NATRIURETIC EFFECT OF CHRONICALLY ADMINISTERED α-HUMAN ATRIAL NATRIURETIC POLYPEPTIDE IN SODIUM DEPLETED OR REPLETED CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS

Hypotensive and natriuretic effects of chronically administered alpha-human atrial natriuretic polypeptide (alpha-hANP) were investigated in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) in both sodium depletion and repletion. Systolic blood pressure was significantly reduced in SHR and WKY in both sodium deplete and replete states. Urinary sodium excretion was significantly increased in SHR and tended to be increased in WKY on sodium repletion, but remained unchanged on sodium depletion. It is suggested that extracellular fluid volume may be an important determinant factor of the natriuretic action of ANP but may not affect the hypotensive effect.     

Effect of clonidine on renal sodium handling in spontaneously hypertensive rats

Up-regulation of kidney α2-adrenoceptor expression has been implicated in the development of hypertension in spontaneously hypertensive rats (SHR). This study was carried out to evaluate renal sodium excretion in response to clonidine administration in SHR and control normotensive Wistar-Kyoto (WKY) rats. SHR and WKY rats (12-week-old) were placed in metabolic cages for 4 days: the first 2 days in control conditions and the following 2 days under oral clonidine treatment (100 μg/kg body weight). Clonidine produced a similar reduction in systolic blood pressure values in SHR and WKY rats, although SHR remained hypertensive. At the end of the study SHR and WKY rats presented similar noradrenaline plasma levels. However, noradrenaline kidney tissue levels were significantly higher in SHR compared to WKY rats. Under control conditions, SHR presented lower urine flow compared to WKY rats. Clonidine produced a significant decrease in urine flow in WKY rats but not in SHR. Furthermore, clonidine also produced a significant reduction in urinary sodium, potassium, and creatinine excretion in WKY rats, but had no effect in SHR. In conclusion, in SHR the reduction in systolic blood pressure and sympathetic activity produced by clonidine was not accompanied by a decrease in urine volume and sodium excretion.     

HYPOTENSIVE EFFECT OF CHRONICALLY INFUSED ADRENOMEDULLIN IN CONSCIOUS WISTAR-KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS

1. The hypotensive effect of chronically infused human adrenomedullin (hAM), a potent vasodilator peptide that has been reported to have a natriuretic action, was examined in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Conscious WKY rats and SHR were infused with 200 ng/h synthetic hAM for 14 days by means of osmotic minipumps. Control groups were infused at the same schedule with 0.9% saline. Systolic blood pressure (SBP) and daily urinary excretion of Na⁺ and K⁺ were measured before and during the infusion period. In addition, plasma renin activity (PRA), aldosterone and hAM concentrations were measured on day 14 of infusion. 3. A significant reduction in SBP was observed in hAM-treated SHR at day 2 and SBP remained significantly lower throughout the experiment compared with control SHR. Similarly, SBP in the hAM-treated WKY rats was found to be significantly lower than in control WKY rats during infusion. However, the hypotensive effect was not accompanied by any significant increase in urinary volume or Na⁺ excretion in hAM-treated rats of either strain. Chronic infusion with hAM significantly suppressed PRA and lowered the concentration of plasma aldosterone in WKY rats but not in SHR. The plasma hAM levels in treated WKY rats and SHR were 0.0 ± 9.4 and 0.6 ± 0.2 fmol/mL, respectively. 4. These findings demonstrate that chronically infused hAM has a hypotensive effect in both WKY rats and SHR without an increase in urinary volume or Na⁺ excretion at a plasma AM concentration within the physiological limit.     

EFFECTS OF PROLONGED (48 H) INFUSION OF CORTISOL ON BLOOD PRESSURE, RENAL FUNCTION AND FETAL FLUIDS IN THE IMMATURE OVINE FOETUS

