蛇床子素在兔体内药物代谢动力学

目的研究蛇床子素在兔体内的药物代谢动力学。方法用高效液相色谱法,以丹皮酚为内标,以甲醇-水(80∶20)为流动相,测定兔血液中蛇床子素(iv,10 mg·kg^-1)的含量。采用3P87程序计算药物代谢动力学参数。结果蛇床子素iv药代动力学符合二房室开放模型,T_1/2α=5.81 min,T_1/2β=42.2 min,K21=0.036 0·min^-1,K₁₂=0.045 0·min^-1,K₁₀=0.054 0·min^-1,AUC=235 mg·min·L^-1,CLs=0.043 0 L·min^-1·kg^-1,V_C=0.780 L·kg^-1。结论蛇床子素在兔体内分布及消除较快     

白杨素衍生物的合成和晶体结构及与DNA的作用

以白杨素为先导化合物经羟甲基化反应合成中间体5,7-二羟基-6,8-二羟甲基黄酮(1)，进而合成了5,7-二羟基-6,8-二(甲氧基甲基)黄酮(2)，5,7-二羟基-6,8-二(乙氧基甲基)黄酮(3)，5,7-二羟基-6,8-二(丁氧基甲基)黄酮(4)，5,7-二羟基-6,8-二(戊氧基甲基)黄酮(5)和5-羟基-7-甲氧基-6,8-二(乙氧基甲基)黄酮(6)；采用IR，¹H NMR，¹³C NMR和元素分析对1～6进行了表征，同时用X-射线单晶衍射法对6进行了晶体结构测定。利用荧光法分别对1～4与CT-DNA的作用进行了研究，根据Stern-Volmer方程，它们对EB-DNA体系的荧光猝灭常数分别为k_q1=9.71×10³ L·mol^-1，k_q2=2.25×10⁴L·mol^-1，k_q3=1.03×10⁴L·mol^-1和k_q4=7.96×10³ L·mol^-1。1～4与白杨素相比，对DNA更具亲和力，为开发更有效的黄酮类化合物提供了实验依据。     

一叶萩碱对5种神经递质受体和蛙脊髓膜电位的影响

Using radioligand binding assay method, securinine was shown to be specifically bound to GABA receptors of rat brain with IC₅₀ of 10^(-4)～10^-5mol/L. However, securinine did not exhibit affinity for a₁-, a₂- adrenoceptors and M-cholinergic receptors of rat brain and the β-adrenoceptors of duck erythrocyte membrane. In isolated and perfused bullfrog spinal cord experiment, the depolarization induced by GABA was slightly depressed by securinine (1 mmol/L), but no antagonistic effect on glycine or taurine evoked depolarization was observed with securinine. These results indicate that securinine is a weak GABA antagonist.     

LC-MS/MS法测定人血浆中西酞普兰及其在制剂生物等效性中的应用

A sensitive and selective LC-MS/MS method for determination of citalopram in human plasma was established to study the bioequivalence of different formulations containing citalopram. The samples were simply pretreated by protein precipitation using acetonitrile, and then analyzed on a Zorbax Extend C₈column. The mobile phase consisted of acetonitrile-water-formic acid (60∶40∶0.2), at a flow-rate of 0.5 mL·min^-1. A Thermo Finnigan TSQ Quantum Ultra tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring using the precursor to product ion combinations of m/z325 → m/z109 and m/z265 → m/z167 was performed to quantify citalopram and the internal standard, respectively. The pharmacokinetic parameters of citalopram in different formulations were calculated by non-compartment model. The linear calibration curves were obtained in the concentration range of 0.10-100 μg·L^-1. The lower limit of quantification was 0.10 μg·L^-1. The intra- and inter-day relative standard deviation (RSD) over the entire concentration range was less than 5.2%. Accuracy determined at three concentrations (0.25, 8.00 and 90.0 μg·L^-1 for citalopram) ranged from -4.7% to 1.3%. Each plasma sample was chromatographed within 3.0 min. The method was successfully used in bioequivalence study of citalopram in human plasma after oral administration of 20 mg citalopram. Calculated with AUC_{1-120 h}, the bioavailability of two formulations was (102.1±10.9)%. The method is rapid, selective, robust and is proved to be suitable for bioequivalence evaluation of different formulations containing citalopram.     

