Effects of hydroxyfasudil administered to the nucleus tractus solitarii on blood pressure and heart rate in spontaneously hypertensive rats

Previously, we reported that the inhibition of Rho-kinase by a microinjection of Y-27632 or the transfection of dominant-negative Rho-kinase into cells of the nucleus tractus solitarii (NTS) reduces blood pressure, heart rate, and sympathetic nerve activity. In the present study, we examined the effects of another Rho-kinase inhibitor, hydroxyfasudil, on blood pressure and heart rate in anesthetized rats. The results were compared between normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The microinjection of hydroxyfasudil was performed unilaterally or bilaterally into the NTS of WKY rats and SHR. A unilateral microinjection of hydroxyfasudil elicited depressor and bradycardic responses in SHR but not in WKY rats. A bilateral microinjection of hydroxyfasudil elicited depressor and bradycardic responses in both SHR and WKY rats. However, the magnitude of the decrease in these variables was greater in SHR than in WKY rats. The expression levels of RhoA in the membrane fraction and phosphorylated ERM family (ezrin, radixin, and moesin) in the NTS were greater in SHR than in WKY rats. These results suggest that the microinjection of hydroxyfasudil into the NTS causes cardiovascular responses similar to those caused by Y-27632 and that these responses are probably mediated by the inhibition of Rho-kinase.     

Synergism of hydrochlorothiazide and nifedipine on blood pressure variability reduction and organ protection in spontaneously hypertensive rats

This study was designed to investigate the effects of a hydrochlorothiazide-nifedipine combination on blood pressure (BP), blood pressure variability (BPV), baroreflex sensitivity (BRS), and organ protection in spontaneously hypertensive rats (SHR). The doses used were 10 mg/kg/d for both hydrochlorothiazide and nifedipine, and 10+10 mg/kg/d for the combination of these two drugs. Drugs were mixed into rat chow at the aforementioned doses. SHR were treated for 4 months, and then BP was continuously recorded for 24 h. After the determination of BRS, rats were killed for organ-damage evaluation. It was found that long-term treatment with hydrochlorothiazide, nifedipine or both significantly decreased BP and BPV, enhanced BRS and conferred organ protection in SHR. The combination of hydrochlorothiazide and nifedipine had a significant synergistic effect on BPV reduction, BRS enhancement and organ protection in SHR, whereas no obvious synergism on BP reduction was found. Multiple-regression analysis showed that the decrease in left ventricular and aortic hypertrophy was most closely associated with the decrease in systolic BPV and the increase in BRS, and the amelioration of renal lesions was most closely associated with the increase in BRS. In conclusion, long-term treatment with a combination of hydrochlorothiazide and nifedipine yielded a significantly synergistic effect on BPV reduction, BRS restoration and organ protection in SHR. In addition to BP reduction, the decrease in BPV and the enhancement of BRS may have made important contributions to the observed organ protection.     

Tyrosine administration reduces blood pressure and enhances brain norepinephrine release in spontaneously hypertensive rats.

Administration of L-tyrosine to normotensive or spontaneously hypertensive rats reduces blood pressure. The effect is maximal within 2 hr of injection. In spontaneously hypertensive rats, a dose of 50 mg/kg, intraperitoneally, reduces blood pressure by about 12 mm Hg (1 mm Hg = 1.33 x 10(2) pascals); a dose of 200 mg/kg produces the maximal effect, a reduction of about 40 mm Hg. Tryptophan injection (225 mg/kg) also lowers blood pressure in spontaneously hypertensive rats, but only by about half as much as an equivalent dose of tyrosine. Other amino acids tested (leucine, isoleucine, valine, alanine, arginine, and aspartate) do not affect blood pressure. Tyrosine injection appears to reduce blood pressure via an action within the central nervous system, since the effect can be blocked by co-administering other large neutral amino acids that reduce tyrosine's uptake into the brain. That tyrosine's antihypertensive action is mediated by an acceleration in norepinephrine or epinephrine release within the central nervous system is suggested by the concurrent increase that its injection produces in brain levels of methoxyhydroxyphenylethylglycol sulfate.     

