-Kyoto (WKY) control rats. It is known that hypertension results in hypertrophy of vascular smooth muscle. It is plausible that the faster Vmax of 16- to 18-week-old SHR arterial smooth muscle may slow down with age due to hypertrophy. The force-velocity (F-V) study done previously on caudal arterial strips from 16- to 18-week-old SHR and WKY rats was repeated on preparations from 28- to 31-week-old rats. An electromagnetic muscle lever was employed in recording force-velocity data. Analysis of these data revealed that the 28- to 31-week-old SHR (n = 7) mean F-V curve was not different from the 28- to 31-week-old WKY (n = 5) mean F-V curve (p greater than 0.05), and the shortening ability of 28- to 31-week-old SHR arterial muscle was significantly depressed compared with 28- to 31-week-old WKY arterial muscle (p less than 0.01). In conclusion, (i) although Vmax is faster in younger (16- to 18-week-old) SHR compared with age-matched WKY caudal arterial smooth muscle, SHR Vmax is not different from WKY Vmax in the older (28- to 31-week-old) rats. (ii) Shortening ability is greater in 16- to 18-week-old SHR caudal arterial strips compared with 16- to 18-week-old WKY strips, but is significantly depressed in 28- to 31-week-old SHR compared with 28- to 31-week-old WKY preparations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ion transport in erythrocytes of Prague hypertensive rat

The Prague hypertensive rat is a unique strain exhibiting genetic hypertension in which a hypertensive line (PHR) was bred in parallel with a normotensive one (Prague normotensive rat--PNR) from the same parental pair. Sodium efflux from Na(+)-loaded erythrocytes into Mg2(+)-sucrose medium was measured in these two strains as well as in spontaneously hypertensive rats (Okamoto-Aoki, SHR) and in normotensive outbred Wistar rats. Kinetic parameters--maximal velocity and apparent dissociation constant (reflecting the affinity for internal sodium)--were calculated. It was found that PHR as well as SHR had a higher Na+ leak and a decreased activity of the ouabain-sensitive Na+ transport as compared to Wistar rats. Furosemide-sensitive Na+ transport was substantially lower in erythrocytes of both hypertensive strains (PHR and SHR) than in the respective normotensive strains (PNR and Wistar).     

Magnesium uptake by intestinal brush-border membranes of spontaneously hypertensive rats.

Magnesium uptake by intestinal brush-border membranes (BBM) was studied in duodenal and jejunal vesicles of the spontaneously hypertensive rat (SHR) and normotensive control, the Wistar-Kyoto (WKY) rat. In the duodenum, no statistical difference was evidenced between the two types of rats. By contrast, initial rates of magnesium uptake in jejunal vesicles were lower in SHR (5.4 +/- 2.1 nmol/mg protein x 10 sec) in comparison to WKY rats (11.0 +/- 2.5 nmol/mg protein x 10 sec) at a magnesium concentration of 1 mM (P less than 0.01). In jejunal BBM, kinetic analysis of magnesium uptake showed three components in WKY rats, with one being diffusional. In SHR, only two components were seen, with the diffusional one being absent. The two saturable components showed Vmax of 6.5 +/- 1.3 and 26.2 +/- 6.0 nmol/mg protein x 10 sec and apparent Km of 0.22 +/- 0.12 mM and 1.9 +/- 0.4 mM in WKY rats, and Vmax of 10.9 +/- 3.5 and 14.8 +/- 5.9 nmol/mg protein x 10 sec and apparent Km of 0.43 +/- 0.23 mM and 1.3 +/- 0.2 mM in SHR. Only the component with the lowest apparent affinity appeared statistically different in SHR as compared with WKY rats for both Vmax and apparent Km (P less than 0.05). Time course evolution of magnesium uptake in jejunal BBM indicated, by extrapolation at zero time, that 2.5 and 5.1 nmol magnesium/mg protein in SHR and WKY rats, respectively, would be in the bound state. The study of the influence of medium osmolarity on 60-min magnesium uptakes was also indicative of a smaller binding compartment in jejunal BBM of SHR (3.70 and 8.26 nmol/mg protein in SHR and WKY rats, respectively); at the four osmolarities assayed, the 60-min uptakes were significantly lower in SHR as compared with WKY rats (P less than 0.01). From 60-min glucose uptakes, a smaller volume of jejunal BBM vesicles was determined for SHR as compared with WKY rats (0.34 +/- 0.06 and 0.63 +/- 0.17 microliter/mg of protein in SHR and WKY rats respectively, P less than 0.05), this volume being significantly augmented by the presence of 1 mM MgCl2 (0.48 +/- 0.05 and 1.27 +/- 0.02 microliter/mg of protein in SHR and WKY rats respectively, P less than 0.01). These results suggest that magnesium uptake and binding by jejunal BBM are altered in SHR in comparison to WKY rats, implying a possible role of the small intestine in the abnormalities of magnesium metabolism in genetic hypertension.     