1. This study describes the effects of prolonged (48 h) infusion of cortisol into ovine foetuses (100–110 days of gestation: term is 150 days) at a time when endogenous plasma cortisol concentrations are <5 nmol/L. 2. In four chronically cannulated foetuses (107 ± 0.9 day) the infusion of saline (0.9% NaCl; w: v 0.19 mL/h, 48 h) had no effect on blood pressure, renal function, or composition of amniotic and allantoic fluids. 3. In six foetuses (107 ± 1 day) the infusion of cortisol (250 μg/h) increased plasma cortisol concentrations from 4.1 ± 0.7 to 118 ± 9 nmol/L (P < 0.001), increased mean arterial pressure from 34 ± 1 to 40 ± 1 mmHg (P < 0.001), increased glomerular filtration rate (P<0.05), urine flow rate, and free water clearance (P<0.01). 4. There was a significant increase in excretion rates of potassium and creatinine as a result of cortisol infusion, but no natriuresis, indicating some functional maturation of the fetal kidney. 5. Cortisol infusion had no effect on the volumes of amniotic and allantoic fluids; allantoic fluid composition was unchanged; significant decreases occurred in amniotic fluid osmolality, sodium and chloride concentrations, and in lung liquid osmolality, potassium, creatinine, magnesium, glucose and fructose concentrations. 6. Thus prolonged exposure of the immature ovine foetus to elevated cortisol concentrations produced significant alterations in the water and electrolyte balance of the foetus.     

DIFFERENTIAL REGULATION OF UTERINE AND GLOMERULAR ANGIOTENSIN II RECEPTORS IN NORMAL AND HYPERTENSIVE PREGNANCY IN THE RAT

1. In the non-pregnant state uterine and glomerular angiotensin II (AII) receptors have been shown to regulate in a similar fashion. This study sought to determine whether such parallel regulation occurred during pregnancy. We also investigated the role of plasma AII in these changes. 2. These studies were performed in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). The SHR has increased receptor number, increased sensitivity to infused AII and decreased plasma volume compared to the WKY. These features are also seen in pregnancy induced hypertension (PIH). 3. Age matched female WKY and SHR were exposed to an appropriate breeder and sacrificed on day 14 of gestation. Plasma AII was measured by radio-immunoassay. Uterine and glomerular receptor binding was determined by saturation analysis using ¹²⁵I(Sar¹,Ileu⁸)AII. Data were analysed using the program ligand. 4. Uterine and glomerular AII receptors showed different patterns of regulation during pregnancy. The uterine AII receptor affinity decreased significantly in both strains at 14 days of gestation and receptor number also decreased significantly in WKY. In contrast, glomerular AII receptor affinity did not change significantly in either strain. Receptor numbers in the glomeruli increased significantly compared to their respective non-pregnant controls. 5. We conclude that the uterine and glomerular AII receptors do not regulate in a parallel fashion in pregnancy. Plasma AII concentration does not appear to be involved in the regulation of either uterine and glomerular receptor expression in pregnancy.     

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 NEONATAL SYMPATHECTOMY BY 6-HYDROXYDOPAMINE ON BLOOD PRESSURE AND INTRAVASCULAR VOLUME IN YOUNG STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

1. Stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY) were 'chemically sympathectomized' immediately after birth with 6-hydroxydopamine (6-OHDA, 100 mg/kg s.c. daily) for the first 10 days of life. 2. Body weight gain was diminished in both groups as compared with sham-treated controls. Blood pressure was reduced in 'sympathectomized' SHRSP, and also WKY rats had a slightly lower blood pressure than control rats. 3. Plasma concentration of angiotensin II and renin content of the kidney were not influenced by 6-OHDA. 4. 'Sympathectomized' SHRSP retained similar amounts of sodium than sham-treated SHRSP when sodium retention is expressed per body weight gained. Plasma and blood volumes were increased in both SHRSP and WKY rats, whereas packed cell volume was significantly decreased. 5. These results demonstrate the significance of an intact sympathetic nervous system for the development of hypertension in SHRSP. The expanded plasma and blood volume in 'sympathectomized' rats indicate an important role of the sympathetic nervous system and/or the arterial blood pressure for the regulation of intravascular volume.     

POTENTIATION OF DIPSOGENIC ACTIONS BY CENTRALLY ADMINISTERED TYPE-C NATRIURETIC PEPTIDE IN SPONTANEOUSLY HYPERTENSIVE BUT NOT WISTAR-KYOTO RATS

1. The effects of type-C natriuretic polypeptides (CNP) on the central dipsogenic and pressor responses to angiotensin II (AngII) were studied by the administration of agents into the lateral cerebral ventricle under conscious and unrestrained conditions in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. The fluid intake induced by AngII (25 ng) and water deprivation were potentiated after pretreatment with CNP in SHR but not in WKY rats. However, carbachol-induced water intake was not altered by pretreatment with CNP (2.5 μg) in either WKY rats or SHR. 3. In contrast, CNP did not influence the pressor responses to AngII in either WKY rats o. SHR.     

