Renal dopamine and noradrenaline excretion during CNS-induced natriuresis in spontaneously hypertensive rats: influence of dietary sodium

Abnormalities in dopamine (DA) and noradrenaline (NA) activities and sodium handling may be involved in the pathogenesis of hypertension. The present study was designed to investigate whether any differences exist between normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in urinary excretion of DA, NA and sodium after 15 weeks on a low, medium or high sodium diet and during a subsequent elevation of the cerebroventricular fluid sodium concentration (CNS-induced natriuresis). Seven features were noted: (1) Basal sodium and DA excretion after the diet regimen was correlated to the dietary sodium content in both strains, except that sodium and DA excretion in SHR showed no further increase after the high sodium diet over and above that after medium sodium diet. (2) For any given sodium diet, SHR excreted more DA and NA as compared with WKY. (3) Blood pressure in SHR, as opposed to that in WKY, was higher after medium and high sodium diet than after low sodium diet. (4) During CNS-induced natriuresis NA excretion decreased or remained unchanged in WKY, but increased in SHR. (5) The DA/NA excretion ratio during CNS-induced natriuresis increased in WKY while decreased in SHR, which would not favour a natriuretic/vasodilatory response in the latter. (6) The ability of SHR to respond with CNS-induced natriuresis was attenuated after high sodium diet. (7) The magnitude of CNS-induced natriuresis was in both strains correlated to the sodium diet; the higher the dietary sodium content, the greater the natriuretic response. In conclusion, the study shows some clear differences in the catecholamine and sodium handling between WKY and SHR which may be involved in the pathogenesis of hypertension in SHR. Furthermore, increased sodium in the diet sensitizes the brain and kidney to increase the ability to respond with natriuresis for a given sodium stimulus.     

Renal dopamine and noradrenaline excretion during CNS‐induced natriuresis in spontaneously hypertensive rats: influence of dietary sodium

Abnormalities in dopamine (DA) and noradrenaline (NA) activities and sodium handling may be involved in the pathogenesis of hypertension. The present study was designed to investigate whether any differences exist between normotensive Wistar–Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in urinary excretion of DA, NA and sodium after 15 weeks on a low, medium or high sodium diet and during a subsequent elevation of the cerebroventricular fluid sodium concentration (CNS‐induced natriuresis). Seven features were noted: (1) Basal sodium and DA excretion after the diet regimen was correlated to the dietary sodium content in both strains, except that sodium and DA excretion in SHR showed no further increase after the high sodium diet over and above that after medium sodium diet. (2) For any given sodium diet, SHR excreted more DA and NA as compared with WKY. (3) Blood pressure in SHR, as opposed to that in WKY, was higher after medium and high sodium diet than after low sodium diet. (4) During CNS‐induced natriuresis NA excretion decreased or remained unchanged in WKY, but increased in SHR. (5) The DA/NA excretion ratio during CNS‐induced natriuresis increased in WKY while decreased in SHR, which would not favour a natriuretic/vasodilatory response in the latter. (6) The ability of SHR to respond with CNS‐induced natriuresis was attenuated after high sodium diet. (7) The magnitude of CNS‐induced natriuresis was in both strains correlated to the sodium diet; the higher the dietary sodium content, the greater the natriuretic response. In conclusion, the study shows some clear differences in the catecholamine and sodium handling between WKY and SHR which may be involved in the pathogenesis of hypertension in SHR. Furthermore, increased sodium in the diet sensitizes the brain and kidney to increase the ability to respond with natriuresis for a given sodium stimulus.     