自发性高血压大鼠多组织炎症状态

高血压是一种慢性血管性疾病,易累及肾、肝、心、脑等组织,引起脑卒中和心、肾损害等并发症.本研究对高血压时肾、肝、心、脑等组织的炎症状态进行了观察.实验采用自发性高血压大鼠(spontaneously hypertensive rat,SHR)和正常血压的Wistar-Kyoto(WKY)大鼠,用RT-PCR和Western blot法观察肾、肝、心、脑等组织炎症相关因子IL-1p、TNFα、ICAM-1、iNOS、C/EBPδ和PPARγ的基因表达;紫外分光光度法观察蛋白质羰基化水平和FRAP法检测组织总抗氧化能力.结果显示(1)SHR组织炎症相关因子表达较对照WKY增强,除IL-1βmRNA在肝和脑的增加不明显外,其余均有显著性差异(P＜0.05);(2)SHR和WKY大鼠肾、心、脑蛋白质羰基化水平(nmol/mg蛋白)分别为8.93±1.08和2.27±0.43、2.23±0.23和0.17±0.02、13.42±1.10和5.72±1.01,SHR明显增加(P＜0.05);而肝脏蛋白质羰基化水平无明显变化;(3)SHR肾、肝、心、脑总抗氧化能力水平显著低于WKY大鼠(P＜0.05).以上结果表明,SHR多个组织(肾、肝、心和脑)均存在炎症因子被诱导和氧化应激反应等明显的炎症状态,提示炎症可能在高血压及其并发症的病理改变中起重要作用.     

Low Activity of Angiotensin-Converting Enzyme in Cerebral Microvessels of Young Spontaneously Hypertensive Rats

Angiotensin-converting enzyme (ACE) activity was measured in microvessels prepared from cerebral cortices of 4-week-old spontaneously hypertensive rats (SHR). The Vmax value of the ACE activity in the cerebral microvessels of SHR was lower than that of Wistar Kyoto controls of the same age by 25% without difference in Km value for substrate. The low activity of ACE in the cerebral microvessels of young SHR indicates that in this animal model of hypertension the function of ACE is genetically altered in the cerebral microvessels, which may be correlated with the alteration of the cerebral microcirculation and pathogenesis of hypertension.     

Dexamethasone and GLP-2 administered to rat dams during pregnancy and lactation have late effects on intestinal sugar transport in their postweaning offspring

Intestinal function in young animals is influenced by maternal factors, such as alterations in the maternal diet. Glucagon-like peptide 2 (GLP-2) enhances intestinal growth and absorption in mature animals. Glucocorticosteroids induce intestinal maturation in neonates and increase sugar uptake in adult animals. It is not known if maternally administered GLP-2 or glucocorticosteroids have persistent effects on intestinal transport in the offspring. This study was undertaken to determine (1) the influence of maternal GLP-2, dexamethasone (DEX) and GLP-2+DEX on intestinal sugar uptake in postweaning offspring and (2) if alterations in uptake are due to variations in intestinal morphology, sugar transporter abundance or the abundance of selected signals. Nursing rat dams were treated during pregnancy and lactation with GLP-2 (0.1 mug/g per day sc), DEX (0.128 microg/g per day sc), GLP-2+DEX or placebo. The offspring were sacrificed 4 weeks after weaning, and glucose and fructose uptake was determined using an in vitro intestinal ring uptake technique. sodium-dependent glucose transporter, glucose transporter (GLUT) 5, GLUT2, sodium potassium adenosine triphosphatase and selected signals were assessed by immunohistochemistry. The treatments did not affect body weights or intestinal morphology. GLP-2 and GLP-2+DEX increased jejunal fructose uptake, and GLP-2+DEX increased the jejunal and ileal maximal transport rate for glucose uptake. Protein kinase B and mammalian target of rapamycin abundance were also increased, while transporter abundance was unchanged. We speculate that these alterations in sugar uptake may be due to changes in the intrinsic activity of the transporters mediated by the phosphatidylinositol-3-kinase pathway. These alterations in uptake may have nutritional implications for the offspring of mothers who may be treated with GLP-2 or glucocorticosteroids.     