Monocyte and neutrophil direct counts correlate with C-reactive protein plasma concentration in patients with acute pancreatitis

Acute pancreatitis (AP) is associated with the intensive inflammatory response in white blood cells (WBC) and C-reactive protein (CRP). This paper presents the relationship between the CRP plasma concentration and the direct counts of peripheral WBC in AP during the initial five days. The study consisted of 56 patients with AP, 36 patients with mild form of AP and 20 patients with severe form of AP. ABX VegaRetic hematological analyzer was used to perform the count of blood cells, and the immunonephelometric method was performed to measure the CRP concentration levels. AP patients presented with WBC count values in the range of 3.2 − 22.4 × 10³/μl and CRP concentration levels in the range 3.3 − 599.8 mg/l. The WBC count correlates with CRP levels during the entire observation period. The relationship of CRP and WBC is expressed in the following regression equation: WBC (10³/μl) = 3.66 + 1.40 × log_eCRP (mg/l). The highest median neutrophil count (8.15 × 10³/μl) was observed on the first day. The count decreased to 5.27 × 10³/μl on the fifth day. The most substantial finding in this study involved the values found for the monocytes and CRP (r= 0.53; p<0.001). Day two and day three were the highest (r=0.59, p<0.001). On day two, the regression equation for this relationship is: Monocytes (10³/μl) = −0.34 + 0.21 × log_eCRP(mg/l). The correlation between direct monocyte count and plasma CRP concentration in AP reflect a CRP-dependent stimulation of IL-6 release from activated blood monocytes.     

γ-去氢骆驼蓬碱等咔啉类生物碱的辐射防护作用

γ- Harmine(Ⅰ),’harmine(Ⅱ )and harmaline(Ⅲ )were isolated from PeganumHarmala L.( Zygophylaceae).Tests were conducted with mice to detect whether γ- harmine( a newcompound), harmine,harmof(Ⅳ)and harmalol(Ⅴ) are effective radioprotective compounds againstγ-ray irradiation, Intraperitoneal injection of the hydrochlorides of the four alkaloids 50～80mg·kg^-1×1 in NIH male mice 30～45 minutes before 8.6～9. 7 Gy whole body ⁶⁰Co irradiationsignificantly increased the survival effects(1. 33～2. 61)and 30-day survivai rate in comparison withcontrol mice.The results indicatethat γ- harmine exhibited relatively good radioprotective effect.γ-harmine is the first alkaloid isolated from a plant having ptotective effects against whole-body lethal irradiation in mice.     

Histaprodifen, methylhistaprodifen, and dimethylhistaprodifen are potent H1-receptor agonists in the pithed and in the anaesthetized rat

Selective H₂- and H₃-receptor agonists, exhibiting an at least tenfold higher potency than histamine itself at the respective receptors, have been known for several years. Selective H₁-receptor agonists with a potency exceeding that of histamine have become available only recently; the most potent are methylhistaprodifen and dimethylhistaprodifen [N ^α-methyl- and N ^α,N ^α-dimethyl-2-(3,3-diphenylpropyl)histamine, respectively] with 3.4- and 2.4-fold higher potencies than histamine in vitro (in the guinea-pig ileum). The aim of the present study was to examine whether these compounds and the parent compound histaprodifen are potent H₁-receptor agonists in the pithed and in the anaesthetized rat. In pithed, vagotomized rats diastolic blood pressure was decreased by 2-(2-thiazolyl)ethanamine i.v. (which was used as a reference H₁-receptor agonist) and by histaprodifen, methylhistaprodifen, and dimethylhistaprodifen; the maximum decrease was about 45 mmHg for each compound, and the potencies, expressed as pED₅₀, the negative logarithm of the dose (in mole per kilogram body weight) eliciting a half-maximal response, were 7.23, 7.55, 8.43 and 8.12, respectively. The dose/response curves of the four compounds were shifted to the right to about the same extent by the H₁-receptor antagonist dimetindene (1 μmol/kg i.v.). The vasodepressor response was not affected by combined i.v. administration of the H₂- and H₃-receptor antagonists ranitidine and thioperamide, by combined i.v. administration of the α₁- and α₂-adrenoceptor antagonists prazosin and rauwolscine, and by the β-adrenoceptor antagonist propranolol i.v. but was attenuated by the inhibitor of NO synthase, N ^ω-nitro-l-arginine methyl ester i.v. In anaesthetized rats 2-(2-thiazolyl)ethanamine, histaprodifen, methylhistaprodifen and dimethylhistaprodifen i.v. also decreased diastolic blood pressure in a manner sensitive to dimetindene i.v. Our data show that histaprodifen and, in particular, methyl- and dimethylhistaprodifen are highly potent H₁-receptor agonists in vivo. Received: 3 September 1998 / Accepted: 23 October 1998     