Effects of verapamil and nifedipine on systemic hemodynamics in spontaneously hypertensive rats

Verapamil (1 mg/kg, i.v.) and nifedipine (0.3 mg/kg, i.v.) were tested at equi-antihypertensive doses for systemic hemodynamic responses in conscious spontaneously hypertensive rats (SHR) using the Fick method. Systemic hemodynamic effects of these agents were also evaluated in areflexic, spinal cord-transected and vagotomized SHR using the electromagnetic flowmetry technique. Both verapamil and nifedipine lowered mean arterial pressure (MAP:verapamil = -24%; nifedipine = -28%) in conscious SHR by decreasing total peripheral resistance (TPR:verapamil = -48%; nifedipine = -59%) with a concomitant rise in cardiac output (CO: verapamil = 48%; nifedipine = 86%) and stroke volume (SV:verapamil = 54%; nifedipine = 65%), but verapamil prevented tachycardia, whereas nifedipine increased heart rate (HR:13%). Verapamil and nifedipine also altered systemic hemodynamics in the areflexic SHR; verapamil reduced MAP (-31%) by reducing CO (-18%) with associated bradycardia (-25% HR), whereas nifedipine also lowered MAP (-21%) by decreasing TPR (-18%) without changes in CO and HR. It is concluded that, firstly, the antihypertensive action of verapamil and nifedipine in conscious SHR is due to systemic vasodilation that is associated with reflexly increased CO; secondly, that verapamil has a direct negative chronotropic effect, but nifedipine appears to be devoid of such an effect, and finally that the ability of verapamil to decrease TPR may depend upon resting sympathetic tone.     

Effects of NG-nitro-L-arginine on the blood pressure of spontaneously hypertensive rats with different degrees of hypertension.

The effects of NG-nitro-L-arginine (L-NNA) on blood pressure of various strains of spontaneously hypertensive rats were studied. Blood pressure of the rats was higher in the order of WKY, SHR, SHRSP, M-SHRSP. L-NNA caused an elevation of the blood pressure, which was greatest in SHR and smallest in WKY and M-SHRSP. Endothelium-dependent relaxation of aortae by acetylcholine was greatest in preparations from WKY and it decreased as the blood pressure of rats increased. Phenylephrine (higher than 10(-6) mg/kg) caused an elevation of the blood pressure, which was greatest in SHR and smallest in M-SHRSP. It was suggested that L-NNA elevated blood pressure by inhibiting the basal or flow-induced release of nitric oxide from the endothelium that is causing a reduction in vascular smooth muscle tone. The smaller effect of L-NNA in WKY was due to weak smooth muscle tone, while the smaller effect in SHRSP and M-SHRSP is due to impaired function of endothelium.     

钩藤总碱与天麻素联用对自发性高血压大鼠血压和血压变异性的影响

背景钩藤和天麻是治疗高血压的传统中药,常联合应用。目的研究钩藤、天麻的活性成分钩藤总碱及天麻素抗高血压和改善血压变异性的协同作用。方法 60只自发性高血压大鼠随机分为11组,分别是:对照组、钩藤总碱4组(25、50、100、200mg/kg)、天麻素3组(8、80、800mg/kg)、钩藤总碱+天麻素3组[(50+8)、(50+80)、(50+800)mg/kg],腹腔给药。采用清醒自由活动大鼠血压测定系统监测给药前后大鼠的血压和血压变异性。用两因素多水平析因设计、概率和法和q检验方法评价钩藤总碱和天麻素降压以及改善血压变异性的协同作用。结果在25～200mg/kg剂量范围内,钩藤总碱给药量与血压降低幅度有量效关系。其中,200mg/kg剂量组给药前后收缩压分别为(182±16)和(142±12)mmHg,舒张压分别为(133±21)和(100±19)mmHg,给药前后血压平均值的差异有统计学意义(P<0.01)。天麻素单独注射剂量达到800mg/kg也没有降低自发性高血压大鼠的血压。而钩藤总碱+天麻素组[(50+8)、(50+80)、(50+800)mg/kg]有降压作用,钩藤总碱和天麻素联用具有协同降压作用,对血压变异性没有不良影响。结论钩藤总碱具有确切的降压作用,但对血压变异性没有影响。天麻素本身不降低血压,但与钩藤总碱联用具有协同降压作用。     

Effect of chronic ethanol consumption upon cardiovascular reactivity, heart rate and blood pressure in spontaneously hypertensive and Wistar-Kyoto rats.