DIFFERENCES IN THE DENSITY OF BAROSENSITIVE NEURONS IN THE MEDULLA OF SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS

1. The density of barosensitive neurons in the medulla was examined in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto (WKY) rats. In control experiments, rats were sham-operated, while in test experiments arterial baroreceptors were stimulated by pressor responses to i.v. administration of phenylephrine and the density of c-Fos-labelled neurons was immunocytologically examined. 2. In both control and test experiments, c-Fos-labelled neurons were distributed in cardiovascular control sites: the nucleus trac-tus solitarii (NTS) and the caudal and rostral ventrolateral medullas (CVLM/RVLM). 3. In both WKY rats and in SHR, the total density of labelled neurons in test experiments was significantly higher than in control experiments. 4. In control experiments, no significant difference was found in the distribution and density of labelled neurons in the NTS and in the CVLM/RVLM between WKY rats and SHR. 5. In test experiments, no significant difference was found in the distribution and density of labelled neurons in the NTS between WKY rats and SHR. 6. In test experiments in SHR, the density of labelled neurons in the CVLM just caudal to the obex level was significantly higher than that in WKY rats, whereas the density of labelled neurons in WKY rats in the RVLM just rostral to the obex level was significantly higher than that in SHR. 7. These results indicate that stimulation of the arterial baro-receptor induces strain-specific differences in the density of barosensitive neurons in the CVLM/RVLM near the obex level.     

EFFECT OF CROSS-FOSTERING ON NEONATAL SODIUM BALANCE AND ADULT BLOOD PRESSURE IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. The aim of the present study was to compare electrolyte handling in naturally reared neonatal spontaneously hypertensive rats (SHR) with those reared by a Wistar-Kyoto (WKY) rat foster mother (denoted SHRX), as cross-fostering SHR pups to a WKY rat dam lowers adult blood pressure in the SHR. 2. The electrolyte content of WKY rat and SHR dams’ milk was determined and electrolyte intake and urinary excretion rates were calculated in both naturally reared and cross-fostered WKY rat and SHR pups. 3. The milk sodium concentration fell in both strains (WKY rat: 31.8 ± 2.0 to 15.2 ± 1.2 mmol/L; SHR 31.9 ± 2.5 to 18.2 ± 1.6 mmol/L; P < 0.001), as did potassium (P < 0.001), over lactation, but there were no differences between strains. Calcium and magnesium concentrations increased (P< 0.001), although SHR dam's milk contained less calcium (P < 0.001) than that of WKY rat dams during the third week of lactation. 4. Spontaneously hypertensive rat pups ingested less milk (P<0.05) than WKY rat pups; therefore, their cumulative sodium intake over postnatal days 4–15 was significantly lower than that of WKY rat pups (WKY rat vs SHR: 84.4 ± 3.6 vs 59.7 ± 2.6 μmol/g bodyweight, respectively; P < 0.05) and fostered SHRX pups (77.7 ± 7.0 μmol/g bodyweight; P < 0.05). Potassium and magnesium intakes were comparable between SHR, WKY rat and SHRX pups, but SHR pups ingested significantly less calcium than either WKY rat pups (136.1 ± 6.4 vs 200.1 ± 9.5p, mol/g bodyweight, respectively; P<0.05) or SHRX pups (200.0 ± 18.0 μmol/g bodyweight; P<0.05). 5. These data show that the neonatal SHR experiences a period of sodium deficiency during the developmental stage when cross-fostering is effective in lowering blood pressure. This is consistent with the reported up-regulation of the renin-angiotensin system observed in SHR at this time and may have a long-term influence on blood pressure.     

The effect of medetomidine, an alpha 2-adrenoceptor agonist, on plasma atrial natriuretic peptide levels, haemodynamics and renal excretory function in spontaneously hypertensive and Wistar-Kyoto rats.