Force-velocity relationships in hypertensive arterial smooth muscle

Increased total peripheral resistance is the cardinal haemodynamic disorder in essential hypertension. This could be secondary to alterations in the mechanical properties of vascular smooth muscle. Adequate study has not been made of the force-velocity (F-V) relationship in hypertensive arterial smooth muscle. Increased shortening in arterial smooth muscle would result in greater narrowing of arteries. The objectives of this investigation were to see if there is (i) increased shortening or increased maximum change in muscle length (delta Lmax where L stands for muscle length), (ii) an increased maximum velocity of shortening (Vmax) measured in l omicron per second where l omicron is the optimal muscle length for tension development, and (iii) a difference in maximum isometric tension (P omicron) developed in spontaneously hypertensive rat (SHR; N = 6) compared with normotensive Wistar Kyoto rat (WKY;N = 5) caudal artery strips. An electromagnetic muscle lever was employed in recording force-velocity data. Analysis of these data revealed the following: (a) the SHR mean P omicron of 6.21 +/- 1.01 N/cm2 was not different from the mean WKY P omicron of 6.97 +/- 1.64 N/cm2 (p greater than 0.05); (b) the SHR preparations showed greater shortening for all loads imposed; (c) the SHR Vmax of 0.016 l omicron/s was greater than the WKY Vmax of 0.013 l omicron/s (p less than 0.05). This study provides evidence that while hypertensive arterial smooth muscle is not able to produce more force than normotensive arterial smooth muscle, it is capable of faster and greater shortening. The latter could result in increased narrowing of hypertensive arteries and increased blood pressure.     

Acute arterial hypertension inhibits proximal tubular fluid reabsorption in normotensive rat but not in SHR

The effect of acute arterial hypertension on proximal tubular fluid reabsorption was investigated in Sprague-Dawley rats and spontaneously hypertensive rats (SHR) by measuring proximal tubular flow with a nonobstructive optical method. Under control conditions, spontaneous tubular flow was oscillating at 0.02-0.03 Hz in Sprague-Dawley rats. Acute hypertension induced an immediate increase of mean tubular flow (50% increase after 20 min of hypertension) and augmentation of oscillatory amplitude. Acute hypertension did not alter single-nephron blood flow as measured by laser-Doppler velocimetry (n = 12), suggesting that the increase of tubular flow was due to inhibition of reabsorption but not increase of filtration. By contrast, spontaneous tubular flow was fluctuating aperiodically in SHR. Acute hype tension did not induce a continuous increase of tubular flow or an increase in amplitude of fluctuations (n = 15). When apical Na(+)/H(+) exchange activity of proximal tubule was monitored, acute hypertension did not alter the activity in SHR (n = 8), while similar procedures had been shown to inhibit apical Na(+)/H(+) exchange activity of proximal tubules by more than 40% in Sprague-Dawley rats. These observations suggest that acute hypertension inhibits proximal tubular fluid reabsorption by inhibiting apical Na(+)/H(+) exchange activity in Sprague-Dawley rats and that this mechanism is impaired in SHR.     

Na+--K+-adenosine triphosphatase and some oxidoreductases in the kidney of rats with spontaneous hypertension]

The activities of the Na+--K+-ATPase, succinic dehydrogenase (SDH/, lactic dehydrogenase (LDH/ and glucose-6-phosphat dehydrogenase (G-6-PDH/ were studied in the cortex outer and inner medulla of the kidneys of rats with spontaneous hypertension (SHR) and were compared with those of control normotensive Wistar rats. The SHR aged 6--8 weeks had durint the prehypertensive and the early hypertensive stage the same enzymatic activities as control rats. Rats with a steady SH aged 16-22 weeks had low specific activity of the, Na+--K+-ATPase, SDH and LDH in the outer medulla. The latter can be associated with decreased intensity of the energy metabolism and a reduction of the active sodium transport in the ascending limb of the loop of Henle in the SHR rats and cold cause the phenomenon of exaggerated natriuresis characteristic of hypertension.