The intestinal tract and the pathophysiology of arterial hypertension: an experimental study on Dahl rats

Salt depleted rabbits and humans excrete an oral sodium load more quickly via the kidneys than an intravenous one. This has been ascribed to the presence of a sodium sensor in the gastrointestinal tract which in some way can influence renal function. The purpose of this study was to investigate this response in the Dahl rats. Renal and faecal sodium excretion was followed in the two strains of rats (normotensive, saltresistant (SR/Jr) and hypertensive, saltsensitive (SS/Jr) rats). After 4 days on a low salt diet they were given NaCl(l.5 mmol kg^-1 body wt) either by gavage or intravenously. SR/Jr rats showed an increased renal sodium excretion both after oral and intravenous sodium repletion. The excretion was 2–3 times greater after the oral than after the intravenous administration. The SS/Jr rats augmented their renal sodium excretion only after the oral load, although the sodium excretion was significantly less than in SR/Jr rats. In fact, during the first 8 h after giving sodium orally the renal excretion of sodium was on an average eight times larger in the SR/Jr than in the SS/Jr rats. Renal excretion of sodium was similar in the two strains after intravenous administration. We conclude that the hypertensive SS/Jr rats have great difficulties in excreting an oral sodium load, a phenomenon that may be of importance in the pathophysiology of arterial hypertension in this strain of rats.     

The effects of enalapril on the natriuretic response evoked by an oral sodium load in sodium deprived normotensive and hypertensive rats

Previous studies have shown that an oral sodium load during sodium deprivation is excreted faster than an intravenous load. We wanted to study whether the renin-angiotensin-aldosterone system might be associated with this phenomenon and therefore the influence of the angiotensin converting enzyme (ACE) inhibitor enalapril was investigated. The experiments were performed on four strains of rat: spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats, inbred hypertension-prone (SS/Jr) and hypertension-resistant (SR/Jr) Dahl rats. In SHR and WKY rats pretreated with enalapril it was observed that an intravenous sodium load induced a renal sodium excretion which was between two and five times larger than that seen after an oral load. In SR/Jr and SS/Jr rats the sodium excretion was the same regardless of the route of administration. In SS/Jr rats sodium excretion increased three- to fourfold upon sodium repletion, whereas no significant increase was observed in SR/Jr rats. Thus, the present results indicate that an intact renin-angiotensin system is necessary for the interplay between the gastrointestinal tract and kidney.     

Lithium evokes a more pronounced natriuresis when administered orally than when given intravenously to salt-depleted rats

The effects on renal sodium excretion of giving lithium chloride (LiCl; 0.75 mmol per kg body mass) by gavage or intravenously were investigated. The experiments were carried out on Wistar-Kyoto (WKY) or spontaneously hypertensive (SHR) rats in metabolic cages. The rats had been on a low-salt diet for 4 days. Urine excretion of water, sodium and potassium was followed before and for 24 h after giving LiCl. An oral dose of LiCl evoked a more pronounced renal sodium excretion in either strain of rat as compared to that following intravenous administration, in agreement with previous observations of the effects of giving sodium chloride. Choline chloride (1.5 mmol per kg body mass) given by gavage to WKY rats or SHR evoked no change in the renal excretion of sodium. Based on the results of the present study and on observations reported in the literature, we propose that the intestinal tract contains a sodium ”sensor”, which upon activation releases a natriuretic factor to cause renal sodium excretion. The present results indicate that the proposed ”sensor” is sensitive to lithium but not chloride ions. Received: 24 June 1998 / Received after revision: 15 November 1998 / Accepted: 28 January 1999     

Renal function and sympathetic activity during mental stress in normotensive and spontaneously hypertensive rats

The aim of the present study was to explore the role of the renal sympathetic nerves in the urinary sodium excretion response to ‘mental stress’ in spontaneously hypertensive rats (SHR). In conscious male SHR and male Wistar Kyoto rats (WKY) urinary sodium excretion and renal function were measured both during ‘rest’ and during a 20 min period of ‘mental stress’. Experiments were also performed on renal denervated rats. In addition, renal sympathetic activity was measured in a separate group of rats. Urinary sodium excretion, similar at rest in SHR and WKY, decreased significantly more during the stress period in SHR (-64±5%) than in WKY (-34±7%), despite a greater arterial pressure increase in SHR. Renal sympathetic nerve activity which already at rest was higher in SHR than in WKY, also increased much more in SHR during stress than in WKY. The more intense renal sympathetic activation during stress may explain the greater reduction in urinary sodium excretion in SHR, because renal denervation almost abolished this latter response. Thus, during ‘mental stress’ the increased renal sympathetic activity reduces urinary sodium excretion in SHR despite the pressure rise, perhaps explaining why renal denervation delays the rise in arterial pressure in young SHR. The tachycardia response in SHR gradually subsided towards the end of the stress period, while renal sympathetic activity remained elevated. This indicates that neurogenic heart rate increases if anything underestimate the extent of sympathetic activation to e. g. the renal and splanchnic regions during increased alertness.     