1. The effects of the selective alpha 2-adrenoceptor agonist, medetomidine, were assessed on plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP), haemodynamics and on urine water and solute excretion in conscious, chronically cannulated, 7 month-old spontaneously hypertensive (SHR) and age-matched Wistar-Kyoto (WKY) rats, in order to examine the role of alpha 2-adrenoceptors in the control of ANP secretion. 2. A 60 min i.v. infusion of medetomidine (0.2 or 0.6 microgram kg-1 min-1) decreased heart rate dose-dependently in both strains. Medetomidine infusion (0.6 microgram kg-1 min-1) resulted in an increase in mean arterial pressure in WKY, whereas both doses decreased blood pressure in SHR. There was a slight increase in the right atrial pressure in both strains (WKY: +1.18 +/- 0.26 mmHg; SHR: +1.64 +/- 0.64 mmHg, NS) in response to infusion of 0.6 microgram kg-1 min-1 of medetomidine. 3. No differences were found in resting plasma IR-ANP levels between WKY (114 +/- 8 pg ml-1, n = 19) and SHR (117 +/- 10 pg ml-1, n = 21). Infusion of equibradycardic doses of medetomidine increased dose-dependently plasma IR-ANP levels in WKY, but did not affect the plasma IR-ANP concentration in SHR rats. 4. Despite the different effect of medetomidine on ANP release in WKY and SHR rats, i.v. administration of medetomidine affected renal excretory functions similarly in both strains; urine flow and sodium excretion increased and urine osmolality decreased significantly, while there was no consistent change in urinary potassium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

HYPOTENSIVE ACTIVITY OF AQUEOUS EXTRACT OF ANDROGRAPHIS PANICULATA IN RATS

1. The hypotensive activity of an aqueous extract of Andrographis paniculata was studied using chronic intraperitoneal (i.p) infusions by osmotic pumps. The extract exhibited a dose-dependent hypotensive effect on the systolic blood presure (SBP) of spontaneously hypertensive rats (SHR). 2. The optimum hypotensive dose determined was repeated in a study in SHR and their normotensive controls, Wistar Kyoto (WKY) rats, to demonstrate its comparative effects on the SBP, plasma and lung angiotensin-converting enzyme (ACE) activities, as well as on lipid peroxidation in the kidneys, as measured by thiobarbituric acid (TBA) assay. 3. The extract significantly lowered the SBP of both SHR and WKY rats. 4. Plasma, but not lung, ACE activity and kidney TBA level were significantly lower in extract-treated SHR when compared with vehicle-treated SHR controls. 5. Plasma and lung ACE activities as well as kidney TBA levels were not significantly different between extract-and vehicle-treated WKY rats. 6. This study indicates that the aqueous extract of A. paniculata lowers SBP in the SHR possibly by reducing circulating ACE in the plasma as well as by reducing free radical levels in the kidneys. The mechanism(s) of hypotensive action seems to be different in WKY rats.     

NEUROVASCULAR FUNCTION DURING PREGNANCY IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. Blood pressure (BP) declines dramatically in the final week of gestation in the pregnant spontaneously hypertensive rat (SHR). This study investigated the hypothesis that alterations of vascular neuroeffector function in the pregnant SHR and normotensive Wistar-Kyoto (WKY) rat are responsible for this decline. 2. Pregnancy in SHR and WKY rats was associated with a significant drop in BP in the last week of gestation. 3. Responses of the perfused mesenteric vasculature to bolus doses of noradrenaline (NA) and potassium chloride (KCl) were decreased in preparations from SHR rats 4 days before delivery. This decreased responsiveness was absent in preparations from SHR rats 1 day before delivery. Responses of the perfused mesenteric vasculature to sympathetic nerve stimulation were not influenced by pregnancy in the SHR. 4. It is concluded that while there are dynamic changes occurring in neurovascular function just prior to delivery, it is unlikely that they are wholly responsible for the dramatic decline in blood pressure in the SHR rat.     

Release of serotonin in the locus coeruleus of normotensive and spontaneously hypertensive rats (SHR)