OBJECTIVE: Clarification of the effect of chronic ethanol consumption upon cardiovascular reactivity in rats. DESIGN: Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) normotensive rats were randomly allocated in groups of 10 to ethanol in tap water [20% (v:v) after the first week or tap water for 7-12 weeks]. METHODS: Intra-arterial blood pressure and heart rate were measured at rest and in response to vibration and noise stress. Vascular reactivity was assessed in isolated paired perfused hindquarters and in mesenteric arterioles in a Mulvany-Halpern myograph. RESULTS: Resting intra-arterial blood pressure but not heart rate was lower in both ethanol-treated groups. The ethanol treatment increased the SHR heart rate response to sudden noise but the WKY response did not increase. Pressor responses to noise were initially greater in the ethanol-treated SHR. The ethanol had no effect upon isolated perfused hindquarter resistance at maximal dilation, dose-response curves in response to noradrenaline or vasopressin, or maximal contractile strength. Isolated mesenteric arterioles showed that ethanol had no effect upon responses to nerve stimulation or upon the 50% effective dose required for a response to noradrenaline or vasopressin. CONCLUSIONS: Ethanol treatment heightened the heart rate reactivity to stress without substantially affecting vascular neuro-effector characteristics in SHR. This is likely to be a central effect, caused by suppression of the central nervous inhibitory systems that influence the heart rate and baroreflex activity in a strain of rat already showing evidence of an impaired ability to modulate the heart rate and blood pressure in response to stress. The small reduction in resting blood pressure may be a consequence of the lower weight in the ethanol-treated rats, and/or may reflect a direct depressing action by the alcohol on vascular and cardiac muscle. These findings are discussed in the context of ethanol-induced hypertension in humans and possible genetic variations in central nervous, cardiac and vascular effects.     

吡格列酮配合生活方式干预对自发性高血压大鼠血压的影响

目的 评价胰岛素增敏剂吡格列酮(PIO)配合生活方式干预对自发性高血压大鼠(SHR)的降压作用.方法 35只SHR随机分为3组(SHR对照组,PIO用药组及PIO配合生活方式干预组),药物添加到大鼠饮水中,生活方式干预为每日减少投食量并游泳6～15 min,周期为12 w,采用间接方法测量血压.结果 PIO及配合生活方式干预组大鼠饮食控制良好,游泳能力逐渐增强,无意外死亡.PIO有良好的降压效果,药物配合生活方式干预降压效果更佳,体重控制良好.结论 PIO及配合生活方式干预具有良好的降低SHR血压效果,生活方式干预可作为纠正胰岛素抵抗(IR)的方法之一应用到高血压的治疗当中.     

Autonomic control of the diurnal variation in arterial blood pressure and heart rate in spontaneously hypertensive and Wistar-Kyoto rats

The relative influences of sympathetic and parasympathetic neural modulation on mean arterial pressure (MAP) and heart rate (HR), and their respective variabilities, were studied in young spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). An on-line computerized system was used for continuous intra-arterial measurements of MAP and HR in unrestrained rats. In addition, the autonomic nervous control of MAP and HR was studied in ageing SHR and WKY. Both WKY and SHR showed diurnal rhythms with regard to MAP and HR. The MAP variability was higher in SHR than in WKY during both daytime (inactive) and night-time (active), and did not change in response to either beta 1-adrenoceptor- or cholinergic blockade. Structural vascular changes, with a resultant increase in reactivity, may explain the elevated MAP variability in SHR. HR variability was clearly reduced in SHR; this was not influenced by vagal blockade, whereas HR variability was significantly reduced in WKY. This pattern is suggested to be due to a reduced tonic vagal discharge in SHR, as part of a persistent, mild defence reaction. The initial reduction in vagal activity will in turn eliminate vagally mediated tachycardias. Furthermore, administration beta 1-blockade to SHR of different ages caused a greater fall in MAP and HR than in WKY, indicating an increased dependence upon the sympathetic nervous system in SHR with age.     

Thromboxane synthesis and blood pressure in spontaneously hypertensive rats

The present study examines effects of administration of OKY 046, an inhibitor of thromboxane synthesis, for 100 days on systemic blood pressure and renal function in spontaneously hypertensive rats and in normotensive control rats. Untreated spontaneously hypertensive rats had higher values for thromboxane excretion in the urine and higher values for blood pressure than did normotensive control rats. Administration of OKY 046 decreased systolic and mean arterial blood pressure and urinary excretion of thromboxane and protein in spontaneously hypertensive rats. Administration of OKY 046 decreased thromboxane excretion in the urine of normotensive control rats but had no effect on blood pressure or protein excretion. Renal function, as assessed by the clearances of inulin and p-aminohippuric acid, was greater in spontaneously hypertensive rats treated with OKY 046 than in those receiving vehicle alone. In normotensive control rats, OKY 046 administration did not affect renal function. These results suggest that increased renal synthesis of thromboxane may play a role in the pathogenesis of the elevated blood pressure of spontaneously hypertensive rats.     