Renal tubular reabsorption in spontaneously hypertensive rats.

We characterized renal tubular reabsorption before and during acute expansion in anesthetized 12-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Although mean arterial pressure was higher in euvolemic, nondiuretic SHR than in WKY, 158 vs. 114 mmHg, kidney and nephron glomerular filtration rate (GFR) as well as fluid reabsorption by the proximal convoluted tubule, loop of Henle, and distal convoluted tubule-collecting duct were similar. In euvolemic SHR with aortic constriction (SHR-AC), an acute decrease in renal perfusion pressure to 114 mmHg reduced sodium and water excretion. Kidney and nephron GFR and fluid reabsorption by segments along the nephron resembled values for SHR and WKY. Infusion of isotonic saline (3 ml.100 g body wt-1.h-1) produced similar increases in fractional sodium and water excretion by SHR and WKY, whereas SHR-AC exhibited a blunted natriuresis and diuresis. During expansion, fluid reabsorption by the nephron segments did not differ appreciably among the three groups. The effect(s) of perfusion pressure on reabsorption by superficial nephrons may be covert and was not unmasked, or may be manifested preferentially by deeper nephrons. We conclude that kidneys of SHR require a higher arterial pressure than kidneys of WKY to excrete a given amount of salt and water.     

Sensitivity of pressor responses to central hypertonic saline is greatly enhanced even in pre-hypertensive spontaneously hypertensive rats

It has been suggested that intracerebroventricular injection of hypertonic saline mimics the effects of a high salt diet in spontaneously hypertensive rats (SHR), a genetic model of hypertension. Intracerebroventricular injection of hypertonic saline produces an increase in blood pressure and the pressor response to hypertonic saline is enhanced in adult hypertensive SHR. In this study, we examined whether the intracerebroventricular hypertonic saline-induced pressor response is enhanced even in pre-hypertensive SHR. The basal mean blood pressure was almost the same in 4-week-old SHR and age-matched Wistar Kyoto rats (WKY), whereas it was greater in 15-16-week-old SHR than in age-matched WKY. Intracerebroventricular injection of hypertonic saline (10 microl of 230 mM NaCl) produced an increase in blood pressure in both 4-week-old and 15-16-week-old SHR, whereas it did not affect blood pressure in both age-matched WKY. Intracerebroventricular injection of hypertonic saline (10 microl of 260 mM NaCl) produced an increase in blood pressure in all rats but the pressor response was greater in both 4-week-old and 15-16-week-old SHR than in respective age-matched WKY. Intracerebroventricular injection of Phe-Met-Arg-Phe amide (FMRF), an FMRF-inducible sodium channel activator, produced an increase in blood pressure in all rats but the pressor response was greater in SHR than in WKY at both ages. These findings indicate that the sensitivities of pressor responses to intracerebroventricular hypertonic saline and FMRF are enhanced not only in hypertensive but also in pre-hypertensive SHR.     