八宝素在Beagle犬体内药代动力学

目的研究八宝素在Beagle犬体内的药代动力学。方法用高效液相色谱法，以蒽为内标，苯甲酰氯为衍生剂，甲醇-水(64∶36)为流动相，测定一次性静脉注射10.6和21.3 mg·kg^-1八宝素后，Beagle犬血液中八宝素的含量。采用3P97程序计算药物代谢动力学参数。结果八宝素iv在Beagle犬体内的药代动力学符合二室开放模型，两剂量组t^1/2α为2.3和2.1 min， t_1/2β分别为1.9和2.0 h， v_s均为0.54 L·kg^-1， AUC分别为1.8和4.1 g·min·L^-1，CL分别为0.004 8和0.005 6 L·kg^-1·min^-1。结论八宝素在Beagle犬体内分布和消除较快,呈一级动力学特征。     

灯盏花素及其β-环糊精包合物在大鼠体内的药代动力学

目的建立测定大鼠血浆中灯盏乙素浓度的反相高效液相色谱法，研究灯盏花素及其β-环糊精包合物(灯盏花素-β-CD)大鼠灌胃后体内药代动力学行为。方法以甲醇-水-醋酸盐缓冲液为流动相，Shim-pack C₁₈为固定相；12只大鼠随机均分为2组，分别灌胃灯盏花素及其包合物后，检测血浆药物浓度。药时数据采用3P97药代计算程序处理。结果线性范围10-400 ng·mL^-1，方法回收率95.32%-98.81%；灯盏花素和包合物的C_max分别为(154±18) ng·mL^-1和(328±31) ng·mL^-1；AUC_0-12h分别为(710±126) ng·h·mL^-1和(1 093±200)ng·h·mL^-1，经t检验两者有极显著性差异(P<0.01)。结论该法准确、灵敏，适用于灯盏乙素血浆浓度的测定；制备的灯盏花素包合物与灯盏花素相比吸收显著增加。     

甲基黄酮醇胺盐酸盐对β受体的阻断作用

The β-receptor blocking action of methylflavonolamine hydrochloride(MFA) was studied and compared with those of propranolol. The doseresponse curves of isoproterenol were shifted to the right by MFA on isolated rabbit atrium in this experiment. The pA₂ value and the slope of the regression line of MFA calculated from Schild plot were 5.53 and -0.84 respectively. The effects of MFA and propranolol on duck erythrocyte membranes were studied by the radioligand binding method. Both MFA and propranolol inhibited the binding of [³H] dihydroalprenolol to β-receptors. Their apparent equilibrium dissociation constants were 1.12×10^-5 mol/L and 5.50×10^-9 mol/L respectively. The affinity of propranolol to β-receptors of duck erythrocyte membranes was 2039-fold higher than that of MFA. These results demonstrates that MFA is a weak competitive β-receptor blocking agent.     