坎地沙坦对高血压患者窦性心率震荡现象的影响

目的观察高血压患者的窦性心率震荡（HRT）现象及坎地沙坦治疗对其的影响。方法应用24 h动态心电图比较2级以上原发性高血压患者（治疗组）治疗（8-16 mg坎地沙坦,每日1次）前后及健康对照者（对照组）的HRT指标[震荡初始（TO）、震荡斜率（TS）]的变化。结果与对照组相比,治疗组TO升高,TS降低（P〈0.01）。治疗组治疗后血压明显下降,TO降低,TS升高（P〈0.01或〈0.05）。结论高血压患者HRT现象明显减弱,提示存在自主神经功能受损;坎地沙坦可有效降压,并可改善高血压患者的自主神经功能。     

Effects of dietary sodium and fish oil on blood pressure development in stroke-prone spontaneously hypertensive rats.

The postulated antihypertensive effect of dietary fish oil and the influence of dietary sodium on this effect were evaluated in young stroke-prone spontaneously hypertensive rats (SHRSP) by direct intra-arterial measurement of blood pressure. Weaning rats were fed synthetic diets containing olive oil or eicosapentaenoic acid-enriched fish oil (5% of dry weight) with normal (0.23%) or high (2.8%) sodium content. Catheters were implanted after 3 months for blood pressure measurement under resting conditions and to sample blood for catecholamine determinations. Effects of fish oil on vascular reactivity were assessed in the in situ blood-perfused mesentery. The overall observation, from a series of experiments, was that feeding diets containing 5% fish oil to young SHRSP resulted in a small but consistent suppression of the development of hypertension. This effect could be counteracted, however, by increasing dietary sodium intake. Observations after ganglion blockade indicate that the antihypertensive effect of fish oil is unlikely to result from a reduction in sympathetic vascular tone.     

Effects of continuous intermedin infusion on blood pressure and hemodynamic function in spontaneously hypertensive rats

Objective To examine the effects of exogenously administered intermedin (IMD, adrenomedullin-2) on arterial blood pressure, cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive rats (SHRs) as well as to investigate the associated mechanisms. Methods Thirteen week-old male rats were divided in Wistar Kyoto (WKY) group (n = 12), SHR group (n = 12), IMD group (SHRs infused with IMD 1-47 500 ng/kg per hour, n = 12), and ADM group (SHRs infused with adrenomedullin 500 ng/kg per hour, n = 12). Results A two-week continuous administration of low dose IMD 1-47 via mini-osmotic pumps markedly reduced blood pressure, the maximal rates of increase and decrease of left-ventricle pressure development (LV ± dp/dtmax), left ventricular systolic pressure and heart rate in SHRs. Furthermore, IMD also inhibited protein over-expression of cardiovascular IMD receptors, myocardial Receptor Activity-Modifying Proteins (RAMP1 and RAMP2), aortic RAMP1, RAMP2, RAMP3, and calcitonin receptor-like receptor (CRLR); suppressed up-regulation of aortic RAMP1, RAMP2, RAMP3 and CRLR gene expression; and markedly elevated the mRNA abundance of myocardial atrial natriuretic peptide (ANP) and myocardial brain natriuretic peptide (BNP). Additionally, IMD 1-47 administration in SHRs increased aortic cAMP concentration and reduced myocardial cAMP concentration. Conclusion These findings support the speculation that IMD, as a cardiovascular active peptide, is involved in blood pressure reduction and cardiac function amelioration during hypertension. The mechanism underlying this effect may involve IMD binding of a receptor complex formed by RAMPs and CRLR, and consequential regulation of cAMP levels and other cardiovascular active factors, such as ANP and BNP.     

