ALTERATIONS IN CEREBROSPINAL FLUID SODIUM AND OSMOLALITY IN RATS DURING ONE-KIDNEY, ONE-WRAP RENAL HYPERTENSION

Measurements of plasma and cerebrospinal fluid (CSF) sodium and osmolality were made throughout the course of one-kidney, one-wrap Grollman renal hypertension. Although the plasma sodium and osmolality did not rise after 28 days, CSF sodium and osmolality was increased significantly at 3 days postwrap. As a result, the CSF to plasma ratio for both sodium and osmolality was significantly elevated during the initial postwrap period. These observations suggest that an increase in CSF sodium may provide an initiating stimulus for an elevated arterial pressure in one-kidney, one-wrap renal hypertension.     

EFFECT OF SODIUM INTAKE ON INTRAERYTHROCYTE SODIUM CONCENTRATION IN NORMOTENSIVE SUBJECTS AND PATIENTS WITH UNTREATED MILD HYPERTENSION

1. The effect of changing sodium intake for 2 weeks was studied. Twelve nor-motensive subjects and five patients with mild essential hypertension were given two different levels of sodium intake for 2 weeks. 2. Overall there was no significant rise in blood pressure but all patients with hypertension had a rise in blood pressure as they went from a low to a high sodium intake. 3. Plasma sodium was not altered but red cell sodium concentration was higher on the high sodium intake. This effect was observed in both normotensive and hypertensive people. 4. Alterations observed in cell sodium concentration provide support for the hypothesis that increased dietary intake of sodium may induce hypertension by causing changes in cellular transport systems.     

金牡蛎对大鼠高脂血症脂肪肝的防治作用

探讨金牡蛎、牛磺酸对肥胖性高脂血症脂肪肝的防治作用。金牡蛎和牛磺酸在适当减轻造模的物体重的同时,显著降低共血脂和肝组织脂肪含量,并显著改善肝组织病理学变化,结论：金牡蛎及其提取物牛磺酸可有效防治大鼠实验性高脂血症和脂肪肝。     

SODIUM PREFERENCE AND EXCRETION IN SPONTANEOUSLY HYPERTENSIVE RATS ON VARIOUS DIETS

Stroke-prone spontaneously hypertensive rats (SHRSP) and stroke-resistant SHR (SHRSR) exhibited an increased preference for a 2% NaCl solution, relative to water, in comparison with normotensive Wistar-Kyoto (WKY), but the preference was lost quickly in SHRSP with unbroken exposure. Neither a high protein diet (50% fish protein) nor a low protein diet (5% protein) changed the salt water preference in SHRSR and the former abolished the preference more quickly in SHRSP. The fish protein diet, however, increased the ratio of urinary sodium excretion to dietary sodium intake in the first three days of exposure to a high salt intake in all groups. Results from this experiment suggest that an increased dietary protein intake can facilitate sodium excretion and may possibly ameliorate the adverse effect of a high sodium diet.     

川芎哚大鼠体内代谢转化研究

目的　研究川芎有效成分川芎哚在大鼠体内的代谢转化。方法　分别ig川芎哚和［2-¹⁵N］川芎哚后,尿样经酶水解、碱化、有机溶剂提取。有机相(碱性和中性部分)经浓缩并硅烷化;水相经酸化、提取(提取物为酸性水溶部分)并硅烷化,用GC-MS测定。结果　在碱性和中性提取物中,检出原型川芎哚及其一种代谢物;在酸性水溶性提取物中,检出川芎哚的另两种代谢物。结论　川芎哚体内代谢途径可能是川芎哚羟基化和川芎哚羟甲基的氧化。     