Isotonic and hypertonic sodium loading in supine humans

The hypothesis that hypertonic saline infusion induces a greater natriuresis than infusion of the same amount of sodium as isotonic saline was tested in 8 supine subjects on fixed sodium intake of 150 mmol NaCl day^–1. Sodium loads equivalent to the amount of sodium contained in 10% of measured extracellular volume were administered intravenously over 90 min either as isotonic saline or as hypertonic saline (850 mmol L^–1). A third series without saline infusion served as time control. Experiments lasted 8 h. Water balance and sodium loads were maintained by replacing the excreted amounts every hour. Plasma sodium concentrations only increased following hypertonic saline infusion (by 2.7 ± 0.3 mmol L^–1). Oncotic pressure decreased significantly more with isotonic saline (4.1 ± 0.3 mmHg) than with hypertonic saline (3.2 ± 0.2 mmHg), indicating that isotonic saline induced a stronger volumetric stimulus. Renal sodium excretion increased more than a factor of four with isotonic and hypertonic saline but also increased during time control (factor of three). Cumulated sodium excretions following isotonic (131 ± 13 mmol) and hypertonic saline (123 ± 10 mmol) were statistically identical exceeding that of time control (81 ± 9 mmol). Plasma angiotensin II decreased in all series but plasma ANP concentrations and urinary excretion rates of endothelin-1 remained unchanged. In conclusion, hypertonic saline did not produce excess natriuresis. However, as the two loading procedures induced similar natriureses during different volumetric stimuli, part of the natriuresis elicited by hypertonic saline could be mediated by stimulation of osmoreceptors involved in renal sodium excretion. The supine position does not provide stable time control conditions with regard to renal excretory function.     

Stimulation of renal sodium excretion in mature rats

In adult rats a saline load is followed by an increase in renal excretion of sodium and by a low rate of ion exchange (hydrogen ions and potassium for sodium), caused by inhibited aldosterone secretion. Under analogous conditions a saline load provoked sodium retention and a distinct increase in renal excretion of hydrogen ions and potassium in young rats, which can be explained by a non-regulated, very intensive ion exchange. The repeated administration of NaC1 solution alone and in combination with cyclopenthiazide produced an accelerated maturation of kidney function in 10- and 33day-old rats measurable by an increase in sodium excretion and reduced ion exchange. In adult rats as well as immediately after birth (5-day-old rats) this effect cannot be provoked by the various pretreatments acting in mature rats.     

Sodium balance during development of hypertension in the spontaneously hypertensive rat (SHR)

Sodium balance was studied in 7 and 16 week old male spontaneously hypertensive rats (SHR), in matched normotensive Wistar rats (NCR) and in Wistar Kyoto rats (WKR). The animals were placed in metabolic cages and given diets with either normal sodium content (5.35 mmol sodium/100 g food) or with a sodium content 3 or 10 times the normal. Whether on normal or increased sodium diet we did not observe any increased sodium retention in either SHR age group. However, in both SHR groups urinary sodium excretion was significantly decreased, while faecal sodium excretion was correspondingly increased compared with the controls. This shift of sodium excretion from kidneys to gastrointestinal tract in SHR did not reflect any ‘primary’ inability of the SHR kidneys to excrete sufficient sodium amounts since on high sodium diet they excreted the increased sodium load as readily as the normotensive controls. The present results do not support the concept that a primary renal retention of sodium and water should be of pathogenetic importance for the SHR variant of primary hypertension.     

Sodium handling by the Sabra hypertension prone (SBH) and resistant (SBN) rats

The acute and chronic renal handling of salt was evaluated in age matched Sabra hypertension-prone (SBH) and hypertension-resistant (SBN) rats. Acute oral (4 ml/100 g) and intravenous (3.3 ml/100 g) isotonic saline loading in unanesthetized normotensive animals maintained on normal diet elicited a significantly lesser diuretic and natriuretic response in SBH than in SBN. Intermittent studies in metabolic cages in rats aged 5 to 21 weeks showed that both strains consumed similar amounts of salt but that SBH excreted significantly less urinary sodium than SBN (F=40,p<0.001). Twenty four hour clearance studies showed a similar filtered sodium load in the two strains but a lower total and fractional sodium excretion in SBH, suggesting increased tubular reabsorption. Under conditions of water diuresis, free water clearance was similar in the two strains, suggesting the site for disparate tubular sodium handling to be distal to the thick medullary ascending limb of the loop of Henle. Acute oral saline loading and long term studies in metabolic cages in rats prepared with deoxycorticosteroneacetate (doca) and salt showed no significant differences in sodium excretion between hypertensive SBH and normotensive SBN. These findings indicate disparate renal sodium handling between SBH and SBN rats, already apparent before the onset of hypertension, which dissipates during doca-salt treatment.     