The aim of the present work was to clarify whether differences exist between the release of endogenous serotonin in the locus coeruleus of normotensive and hypertensive rats. The locus coeruleus was superfused with artificial cerebrospinal fluid (aCSF) through a push-pull cannula and serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined in the superfusate by HPLC combined with electrochemical detection. Compared with normotensive Wistar-Kyoto (WKY) rats, the basal release rate of serotonin in the locus coeruleus of spontaneously hypertensive rats (SHR) was increased more than twofold. Intravenous infusion of noradrenaline (4 μg/kg min) increased mean arterial blood pressure to the same extent in hypertensive and normotensive rats. The pressor response was associated with an increased serotonin release. In WKY rats, the release of serotonin in the locus coeruleus evoked by noradrenaline infusion was more pronounced than in SHR. In WKY rats, intravenous infusion of sodium nitroprusside (150 μg/kg min) led to a fall in blood pressure which was less pronounced and lasted shorter than in SHR. The depressor response was associated with decreased serotonin release. In WKY rats, the decrease in serotonin release evoked by sodium nitroprusside was more pronounced and lasted longer than in SHR. Neither noradrenaline nor sodium nitroprusside influenced the outflow of 5-HIAA. The sensory stimuli noise and tail pinch led to a slight rise in arterial blood pressure which was similar in WKY rats and SHR. These stimuli enhanced the release rate of serotonin and the outflow of 5-HIAA to the same extent in the locus coeruleus of normotensive and hypertensive rats. The findings suggest that the enhanced release of serotonin in the locus coeruleus of genetically hypertensive rats reflects a mechanism counteracting the disturbed blood pressure homeostasis. Stressors influence blood pressure and release of serotonin in the locus coeruleus of SHR and WKY rats to the same extent. Received: 16 November 1998 / Accepted: 22 February 1999     

INVOLVEMENT OF HYPOTHALAMIC ADRENALINE IN THE CLONIDINE WITHDRAWAL SYNDROME IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

1. The concentrations of adrenaline and other catecholamines (noradrenaline and its major metabolite DHPG, dopamine and its major metabolite DOPAC) were measured in the hypothalamus and medulla oblongata of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) which had received a continuous subcutaneous infusion of clonidine (10 micrograms/kg per h) for 10 days, and also in WKY and SHR rats which were killed 15-18 h after the cessation of the 10-day infusion. 2. The concentrations of adrenaline in the hypothalamus and medulla oblongata/pons of the clonidine treated WKY and SHR rats were not different from their respective controls. However, the adrenaline concentrations in the hypothalamus (but not the medulla oblongata) were significantly decreased in the post-infusion WKY and SHR. 3. These results suggest that hypothalamic adrenergic mechanisms may have a common involvement in the post-clonidine infusion syndromes displayed by the WKY and SHR strains.     

COMPLEMENTARY CHANGES IN PLASMA ATRIAL NATRIURETIC PEPTIDE AND ANTIDIURETIC HORMONE CONCENTRATIONS IN RESPONSE TO VOLUME EXPANSION AND HAEMORRHAGE: STUDIES IN CONSCIOUS NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

1. Plasma concentrations of atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) were measured in conscious stroke-prone spontaneously hypertensive (SPR), spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats before and after acute volume expansion or haemorrhage. 2. Plasma ANP concentration was reduced to one-third of resting values 30 min after a 1.5% haemorrhage (1.5 ml of blood per 100 g bodyweight). Plasma ADH concentration rose immediately 50-fold on haemorrhage and remained elevated at 30 min. 3. Plasma ANP concentration increased 2.5-fold relative to resting values 1 min after infusion of 2.0 ml per 100 g 5% dextrose; after 10 min plasma ANP remained elevated. Plasma ADH concentration tended to fall on volume expansion although no significant decrease was observed. 4. There was no difference in the basal levels of ANP and ADH, or in the changes produced by alterations in blood volume, in hypertensive SPR and SHR compared with normotensive WKY. 5. Thus, plasma ANP concentrations moved in opposite directions in response to two physiological stimuli: volume expansion and haemorrhage. Reciprocal changes were observed in plasma ADH.     

Antihypertensive activity of the aqueous extract of Retama raetam Forssk. leaves in spontaneously hypertensive rats

The antihypertensive and diuretic effects of the aqueous extract of Retama raetam Forssk. (RR) leaves were studied in both normotensive (WKY) and spontaneously hypertensive rats (SHR). In SHR rats, daily oral administration of RR (20 mg/kg) for three weeks exhibited a significant reduction in blood pressure. The systolic blood pressure decreased significantly from the seventh day (P < 0.01) and persisted through the end of treatment (P < 0.001) in SHR rats. The RR significantly enhanced the diuresis in WKY rats (P < 0.001). Furthermore, oral administration of RR at a dose of 20 mg/kg produced a significant increase on urinary excretion of sodium (P < 0.05), potassium (P < 0.01) and chlorides (P < 0.01) in SHR rats. In WKY rats, RR treatment induced a significant increase on urinary potassium elimination (P < 0.05) without affecting sodium and chloride excretion. Irbesartan (Avapro) 20 mg/kg (body weight), an angiotensin II receptor antagonist, was used as reference drug. No significant changes were noted in heart rate after RR treatment in SHR as well as in WKY rats. Glomerular filtration rate showed a significant increase after RR administration in WKY rats (P < 0.01) and a no significant increase in SHR rats. These results suggest that oral administration of aqueous RR extract exhibited antihypertensive and diuretic effects in SHR rats and diuretic action in WKY rats.     