COMPARISON OF THE VASCULAR AND GLOMERULAR CHANGES IN AORTIC-LIGATURE AND DOCA-SALT HYPERTENSION

1. Animals and histology from two previous investigations were used to test the hypothesis that a similar elevation in blood pressure may result in a different sequence of pathological changes in different experimental models of hypertension, DOCA-salt and aortic-ligature hypertension. 2. To asses differences in morphological parameters, individual animals in the two groups were paired (n = 12) for the same level of blood pressure at sacrifice. 3. Vascular damage was significantly less in the DOCA-salt group (P less than 0.01). Glomerular lesions however were more severe in the DOCA-salt group. In rats with aortic-ligature hypertension significantly fewer glomeruli had fibrinoid and/or crescents than in DOCA-salt rats (P less than 0.001). There were fewer glomeruli with epithelial cell droplets (ECD) and fewer ECD per glomerulus in aortic-ligature when compared with DOCA-salt hypertension (P less than 0.001, P less than 0.001, respectively). 4. This study highlights the significance of factors other than blood pressure per se in producing vessel and glomerular lesions in experimental hypertension.     

CHANGE IN BLOOD PRESSURE IN RELATION TO CHANGE IN NUTRIENTS EFFECTED BY MANIPULATION OF DIETARY SODIUM AND POTASSIUM

1. As part of a study investigating the effect of dietary alterations of sodium and potassium intake on blood pressure, the changes in nutrients that occurred with dietary intervention were determined. 2. Mild hypertensive subjects were randomized to one of four dietary intervention groups: control; high potassium; low sodium; low sodium, high potassium. The changes in nutrients in each diet group were assessed by dietary history and five repeat 24 h dietary recalls. Assessment was validated by measurement of urinary nitrogen excretion and urinary electrolytes. 3. The three dietary intervention groups experienced a fall in blood pressure (systolic: 4.4 +/- 1.0 mmHg, P less than 0.005; diastolic: 3.3 +/- 0.7 mmHg, P less than 0.001), greater than that observed in the control group. 4. The only significant dietary change across all diet groups was a reduction in the dietary sodium/potassium ratio, which was significantly less than that of the control group. The only other nutrient to differ from the control in all groups was fat intake, which was reduced. 5. In the control group there was a small but significant decrease in energy, fibre, protein, carbohydrate, potassium and magnesium intake. In the high potassium group there was a significant increase in fibre, carbohydrate, potassium, magnesium, and a decrease in calcium intake. In the low sodium group there was a decrease in energy intake with a subsequent reduction in all nutrients except alcohol. In the low sodium, high potassium group there was a significant reduction in dietary sodium and protein and an increase in fibre, carbohydrate, potassium and magnesium. 6. The reduction of the dietary sodium/potassium ratio correlated with a reduction in the urinary sodium/potassium ratio. This was the best predictor for change in diastolic pressure in all groups, suggesting that reduction in the sodium/potassium ratio contributed to the fall in blood pressure. 7. Reduction of sodium intake and increase in potassium intake by dietary means caused a reduction in blood pressure which does not appear to be due to alteration of other measured dietary constituents.     

FISH PROTEIN-RICH DIET ATTENUATES HYPERTENSION INDUCED BY DIETARY Ng-NITRO-L-ARGININE IN NORMOTENSIVE WISTAR-KYOTO RATS

1. Dietary 0.023%N^G-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthesis, induced hypertension in normotensive Wistar-Kyoto rats (WKY). This hypertension was significantly attenuated in WKY given a fish protein-rich diet. 2. The supplement of 2% L-arginine given in a standard diet or a diet containing 3% taurine for drinking did not significantly affect the development of hypertension induced by L-NNA in WKY. 3. WKY which received the standard diet mixed with 10% urea and 0.023% L-NNA had significantly attenuated hypertension compared with WKY receiving the standard diet mixed with 10% kaolin and 0.023% L-NNA. 4. These results suggest that the attenuation of hypertension in L-NNA-treated WKY rats given a fish protein rich diet may be partly caused by urea, a metabolic end-product of protein.     