Age-related changes in the renal dopaminergic system and expression of renal amino acid transporters in WKY and SHR rats

This study examined age-related changes in renal dopaminergic activity and expression of amino acid transporters potentially involved in renal tubular uptake of l-DOPA in Wistar Kyoto (WKY) and spontaneously hypertensive rats. Aging (from 13 to 91 weeks) was accompanied by increases in systolic blood pressure (SBP) in both WKY and SHR. The sum of urinary dopamine and DOPAC and the urinary dopamine/l-DOPA ratio were increased in aged SHR but not in aged WKY. The urinary dopamine/renal delivery of l-DOPA ratio was increased in both rat strains with aging. LAT2 abundance was increased in aged WKY and SHR. The expression of 4F2hc was markedly elevated in aged SHR but not in aged WKY. ASCT2 was upregulated in both aged WKY and SHR. Plasma aldosterone levels and urinary noradrenaline levels were increased in aged WKY and SHR though levels of both entities were more elevated in aged SHR. Activation of the renal dopaminergic system is more pronounced in aged SHR than in aged WKY and is associated with an upregulation of renal cortical ASCT2 in WKY and of LAT2/4F2hc and ASCT2 in SHR. This activation may be the consequence of a counter-regulatory mechanism for stimuli leading to sodium reabsorption.     

Renal nerve activity and exaggerated natriuresis in conscious spontaneously hypertensive rats

Exaggerated natriuresis upon volume loading occurs in both human and animal hypertension and is mainly due to suppressed tubular reabsorption. To explore whether altered renal sympathetic activity contributes to this response, conscious male spontaneously hypertensive rats (SHR) were exposed to isotonic saline loading in comparison with normotensive male Wistar Kyoto rats (WKR). After a 60 min control hydropenic period, during which mean arterial pressure, heart rate, renal sympathetic nerve activity and urinary sodium excretion were followed, a 60 min period of intravenous volume expansion with isotonic saline (0.2 ml/minx 100 g b. w.) was started followed by a 60 min hydropenic recovery period. Already during the control period sodium excretion was significantly higher in SHR. During the volume load and subsequent recovery period a clearly exaggerated natriuresis occurred in SHR compared with WKR. Further, volume loading reduced renal sympathetic nerve activity in all animals, but significantly more in SHR. Moreover, volume loading reduced mean arterial pressure and heart rate in both groups. It is suggested that the accentuated reflex inhibition of renal sympathetic activity in SHR upon volume loading emanates from cardiac mechanoreceptors and partly explains the exaggerated natriuresis in SHR. This augmented ‘volume’ reflex response is probably due to reduced systemic venous compliance in SHR with a consequently increased central filling and cardiac receptor activation.     

Blood pressure and heart rate responses to mental stress in spontaneously hypertensive (SHR) and normotensive (WKY) rats on various sodium diets

Normotensive (WKY) and hypertensive rats (SHR) were, from 5 to 12 weeks of age, given ‘low’ (LNa), ‘control’ and ‘high’ (HNa) Na diets (0.5, 5 and 50 mmol-100 g^-1 food, respectively, during weekly recordings of body weight, conscious indirect systolic blood pressure (SBP) and heart rate (HR). During the last week, mean arterial pressure (MAP) and HR responses to standardized stress stimuli (air jet) were recorded before and after sequential cardiac nerve blockade. While resting, SBP was about equal in all WKY groups, but it was significantly reduced in SHR-LNa (152 mmHg versus 174 and 178 mmHg in SHR controls and HNa; P < 0.05). In both LNa groups HR was elevated nearly 25% compared with controls, being in SHR 513 versus 419 bpm (P < 0.01) and in WKY 489 versus 393 bpm (P < 0.01). Cardiac nerve blockade indicated that this HR elevation was about equally due to elevations of sympathetic activity and ‘intrinsic’ pacemaker activity. SHR-LNa also showed attenuated MAP elevations to acute mental stress. There were, however, no significant differences between groups concerning haematocrit or plasma Na-K levels. The results suggest that SHR have a greater salt requirement than WKY, as Na restriction to one-tenth of normal led to a considerable MAP reduction in SHR despite compensatory sympathetic activation, and also to attenuated pressor responses to mental stress. Further, the cardiovascular effects in SHR were much more extensive when on a low-Na diet than when Na intake was increased tenfold above normal.     