PERTUSSIS TOXIN-SENSITIVE G-PROTEINS AND REGULATION OF BLOOD PRESSURE IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. Increased Gi-protein-mediated receptor-effector coupling in the vasculature of the spontaneously hypertensive rat (SHR) has been proposed as a contributing factor in the maintenance of elevated blood pressure. If increased Gi-protein-mediated activity plays an important role in hypertension in SHR, then inhibition of Gi-proteins by pertussis toxin would be expected to decrease blood pressure in this genetic hypertensive model. To address this hypothesis, studies were undertaken comparing the cardiovascular effects of pertussis toxin in SHR and normotensive Wistar-Kyoto (WKY) rats. 2. Spontaneously hypertensive and WKY rats were instrumented with radiotelemetry devices and blood pressure measurements were recorded in conscious rats. Following a single injection of pertussis toxin (10 micrograms/kg, i.v.), mean arterial blood pressure fell from 161 +/- 3 to 146 +/- 1 mmHg in the SHR and the effect was sustained for more than 2 weeks. In contrast, 10 micrograms/kg, i.v., pertussis toxin produced no significant effect on blood pressure in WKY rats (103 +/- 4 vs 101 +/- 5 mmHg). 3. In a separate study, SHR and WKY rats were administered 30 micrograms/kg, i.v., pertussis toxin or 150 microL/kg, i.v., saline and, 3-5 days later, rats were anaesthetized and instrumented to permit measurement of blood pressure and renal function. At this higher dose, pertussis toxin reduced blood pressure in both strains of rat, although the effect was markedly greater in SHR (approximately 40 mmHg decrease) compared with WKY rats (approximately 15 mmHg decrease). In SHR, pertussis toxin increased renal blood flow (from 5.7 +/- 0.3 to 7.5 +/- 0.8 mL/min per g kidney) and decreased renal vascular resistance (from 31 +/- 2 to 19 +/- 2 mmHg/mL per min per g kidney). In WKY rats, pertussis toxin had no significant effect on renal parameters. 4. Results from these studies indicate that a pertussis toxin-sensitive Gi-protein-mediated pathway contributes to the maintenance of hypertension and elevated renal vascular tone in the SHR.     

Different effects of aspirin on blood pressure of spontaneously hypertensive rats (SHR) with high and spontaneously low levels of blood pressure.

Spontaneously hypertensive rats (SHR) of the Okamoto strain with blood pressure above 161 mmHg and SHR with blood pressure levels of less than 160 mmHg were treated with oral doses of aspirin (100 mg kg-1) for three days. Whereas the blood pressure of SHR with blood pressure above 161 mmHg was decreased by aspirin, the blood pressure of SHR below 160 mmHg was increased by aspirin. The extent and direction of blood pressure change by aspirin was strongly correlated with the blood pressure of SHR before treatment (r = -0.88). The effect of aspirin supports an important role for endogenous prostanoids in the regulation of blood pressure of SHR.     

MESENTERIC RESISTANCE AND BRAIN MICROVASCULAR ANGIOTENSIN-CONVERTING ENZYME IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. Angiotensin-converting enzyme (ACE) concentration was measured in mesenteric and brain microvessels from spontaneously hypertensive rats (SHR) and compared with normotensive controls using a specific radioligand binding assay. 2. Plasma angiotensin-converting enzyme activity was similar in SHR (n = 15) and normotensive controls (n = 21; 58 +/- 1 nmol HL/mL per min, vs 64 +/- 6 nmol HL/mL per min). 3. There was no significant difference between the mesenteric vascular angiotensin-converting enzyme radioligand binding site density (Bmax, fmol/mg protein) of SHR and normotensive controls (954 +/- 77 vs 890 +/- 56, P = 0.5, unpaired Student's t-test), despite significant differences in systolic blood pressure (220 +/- 8 mm Hg vs 120 +/- 6 mm Hg respectively, P less than 0.01) and increased mesenteric wet weight to bodyweight ratio in the hypertensive rats (0.28 +/- 0.02 mg/g, n = 5 vs 0.16 +/- 0.02 mg/g, n = 7, P less than 0.01). 4. Brain vascular angiotensin-converting enzyme radioligand binding site density (Bmax, fmol/mg protein) was also similar in SHR and normotensive controls (467 +/- 62, n = 5 vs 497 +/- 64, n = 5, P = 0.7, unpaired Student's t-test). 5. These results demonstrate that vascular angiotensin-converting enzyme concentration is not altered in the SHR and that vascular ACE is not increased in this form of vascular hypertrophy or regulated by the blood pressure level.     

