A gene differentially expressed in the kidney of the spontaneously hypertensive rat cosegregates with increased blood pressure.

The role of the kidney in initiating hypertension has been much debated. Here we demonstrate that a recently identified gene of yet unknown function, termed SA, which is differentially expressed in the kidney of the spontaneously hypertensive rat, cosegregates with an increase in blood pressure in F2 rats derived from a cross of the spontaneously hypertensive rat with normotensive Wistar-Kyoto rats, accounting for 28 and 21% of the genetic variability in systolic and diastolic blood pressures, respectively. Further, the genotype at this locus appears to determine the level of expression of the gene in the kidney. The findings provide strong evidence for a primary genetic involvement of the kidney in hypertension.     

Genetic co-segregation of renal haemodynamics and blood pressure in the spontaneously hypertensive rat

1. To determine the relevance of renal circulatory abnormalities found in the immature spontaneously hypertensive rat (SHR) to the genetic hypertensive process, glomerular filtration rate and renal blood flow were measured in conscious F2 rats, derived from cross-breeding SHR and normotensive Wistar-Kyoto rats (WKY), at 4, 11 and 16 weeks of age by determining the renal clearances of 51Cr-ethylenediaminetetra-acetate and 125I-hippuran respectively. Plasma renin activity was measured at 11 and 16 weeks of age. 2. Mean arterial pressure, glomerular filtration rate and renal blood flow increased between 4 and 11 weeks of age. Between 11 and 16 weeks the mean glomerular filtration rate and renal blood flow did not alter, although the mean arterial pressure rose significantly. At 11 weeks of age, during the developmental phase of hypertension, a significant negative correlation between mean arterial pressure and both glomerular filtration rate and renal blood flow was noted. However, by 16 weeks when the manifestations of genetic hypertension were more fully expressed, no correlation between mean arterial pressure and renal blood flow or glomerular filtration rate was observed. Plasma renin activity was negatively correlated with both glomerular filtration rate and renal blood flow, but the relationship was stronger at 11 than at 16 weeks of age. 3. These results suggest that the reduction in renal blood flow and glomerular filtration rate, found in immature SHR, is genetically linked to the hypertension and may be of primary pathogenetic importance. It is proposed that the increased renal vascular resistance in these young animals stimulates the rise of systemic arterial pressure which returns renal blood flow and glomerular filtration rate to normal.     

Central effects of quinpirole on blood pressure of spontaneously hypertensive rats.

The i.v. administration of the dopamine D-2 receptor agonist quinpirole induced a rapid increase in blood pressure in spontaneously hypertensive rats (SHR). Heart rate showed little change. The pressor response to quinpirole was similar in SHR and normotensive Wistar-Kyoto rats (WKY) at doses of 0.03 to 0.3 mg/kg but, at 1 mg/kg, quinpirole induced a greater increase in blood pressure in SHR than in WKY. In contrast, although both strains showed a decreased locomotor activity after administration of 0.01 to 0.05 mg/kg of quinpirole, only in WKY was activity enhanced by 0.25 to 1.25 mg/kg of quinpirole. The i.v. administration of the dopamine agonists apomorphine, N-propylnorapomorphine and (R)-(+)-3-(3-hydroxyphenyl)-N-propylpiperidine, but not the putative presynaptic D-2 agonist (S)-(-)-3-(3-hydroxyphenyl)-N- propylpiperidine, induced pressor responses in SHR comparable to those after quinpirole administration. The pressor effect of quinpirole was enhanced by pretreatment with the peripheral D-2 antagonist domperidone, but blocked by the centrally acting dopamine antagonists haloperidol or sulpiride. In SHR, which were pretreated centrally with pertussis toxin, quinpirole induced a significantly smaller increase in blood pressure than in control SHR. Pretreatment centrally with 6-hydroxydopamine had no effect on the pressor action of quinpirole in SHR. Thirty minutes after i.v. administration of quinpirole, an additional injection of quinpirole did not significantly change blood pressure. Increasing the interval between two subsequent injections of quinpirole showed that this desensitization slowly reversed, but only after 24 hr had the pressor response to quinpirole fully recovered.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of heme arginate administration on blood pressure in spontaneously hypertensive rats.