ENHANCED SENSITIVITY OF MEDULLARY DEPRESSOR NEURONS TO N-METHYL-D-ASPARTATE–GLYCINE SITE ANTAGONISTS IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. The effects of the specific N -methyl- D -aspartate (NMDA)–glycine site antagonist 5-fluoro indole-2-carboxylic acid (FICA) and NMDA, microinjected into the vasodepressor caudal ventrolateral medulla, were compared in spontaneously hypertensive rats (SHR) and in Wistar-Kyoto (WKY) rats.
2. 5-Fluoro indole-2-carboxylic acid elicited a significant pressor response (+20.0±4.9 mmHg) in SHR, but no change was found in the basal blood pressure of WKY rats.
3. The depressor response due to NMDA microinjection was significantly larger in SHR (–48.0±4 mmHg) than in WKY rats (–23.0±1.9 mmHg).
4. Pre-injection of FICA attenuated the depressor effects of NMDA significantly, this blockade being significantly more pronounced in SHR (37.0±2.7 mmHg) than in WKY rats (12.0± 1.2 mmHg).
5. The enhanced responses to FICA may reflect the lower levels of the endogenous NMDA–glycine antagonist kynurenic acid in SHR compared with WKY rats.     

Erythrocyte water content in spontaneously hypertensive rats and DOCA-salt hypertensive rats

Intra-erythrocyte water, sodium and potassium contents were measured in spontaneously hypertensive rats (SHR) and deoxycorticosterone acetate (DOCA)-salt rats. In 12 week old SHR, the intra-erythrocyte water content was slightly but significantly lower than that in age-matched Wistar-Kyoto (WKY) rats. SHR also exhibited a significantly lower intra-erythrocyte potassium content, but sodium content tended to be elevated. Although sodium content was not correlated with the water content, potassium content was. In DOCA-salt hypertensive rats, the intra-erythrocyte sodium content was higher than that in age-matched normotensive Sprague-Dawley rats by about 33%, but the water and potassium contents were similar. There were no significant correlations between these parameters. These findings provide no evidence of water retention in erythrocytes from DOCA-salt rat or SHR even though intra-erythrocyte sodium content was increased.     

EFFECT OF AN ANTIHYPERTENSIVE DRUG ON BRAIN ANGIOTENSIN II LEVELS IN RENAL AND SPONTANEOUSLY HYPERTENSIVE RATS

1. Although numerous studies suggest that brain angiotensin (AII) may play an important role in the regulation of blood pressure, it is still unclear what factors may influence brain All. In this study, we hypothesized that brain AII is influenced by circulating factors. To investigate the role of blood pressure and plasma All in brain AII level, we studied the effect of an antihypertensive drug on brain AII in two-kidney, one-clip (2K1C) and spontaneously hypertensive (SHR) rats. 2. Hydralazine (20mg/kg per day) and vehicle (water) were given to 2K1C rats between 2 and 6 weeks after operation and SHR for 4 weeks. In addition, vehicle was applied to sham operated rats and Wistar-Kyoto (WKY) rats. Brain and plasma AII was measured by a highly sensitive radioimmunoassay coupled with high performance liquid chromatography. 3. Hydralazine treatment effectively lowered blood pressure to the same levei of sham-operated and WKY rats. 2K1C rats showed significantly higher plasma All than sham rats, but hydralazine treatment did not show any change in plasma AII. Brain AII in the hypothalamus region of 2K1C rats showed a significantly higher level than sham rats. Interestingly, hydralazine treatment diminished this increase in brain AII. In contrast, SHR showed higher brain A11 levels in the hypothalamus, brainstem and cerebellum than in WKY rats, whereas there was no significant change in plasma AII concentration between SHR and WKY rats. In contrast to the results found in 2K1C rat experiments, hydralazine treatment failed to decrease brain AII levels despite lowered blood pressure. 4. In conclusion, brain AII is affected by systemic blood pressure in 2K1C hypertensive rats, but not in SHR, and the mechanisms which cause the difference between 2K1C rats and SHR are unknown in this study.