HYPOTENSIVE EFFECTS OF CAPTOPRIL ADMINISTERED CENTRALLY IN INTACT CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS AND PERIPHERALLY IN ANEPHRIC ANAESTHETIZED SPONTANEOUSLY HYPERTENSIVE RATS

1. The hypotensive response to captopril in anaesthetized spontaneously hypertensive rats (SHR) is not modified by bilateral nephrectomy performed 1 or 24 h previously. 2. Intracerebroventricular injection (i.c.v.) of captopril (2 mg kg^?1) significantly lowered blood pressure of conscious SHR over a 7-h period of observation but there was no significant blood pressure response to i.c.v. vehicle, or to intravenous captopril (2 mg kg^?1) in SHR. 3. There was no significant blood pressure response to captopril (2 mg kg”') i.c.v. in the normotensive Wistar Kyoto controls (NT-WK). 4. These results indicate that captopril can lower the blood pressure of SHR by mechanisms independent of the kidneys or the circulating renin-angiotensin system. 5. The hypotensive effect of central captopril in SHR but not in the NT-WK suggests biochemical differences between the brains of the two rat strains.     

TIME COURSE OF CHANGES IN BARORECEPTOR REFLEX CONTROL OF HEART RATE IN CONSCIOUS SHR AND WKY: CONTRIBUTION OF THE CARDIAC VAGUS AND SYMPATHETIC NERVES

1. The aim of this study was to assess the vagal and sympathetic nerve contribution to the relationship between mean arterial pressure (MAP) and heart rate (HR) at 6, 9, 14 and 20 weeks of age in conscious Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) with methoxamine- and nitroprusside-induced steady-state changes in blood pressure. 2. MAP increased with age in both strains but was 17-23% higher in SHR. 3. By contrast baroreflex parameters (HR range: difference between upper and lower HR plateaus, and gain: average slope between inflection points of the logistic MAP-HR relationship) decreased with age in SHR but increased in WKY. 4. After methylatropine, no differences in the cardiac sympathetic baroreflex range or gain parameters were observed between strains or ages. 5. It was concluded that older SHR have normal sympathetic but reduced vagal capacity to control HR in response to changes in MAP, but that this deficit was not dependent on the absolute level of blood pressure. 6. Because the differences were confined to one effector, SHR may have different central rather than arterial baroreceptor afferent mechanisms.     

Antihypertensive effect of an endothelin receptor antagonist in DOCA-salt spontaneously hypertensive rats.

1. Endothelin-1 gene expression is enhanced in aorta and mesenteric arteries, and possibly other vessels, of deoxycorticosterone acetate (DOCA)-salt hypertensive rats but is normal or reduced in spontaneously hypertensive rats (SHR). Bosentan, a mixed ETA/ETB endothelin receptor antagonist, blunts the development of elevated blood pressure of DOCA-salt hypertensive rats but not in SHR. In this study we investigated whether treatment of DOCA-salt SHR with bosentan would result in blunted rise in blood pressure. 2. SHR, aged 13 weeks, were implanted with silastic containing DOCA and offered 1% saline to drink. Systolic blood pressure was measured by the tail-cuff method. Endothelin-1 mRNA abundance in aorta and mesenteric arteries was measured by Northern blot analysis. Content of immunoreactive endothelin in blood vessels was measured by radioimmunoassay. 3. Systolic blood pressure rose less in bosentan-treated DOCA-salt SHR (to 223 +/- 2 mmHg) in comparison to the untreated rats (241 +/- 1), a small but significant difference (P < 0.001). However, blood pressure of bosentan-treated DOCA-salt SHR was still higher than in age-matched SHR. Endothelin-1 mRNA abundance and content of immunoreactive endothelin were increased in the aorta and the mesenteric arterial bed of DOCA-salt SHR, and were unaffected by treatment with bosentan. 4. These data support the hypothesis of a role of endothelin-1 in blood pressure elevation in this hypertensive model with malignant hypertension. They also support the hypothesis that an antihypertensive effect of the mixed ETA/ETB endothelin receptor antagonist, bosentan, is found when experimental hypertensive animals exhibit enhanced endothelin-1 gene expression in blood vessels.     