Comparison of valsartan and amlodipine on ambulatory blood pressure variability in hypertensive patients

We tested the hypothesis that calcium channel blockers (CCBs: amlodipine group, n = 38)) are superior to angiotensin receptor blockers (ARBs: valsartan group, n = 38) against ambulatory blood pressure variability (BPV) in untreated Japanese hypertensive patients. Both drugs significantly reduced ambulatory systolic and diastolic BP values. With regard to BPV, standard deviation (SD) in SBP did not change with the administration of either drug, but the ARB significantly increased SD in awake DBP (12 ± 4–14 ± 4 mmHg). The ARB also significantly increased the coefficients of variation (CVs)in awake and 24-h SBP/DBP (all P < 0.05), but amlodipine did not change the CV. CCB significantly reduced the maximum values of awake SBP (193 ± 24–182 ± 27 mmHg, P = 0.02), sleep SBP (156 ± 18–139 ± 14 mmHg, P < 0 .001), and awake and sleep DBP (P < 0.01 in both cases), but the ARB did not change the maximum BP values. In conclusion, a once-daily morning dose of CCB amlodipine was more effective at controlling ambulatory BPV than ARB valsartan, especially in reducing maximum BP levels.     

Effect of dietary calcium supplements and amlodipine on growth, arterial blood pressure, and cardiac hypertrophy of spontaneously hypertensive rats

It has been shown that calcium-enriched diets cause a decrease in arterial blood pressure in hypertensive patients and animals. Moreover, it has been suggested that the combination of dietary calcium and calcium antagonists could paradoxically have a synergistic effect in order to decrease arterial blood pressure. The combination of these treatments may also have potential therapeutic benefit in the attenuation of cardiac hypertrophy. In this study, after being weaned at three weeks, male spontaneously hypertensive rats (SHR) were randomized in four groups of animals. Two of these groups were fed on a normal calcium diet (Ca 1%) and another two groups were fed on a calcium-enriched diet (Ca 2.5%). One of the groups fed on each diet also received amlodipine (1 mg/kg/day) in the drinking water after being weaned. Body weight was measured weekly in all the groups, and arterial blood pressure was also measured in all the 10-, 15-, 20-, and 25-week-old SHR by the tail cuff method. We established the ratio heart weight/body weight x 1000 (R), and we weighed the left ventricle in the 25-week-old animals at the end of the different treatments. The Ca 2.5% diet caused a delay in the development of hypertension in SHR. This effect could not be correlated with alterations in body weight since this diet improved growth in these rats. Amlodipine did not alter growth in SHR. This pharmacological treatment caused a decrease in the arterial blood pressure of the SHR and it intensified the antihypertensive effect of the Ca 2.5% diet. Nevertheless, this drug attenuated the effect of dietary calcium on body weight and when the treatment was prolonged, almodipine also antagonized the effect of dietary calcium on arterial blood pressure. At the end of the different treatments the ratio R and the left ventricular weight were similar in all the groups of animals. Therefore, the use of dietary calcium with a calcium antagonist to control arterial blood pressure seems not to be advisable, and the present data do not prove the usefulness of the mentioned antihypertensive treatments in preventing cardiac hypertrophy.     

缬沙坦对自发性高血压大鼠血压和肾素-血管紧张素水平的对照研究

目的:动物实验观察缬沙坦的降压效果及其对血浆肾素活性和血管紧张素Ⅱ的影响.方法:24只雄性14周龄的SHR分为生理盐水组、苯那普利组、小剂量缬沙坦和大剂量缬沙坦组,另用6 只同龄雄性WKY大鼠对照.观察用药4周前后的血压、肾素活性和血管紧张素Ⅱ水平.结果:与生理盐水组、苯那普利组比较,缬沙坦的降压效果明确;大剂量缬沙坦平均下降41.7±4.93 mmHg,明显大于小剂量组的降压幅度27.7±4.46 mmHg,(P <0.01).SHR与WKY大鼠比较,血浆肾素活性仅在大剂量缬沙坦组明显升高;血管紧张素Ⅱ水平,大剂量缬沙坦组更为明显升高,而苯那普利组有所下降.结论:缬沙坦的降压效果优于苯那普利,苯那普利使血浆AngⅡ水平减低,而缬沙坦使血浆AngⅡ水平升高.在长期用药过程中,较高的血浆AngⅡ水平对人体的影响或对器官的影响如何,尚待进一步研究.     