DEVELOPMENT OF HYPERTENSION AND PROTEINURIA WITH AGE IN FAWN-HOODED RATS

Blood pressure and urinary protein excretion were monitored in male fawn hooded rats (FH rats) from 8 until 46 weeks of age. Mild hypertension was already observed at 8 weeks of age. Between the age of 5 and 7 months the blood pressure rose steeply to a plateau of about 200 mmHg. Then it stabilized and the level was different for animals of different litters but similar for littermates. Concomitantly with the increase in blood pressure, proteinuria increased with age. Examination of renal tissue at 6.5 and 9 months of age revealed the presence of focal and segmental glomerulosclerosis. The renal changes were not accompanied by gross alterations in renal function. In animals with severe hypertension pronounced proteinuria occurred, and they appeared to form a distinct class. In some of the animals intermittent haematuria occurred. Persistent haematuria, however, had a bad prognosis. There was no glucosuria. Water intake of the animals with severe hypertension was increased. Water intake of young FH rats was found to be of value for predicting the severity of the hypertension in these animals at a later age. It is concluded that the FH rat is an example of a non-inbred rat strain showing spontaneous hypertension. This hypertension may result from an aberrant renal water handling and/or volume regulation.     

SODIUM BALANCE AND PLASMA RENIN ACTIVITY DURING THE DEVELOPMENT OF TWO-KIDNEY GOLDBLATT HYPERTENSION IN RATS

1. In two experiments severe hypertension (systolic blood pressure 180 mmHg) was induced in rats by constricting one renal artery with a silver clip (two-kidney, one clip hypertension; 2KIC). Blood pressure, plasma renin activity (PRA) and body weight were measured for 35 days after clipping. Plasma sodium concentration and carcass sodium content were measured at the conclusion of the experiment. To determine the relationship between sodium intake, PRA and the development of severe hypertension, half of the rats were given a normal diet and water to drink; the other half were given a low sodium diet and 0-9% saline to drink. 2. In both experiments, two patterns of responses were observed. Group (1) had reduced growth rate, and marked elevation of PRA. Some, but not all of these animals had histological evidence of malignant nephrosclerosis in the untouched kidney. In the other group (11), weight gain was normal and PRA was normal or only slightly elevated. 3. Group 1 animals drinking saline, had raised carcass sodium levels, whereas those drinking water had no increase in carcass sodium. 4. The results confirm that hypertension in the 2KIC model is not always associated with a raised PRA. 5. The coexistence of a raised PRA and increased total body sodium suggests that the PRA does not rise as a result of sodium depletion in this model.     

EFFECTS OF HIGH SALT INTAKE ON CONTROL OF HINDLIMB VASCULAR RESISTANCE BY ARTERIAL BROREFLEX AND VAGAL AFFERENTS IN SPONTANEOUSLY HYPERTENSIVE RATS

1. This study aimed to examine whether a high salt diet alters control of vascular resistance by arterial baroreflex and vagal afferents in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). 2. SHR and WKY aged 8 weeks were fed either high (8%) or normal salt (0.4%) diet for 4 weeks. Arterial baroreflex control of hindlimb vascular resistance was assessed by examining reflex-induced vasodilation and vasoconstriction in response to phenylephrine and nitroprusside, respectively, in the constant-flow perfused hindlimb of urethane-anesthetized rats. 3. Tonic influence of the cardiopulmonary vagal afferents was evaluated by examining the effects of vagotomy on hindlimb vascular resistance and on the gain of arterial baroreflex control of hindlimb vascular resistance. 4. The gain of the arterial baroreflex control of hindlimb vascular resistance in response to both phenylephrine and nitroprusside were not significantly different between SHR receiving high and normal salt diets, and between WKY receiving high and normal salt diets. 5. Vagotomy increased hindlimb vascular resistance in all four groups of rats. However the magnitude of the increase in hindlimb vascular resistance was less in SHR on a high salt diet than those in SHR on a normal salt diet but similar between the two groups of WKY. Vagotomy increased the slope of arterial baroreflex control of hindlimb vascular resistance in SHR receiving a normal salt diet and the two groups of WKY but not in SHR receiving a high salt diet. 6. These results suggest that a high salt diet attenuates the inhibitory influence of vagal afferents on the control of vascular resistance in SHR but not in WKY, while the arterial baroreflex control of vascular resistance is preserved during high salt diet in both SHR and WKY.     