Cisplatin-induced nephrotoxicity causes altered renal hemodynamics in Wistar Kyoto and spontaneously hypertensive rats: Role of augmented renal alpha-adrenergic responsiveness

The pathogenesis of cisplatin-induced renal failure is related to reduced renal blood flow due to severe tubular damage and enhanced renovascular resistance. It is also known that alpha(1)-adrenoceptors, the major subtype of alpha-adrenoceptors in renal vasculature play the pivotal role in regulating renal hemodynamics. With this background, we have hypothesized that the altered renal hemodynamics and enhanced renovascular resistance in cisplatin-induced renal failure might be caused by the altered alpha-adrenergic responsiveness with a possible involvement of alpha(1)-adrenoceptors in the renal vasculature. In a unique experimental approach with anesthetized rats, this study has therefore examined if there is any shift in the renovascular responsiveness to renal nerve stimulation and a series of alpha-adrenergic agonists in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats with cisplatin-induced renal failure in comparison with their body weight-matched normal controls. Thirty-two male rats of both WKY (n=16) and SHR (n=16) origin with body weight 236+/-7.9 g received cisplatin (5mg/kg i.p.). The renal failure was confirmed in terms of significantly reduced renal blood flow, reduced creatinine clearance, increased fractional excretion of sodium, increased kidney index (all P<0.05) and tubular damage. After 7 days of cisplatin, the overnight fasted rats were anesthetized (sodium pentobarbitone, 60 mg/kg i.p.) and renal vasoconstrictor experiments were done. The changes in the vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by electrical renal nerve stimulation or intrarenal administration of noradrenaline, phenylephrine and methoxamine. It was observed that in the cisplatin-treated renal failure WKY and SHR rats there were significant (all P<0.05) reductions in the renal blood flow along with significantly (P<0.05) higher renal adrenergic responsiveness as compared with their non-renal failure controls. The data showed that in the renal failure WKY and SHR rats, the altered renal hemodynamics might be caused by an augmented renal adrenergic responsiveness. The results obtained further led us to suggest that the augmented renal adrenergic responsiveness in the cisplatin-induced renal failure rats were possibly mediated by the alpha(1)-adrenoceptors.     

Low sodium intake induces an increase in renal monoamine oxidase activity in the rat. Involvement of an angiotensin II dependent mechanism