缬沙坦对自发性高血压大鼠血压和肾素—血管紧张素水平的对照研究

目的：动物实验观察缬沙坦的降压效果及其对血浆肾素活性和血管紧张素Ⅱ的影响。方法：２４只雄性１４周龄的ＳＨＲ分为生理盐水组、苯那普利组、小剂量缬沙坦和大剂量缬沙坦组,另用６只同龄雄性ＷＫＹ大鼠对照。观察用药４周前后的血压、肾素活性和血管紧张素对水平。结果：与生理盐水组、苯那普利组比较,缬沙坦的降压效果明确;大剂量缬沙坦平均下降 ４１． ７±４． ９３ ｍｍＨｇ,明显大于小剂量组的降压幅度 ２７． ７±４． ４６ ｍｍＨｇ,（Ｐ＜０．０１）。 ＳＨＲ与ＷＫＹ大鼠比较,血浆肾素活性仅在大剂量缬沙坦组明显升高;血管紧张素Ⅱ水平,大剂量缬沙坦组更为明显升高,而苯那普利组有所下降。结论：缬沙坦的降压效果优于苯那普利,苯那普利使血浆ＡｎｇⅡ水平减低,而缬沙坦使血浆ＡｎｇⅡ水平升高。在长期用药过程中,较高的血浆 Ａｎｇ Ⅱ水平对人体的影响或对器官的影响如何,尚待进一步研究。     

Effects of high-calorie diet on blood pressure and sodium retention in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats

Previous reports from our laboratory have documented that spontaneously hypertensive rats (SHR) have insulin resistance and that insulin resistance is enhanced by high-caloric diet (HCD) feeding. The aim of this study was to elucidate the effect of HCD on blood pressure and sodium retention in both SHR and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were divided into two groups. One group of rats was fed normal diet (ND). The other rats were fed HCD. After the 8-week feeding period, insulin suppression tests were performed. The animals were individually housed in metabolic cages for the last 2 days of the experiment. Food consumption was recorded for 24 h, and a 24-h urine was collected to calculate the sodium excretory ratio. In both strains, body weight was significantly increased by HCD feeding. Blood pressure was significantly elevated in SHR by HCD feeding, whereas that of WKY was not affected by HCD feeding. In both strains, steady-state plasma glucose (SSPG) during the insulin suppression test was higher in the HCD group than in the ND group. SSPG was consistently higher in SHR than in WKY treated with HCD. Urinary sodium excretion ratio was significantly decreased in SHR by HCD, and plasma potassium concentrations were significantly lower in SHR with HCD than in SHR with ND, whereas those of WKY were not affected by HCD feeding. SHR are more sensitive to the induction of insulin resistance than WKY, resulting in sodium retention and elevation of blood pressure.     

The effect of atrial natriuretic factor on blood pressure, heart rate, and renal functions in conscious, spontaneously hypertensive rats

Atrial natriuretic factors, polypeptides released by atrial myocytes, may play a role in the control of blood pressure and the regulation of renal salt and water excretion. Our studies were designed to assess the role of a synthetic peptide, atriopeptin II, on blood pressure and heart rate, renal hemodynamics, and salt and water excretion in conscious, spontaneously hypertensive rats and in normotensive Wistar-Kyoto rats. Changes in mean arterial pressure and heart rate were recorded following intravenous bolus injections (0.1, 1.0, 10, 100 micrograms/kg) of atriopeptin II in 5 spontaneously hypertensive and 5 Wistar-Kyoto rats. In a second group of rats the peptide was infused for 90 minutes in two different doses: low dose, 1 microgram/kg + 2 micrograms/kg/hr; and high dose, 10 micrograms/kg + 20 micrograms/kg/hr. Bolus injections of atriopeptin II resulted in dose-dependent decreases in mean arterial pressure in the hypertensive, but not in the normotensive, rats; heart rates remained unchanged. Blood pressure decreased gradually during the sustained infusion of both doses of atriopeptin II, with the spontaneously hypertensive strain showing increased sensitivity compared to the Wistar-Kyoto strain. Heart rate decreased in both strains during infusion of the high dose; the decrease was significant only in the hypertensive rats. The low dose of atriopeptin II increased the clearance of free water in both strains of rats; sodium excretion was increased only in the hypertensive rats. The high-dose atriopeptin II was associated with transient natriuresis, unaltered glomerular filtration rate, and decreased effective renal blood flow in both strains.(ABSTRACT TRUNCATED AT 250 WORDS)