BLOOD PRESSURE, SALT TASTE AND SODIUM EXCRETION IN RATS EXPOSED PRENATALLY TO HIGH SALT DIET

Blood pressure, sodium excretion and salt taste were examined in Sprague Dawley (SD) and Munich Wistar (MW) rats exposed prenatally to either a high salt (2.3% NaCl w/w) or control diet. There was no significant difference in blood pressure at 2, 6 or 12 months between high salt and control groups in either strain. Similarly there was no significant difference in sodium excretion following a saline load by gavage (150 mmol/l, 1.5% BW). Munich Wistar rats which received high salt diet prenatally exhibited a reduced saline preference when offered a choice between water and 150 mmol/l NaCl as drinking fluid. There was no significant difference in saline preference between Sprague Dawley rats which received the high salt or control diet. Prenatal exposure to high salt diet failed to alter the blood pressure or excretion of a salt load in either SD or MW rats. In MW rats but not SD high salt diet prenatally resulted in a reduced saline preference at 3 months of age.     

EFFECT OF PARATHYROIDECTOMY ON DEVELOPMENT OF HYPERTENSION AND ATRIAL RESPONSIVENESS IN SPONTANEOUS HYPERTENSIVE RATS

1. In order to further clarify the relationships between parathyroid function and development of hypertension, the effects of parathyroidectomy (PTX) on blood pressure and on responsiveness of atria isolated from spontaneous hypertensive rats (SHR) were examined. 2. PTX was carried out in 6-week-old SHR and normotensive Wistar rats. The experiments were performed 2 weeks after surgery. 3. PTX reduced the plasma calcium concentration and decreased atrial calcium content in SHR. On the other hand, basal contractile force and beat frequency of isolated atria were higher in PTX SHR than in sham-operated SHR. In response to cumulative addition of isoprenaline, atria from PTX SHR displayed diminished inotropic and chronotropic responses compared with sham-operated SHR. Similar results were obtained in atria isolated from Wistar rats. When calcium sensitivity was studied in atria from Wistar rats, basal and isoprenaline-induced maximum contractile forces were higher in PTX group than in the sham-operated group. Nevertheless, basal and isoprenaline-induced maximum contractile forces, determined at the respective plasma ionized calcium concentration of PTX and sham-operated groups (0.83 and 1.22 mmol/L), were not significantly different. 4. Our results do not favour a role for alteration in atrial activity as a causal mechanism in delayed development of experimental genetic hypertension after parathyroidectomy.     

INFLUENCE OF BRADYKININ ON BLOOD PRESSURE REGULATION OF SPONTANEOUSLY HYPERTENSIVE RATS MAINTAINED ON DIFFERENT SODIUM INTAKES

1. The role of circulating bradykinin in blood pressure regulation was studied in conscious spontaneously hypertensive rats utilizing the competitive antagonist of bradykinin B4162. 2. This antagonist was administered at a bolus dose (400 micrograms i.v.) known to block the hypotensive effect of exogenous bradykinin for at least 2 min. The rats were maintained for 10 days either on a low or a high sodium intake. 3. The antagonist of bradykinin significantly increased blood pressure only in salt-depleted rats. In other rats kept on a low or a high sodium intake, dose-response curves to exogenous bradykinin were established. Dietary sodium had no influence on the blood pressure-lowering effect of bradykinin. 4. These data therefore suggest that circulating bradykinin may be involved in the blood pressure control of spontaneously hypertensive rats when the renin-angiotensin system is stimulated by salt depletion.     