AIMS: The interplay between natriuretic dopamine and antinatriuretic angiotensin II represents an important mechanism for the regulation of renal sodium and water excretion. Monoamine oxidase is the main metabolizing pathway for dopamine in the renal cortex. In this study, we have analysed the effect of low sodium feeding and AT1 receptor blockade on renal dopamine metabolism by monoamine oxidase. METHODS: Four groups of rats were studied: 1, normal salt diet (NS); 2, low salt diet (LS); 3, NS receiving Losartan (Los, specific AT1 receptor antagonist, 20 mg kg(-1) bwt day(-1), NS + Los); 4, LS receiving Los (LS + Los). RESULTS: Urinary dopamine excretion was lower in LS than in NS rats (543 +/- 32 vs. 680 +/- 34 ng day(-1) 100 g(-1) bwt, P < 0.05). When treated with Los, DOPAC excretion and urinary DOPAC/dopamine ratio fell significantly in the LS + Los group as compared with the LS group (1199 +/- 328 vs. 3081 +/- 681 ng day(-1) 100 g(-1) bwt and 1.90 +/- 0.5 vs. 5.7 +/- 1.2, respectively, both P < 0.02). Losartan increased hydroelectrolyte excretion in the LS group. No changes were found in the NS + Los group. Aromatic L-amino acid decarboxylase activity in cortex was similar in NS and LS rats. Instead, monoamine oxidase activity was higher in cortical homogenates from LS rats (in nmol mg tissue(-1) h(-1): NS 7.66 +/- 0.52; LS 9.82 +/- 0.59, P < 0.05) and this difference was abolished in LS + Los rats (7.34 +/- 0.49 nmol mg tissue(-1) h(-1), P < 0.01, vs. LS). CONCLUSIONS: We have concluded that low levels of dopamine in the urine of LS rats are because of an increase in the activity of renal monoamine oxidase and that angiotensin II mediates this increase through stimulation of AT1 receptors.     

Renal and cardiovascular effects of atrial natriuretic peptide in Wistar-Kyoto and spontaneously hypertensive rats during a chronic salt loading

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were maintained on tap water or 1.5% NaCl for 3 weeks. During the high sodium regime 24-h urinary sodium excretion increased 10-fold and the basal blood pressure increased in the SHR. After 3 weeks the rats received arterial (carotid artery), venous and bladder catheters (suprapubic). Saline was infused continuously and in conscious rats atrial natriuretic peptide (alpha-hANP) was administered as bolus injections (8 and 16 nmol kg-1) and the blood pressure and heart rate and the urinary excretions of sodium, potassium (flame photometry), noradrenaline and dopamine (HPLC) were followed at 5-min intervals. The administration of ANP caused a short-lasting blood pressure reduction, tachycardia, diuresis and increased urinary excretions of sodium, potassium, noradrenaline and dopamine. The blood pressure responses to ANP did not differ between the rat strains, irrespective of the diet. The natriuresis and diuresis to ANP was reduced in animals on a high sodium diet, especially in the SHR. This may be interpreted as a down-regulation of target organ responsiveness to ANP during a high sodium diet and the inappropriately large decrease in the responsiveness that was observed in the SHR may be related to increase in blood pressure during the high sodium diet.     

血管紧张素Ⅱ受体拮抗剂对高血压肾小动脉重建的影响

目的:研究血管紧张素II(AngII)受体拮抗剂对高血压肾小动脉重建的影响。方法:18只4周龄雄性大鼠分为:正常血压大鼠(WKY)组、自发性高血压大鼠(SHR)组、SHR口服losartan组,均饲养至16周。在肾组织切片上分别用光镜和电镜配合计算机图像分析法观测肾组织内小动脉的几何形态学指标和小动脉平滑肌及其间隙,离体肾脏灌流法测定最小肾血管阻力。结果:Losartan组的尾动脉收缩压、肾小动脉壁厚、壁面积、壁厚内径比和中层血管平滑肌细胞宽度以及最小肾血管阻力,均显著低于高血压对照组。结论:AngII受体拮抗剂losartan能预防SHR肾小动脉的重建。     

不同剂量罗沙坦对高血压大鼠冠状动脉壁肥厚的逆转作用

为研究罗沙坦对高血压冠状动脉壁肥厚的逆转作用。将１６周大鼠分为自发性高血压大鼠（ＳＨＲ）组、ＳＨＲ口服大剂量罗沙坦组「１５ｍｇ／（ｋｇ／ｄ）」、ＳＨＲ口服小剂量罗沙坦组「０．７５ｍｇ／（ｋｇ．ｄ）」和正常血压大鼠（ＷＫＹ）组,饲养１０周,结果显示大剂量罗沙坦治疗显著降低ＳＨＲ的收缩压,降低冠状动脉壁横截面积、横截面积与内径比,提高最大冠状动脉流量小剂量罗沙坦治疗对ＳＨＲ的收缩压,外径〉２００ｕｍ冠