BLOOD PRESSURE AND LIFESPAN FOLLOWING BRIEF ACE INHIBITOR TREATMENT IN YOUNG SPONTANEOUSLY HYPERTENSIVE RATS

1. Brief treatment with angiotensin-converting enzyme (ACE) inhibitors in young spontaneously hypertensive rats (SHR) causes a reduction in blood pressure that persists into maturity. The lifetime effects of such treatment have not been studied. 2. Nineteen male SHR were treated with either water (n= 9) or perindopril (3 mg/ kg per day) (n = 10) by daily gavage between 6 and 10 weeks of age and systolic blood pressure and bodyweight were measured each month until all animals died in old age. 3. Following treatment the systolic blood pressure of SHR treated with perindopril remained consistently lower than control SHR until about 82 weeks of age. After this age the blood pressure of control SHR fell spontaneously so that smaller differences were observed between the two groups in the last 4 months of the study. 4. Rats that received perindopril lived on average 1 month longer than control rats, but this difference was not statistically significant. 5. Thus, brief ACE inhibition in early life in SHR ameliorated the hypertension throughout life.     

VASCULAR SMOOTH MUSCLE POLYPLOIDY IN THE DEVELOPMENT AND REGRESSION OF HYPERTENSION

1. Two groups of spontaneously hypertensive rats (SHR) were treated with enalapril (25-30 mg/kg per day): Group I received treatment from 4 to 14 weeks of age to inhibit development of hypertension and Group R received the drug from 14 to 20 weeks of age to reverse established hypertension. 2. Systolic blood pressure, ploidy of aortic smooth muscle cells (flow cytometric DNA analysis) and aortic hypertrophy (medial cross-sectional area) were determined at times both during and after enalapril treatment (up to 30 weeks). 3. Enalapril treatment normalized blood pressure to that of age-matched Wistar-Kyoto rats in both groups. Blood pressure rose again following cessation of treatment. 4. In untreated SHR the incidence of polyploid cells increased concomitantly with increasing pressure throughout the time studied, whereas in Group I the incidence remained low. In Group R, the incidence of polyploidy directly paralleled both the decrease (normalization) and the rise in blood pressure following cessation of treatment. 5. Hence, the incidence of vascular smooth muscle cell polyploidy is not simply a result of growth of the vessel with increasing age of the SHR, but parallels inhibition, reversal, and redevelopment of hypertension.     

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.     

BLOOD PRESSURE, SALT APPETITE AND MORTALITY OF GENETICALLY HYPERTENSIVE AND NORMOTENSIVE RATS MAINTAINED ON HIGH AND LOW SALT DIETS FROM WEANING

1. Blood pressure, bodyweight, saline preference and mortality rate were examined in spontaneously hypertensive rats (SHR) of the Okamoto strain and normotensive control Wistar-Kyoto (WKY) rats maintained on low (0.1% NaCl w/w), control (0.8% w/w) and high (3% w/w) salt diets from weaning until 6 months of age. 2. The growth rate of SHR on high salt diet was not significantly different from that on control diet but SHR maintained on a low salt diet exhibited a markedly reduced growth rate. While the growth rate of WKY on low salt diet was not significantly different from that on control diet, the bodyweights of WKY on high salt diet were significantly greater than those of animals on control diet. 3. While low salt diet markedly attenuated the development of hypertension in the SHR, high salt diet significantly exacerbated the blood pressure of this strain. Neither high nor low salt diet altered the blood pressure of WKY. 4. SHR on high and low salt diets had an increased mortality rate compared with SHR on control salt diet but these differences were of slight statistical significance. Conversely, WKY on all three diets exhibited similar mortalities over the 6-month observation period. There were no significant differences in mortalities between SHR and WKY on any diet. 5. The preference for 0.9% saline, when offered as a choice with water, was not significantly different between SHR on the different diets. WKY on high salt diet, however, exhibited a significantly reduced preference for saline over the 10-day test period compared with animals on control or low salt diet. 6. Thus dietary salt modulates the hypertension of SHR but not the blood pressure of WKY. SHR would appear to require more dietary sodium for normal growth and perhaps full expression of its hypertension. The higher and lower blood pressures of the SHR on high and low salt diet, respectively, were associated with increased mortality, which was a trend not seen in the WKY.