EFFECT OF DIETARY SALT LOADING AND HIGH-CALCIUM DIET ON VASCULAR SMOOTH MUSCLE RESPONSES AND ENDOTHELIUM FUNCTION IN RATS

1. The present study examined the effects of concurrent manipulation of dietary calcium and salt on contractile responses of vascular smooth muscle (VSM) and endothelial function of aortic rings from Sprague-Dawley rats. 2. Salt loading enhanced the contractile response of the aortic rings to noradrenaline (NA), an effect that was blunted by a high calciu. intake. 3. Removal of the endothelium and incubation of aortic rings in physiological salt solution containing methylene blue increased the sensitivity of the rings t. NA. 4. The increase in the sensitivity of aortic rings induced by endothelium removal was more pronounced in aortic rings from salt-loade. rats. 5. Acetylcholine caused similar degrees of relaxation in all experimental groups, but the relaxation to histamine was smalle. (P < 0.05) in salt-loaded rats than in other groups of rats; however, after removal of the endothelium, the contractile response to histamine was higher in salt-loaded rats. 6. The results indicate that the hypersensitivity of isolated aortic rings to agonists, as observed in salt-loaded rats, is due to altered responses of the VSM and not as a result of changes in the endothelium. In addition, salt loading tends to increase the synthesis of endothelium-dependent relaxing factor. The ability of salt loading to enhance the contractile responses of VSM to agonists can be prevented by supplementing the diet with high calcium.     

SODIUM DETECTION THRESHOLD AND PREFERENCE FOR SODIUM CHLORIDE IN HUMANS ON HIGH AND LOW SODIUM DIETS

Sodium detection threshold and preference for sodium chloride was examined in human volunteers on 2 week periods of high and low salt diets. There was no significant difference in salivary electrolytes or sodium detection threshold between the high and low salt diet periods. Sodium preference, defined as the final sodium concentration of unsalted tomato juice following the ad libitum addition of NaCl, was significantly less on the low salt diet when compared to the high salt period. These results suggest that short periods of dietary salt modification can result in marked shifts in preference for NaCl in the absence of changes in the physiological parameters measured.     

A RANDOMIZED CONTROL TRIAL OF A VEGETARIAN DIET IN THE TREATMENT OF MILD HYPERTENSION

The effect of an ovo-lacto-vegetarian (OLV) diet on blood pressure was assessed in a randomized, controlled, crossover trial in 58 mild untreated hypertensive subjects recruited from the Perth Centre for the 1983 NHF Risk Factor Prevalence Survey. Subjects were randomly allocated to one of three groups; the first maintained their usual diet throughout 12 weeks; the other two were given an OLV diet for either the first or second 6 weeks of the 12-week trial. Introduction of an OLV diet was associated with a significant fall in systolic blood pressure, on average of the order of 5 mmHg, which was unrelated to change in urinary sodium, potassium or body weight. It was concluded that a vegetarian diet may have an adjunctive role in control of mild hypertension, but that in view of likely problems with acceptability those dietary components responsible for the blood pressure differences need to be identified.     

TOTAL BODY SODIUM IN IMMATURE SPONTANEOUSLY HYPERTENSIVE AND WISTAR KYOTO RATS

Total body sodium of male and female spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats was estimated weekly during the first 8 weeks of life by measuring exchangeable sodium (ENa). Blood pressure and sodium intake was measured from weeks 4 to 8. SHR had significantly higher blood pressure and sodium intake than WKY from 4 to 8 weeks of age. ENa was higher in SHR than WKY throughout the first 8 weeks of life. Relative sodium retention was observed in SHR during weeks 5 to 8 despite a significant rise in SHR blood pressure and fall in sodium intake. These findings suggest a change in the renal pressure/natriuresis relationship at this age in the SHR.     

EFFECTS OF SODIUM RESTRICTION ON CARDIAC 3,4-DIHYDROXYPHENYLETHYLENE GLYCOL AND CATECHOLAMINE LEVELS IN RATS

1. The effects of low or high sodium intake for 4 weeks on cardiac catecholamines and 3,4-dihydroxyphenylethylene glycol (DHPG) levels were studied in adult female Wistar rats. 2. Rats receiving the low sodium diet had significantly higher plasma renin activity than rats receiving the high sodium diet. 3. Dopamine concentrations in both the right and left ventricle were significantly higher in the low salt compared with the high salt rats, but noradrenaline, adrenaline and DHPG levels did not differ significantly between the two groups. 4. These data do not support previous reports that sodium restriction reduces cardiac noradrenaline release, but suggest that alterations in sodium intake may influence cardiac noradrenaline metabolism.