Cytochrome P450 content and activities are increased in the kidneys of spontaneously hypertensive rats (SHR) as compared with those of normotensive, Wistar-Kyoto (WKY), control rats during the period of rapid elevation of blood pressure. We studied the effect of heme arginate, a potent inducer of heme oxygenase (EC 1.14.99.3), on microsomal cytochrome P450 levels and activities and blood pressure in SHR at 7 wk of age. Administration of heme arginate (15 mg/kg body weight for 4 d) resulted in a marked decrease in blood pressure from 156.3 +/- 4.7 to 129.8 +/- 4.5 mm Hg (P less than 0.001), whereas blood pressure in SHR receiving the vehicle control was not affected. The blood pressure of age-matched WKY was not affected by heme arginate. Heme oxygenase activity increased in both hepatic and renal microsomes of SHR and WKY by two- to four-fold after treatment with heme arginate. Maximal increase of heme oxygenase mRNA occurred 5-7 h after the last injection of heme arginate and returned to control levels after 24 h. The increase in heme oxygenase activity was associated with a parallel decrease in cytochrome P450 content and in the activity of cytochrome P450 omega/omega-1 arachidonate hydroxylases in kidneys of SHR. It is postulated that heme arginate treatment resulted in induction of heme oxygenase which consequently led to a diminution of cytochrome P450, especially the arachidonate omega/omega-1 hydroxylases leading to a marked decrease in 19-hydroxyeicosatetraenoic acid (HETE) and 20-HETE. The effect of heme arginate on blood pressure may be mediated via these biochemical events inasmuch as both 19-HETE and 20-HETE produced by the kidney may promote hypertension by causing vasoconstriction and sodium retention.     

Arterial wall renin and renal venous renin in the hypertensive rat.

1. Infusion of sufficient renin to raise the blood pressure of normal rats to hypertensive levels resulted in increased renin in the arterial wall. 2. Arterial wall renin and renal venous renin were normal in younger spontaneously hypertensive rats, but in older spontaneously hypertensive rats arterial wall renin was significantly increased and renal venous renin was significantly decreased. 3. Arterial wall renin in rats with either acute or chronic two-kidney Goldblatt renal hypertension was significantly increased, whereas circulatory renin was elevated in the former, but depressed in the latter. 4. Arterial wall renin may play a role in the maintenance of acute and chronic renal hypertension and also perhaps of spontaneous hypertension of long duration in older rats.     

茶皂甙对自发性高血压大鼠血压的影响研究

目的观察茶皂甙对自发性高血压大鼠血压的影响,为高血压治疗提供新的思路。方法24只雄性自发性高血压大鼠随机分为4组,每组6只:(1)高血压对照组;(2)卡托普利组(150 mg·kg-1·d-1);(3)茶皂甙高剂量组(1600 mg·kg-1·d-1);(4)茶皂甙低剂量组(400 mg·k-g1·d-1);6只雄性WKY大鼠作为正常血压对照组。每天通过灌胃法分别给予卡托普利,高、低剂量的茶皂甙和蒸馏水,每隔两周在上午8~10时用大鼠尾动脉血压无创测量分析系统测量大鼠动脉收缩压一次,共5次。结果给药8周后,茶皂甙高剂量组的动脉收缩压与用药前相比显著下降(P<0.01),明显低于高血压对照组(P<0.01),与卡托普利组接近(P>0.05),茶皂甙低剂量组的动脉收缩压与用药前相比也有一定程度的降低(P<0.05)。结论茶皂甙可以有效降低自发性高血压大鼠的动脉血压。     

Effect of antitonin on blood pressure in the one-kidney hypertensive rat.

1. The tonin concentration of saliva and submaxillary glands was studied in one-clip hypertensive rats with or without the contralateral kidney. 2. Salivary tonin concentration was elevated in one-kidney hypertensive rats, but not in one-kidney normotensive or two-kidney, one-clip hypertensive rats. In contrast, an elevated submaxillary gland tonin concentration was found only in uninephrectomized animals, whether normotensive or hypertensive. 3. A single intravenous administration of rabbit tonin antiserum into one-kidney hypertensive rats restored blood pressure to normal in seven out of ten animals. There was little change in blood pressure in two-kidney, one-clip hypertensive, uninephrectomized or sham-operated rats. 4. These findings suggest a connection between the physiology of the kidney and of the submaxillary gland in the rat, and indicate that tonin may play a significant role in maintaining high blood pressure in one-kidney hypertensive aniamls.     

Effects of metoprolol on blood pressure and plasma renin activity in thiazide-resistant hypertensive patients.

Twenty patients with mild to moderate hypertension whose blood pressures were not adequately controlled by a thiazide diuretic were treated for 4 wk with metropolol. Normotension (diastolic pressure less than 90 mm Hg) or reduction in diastolic pressure of at least 10 mm Hg was achieved in 12 of the patients 1 wk after metoprolol (200 mg/day) was added to the hydrochlorothiazide (100 mg/day) regimen. In the other 8 patients, pressure reduction was attained with larger doses (300 to 400 mg/day) of metoprolol. After 1 wk of combined therapy, heart rate decreased by 11% (p less than 0.001) and plasma renin activity (PRA) decreased 48% (p less than 0.001). The individual changes in mean blood pressure did not correlate with either the premetoprolol PRA level (r = 0.14) or the changes in PRA after metoprolol (r = 0.03) but did correlate with steady-state metoprolol plasma levels (r = 0.61, p less than 0.01). Pressure and heart rate reductions were sustained during the last 3 wk of combined therapy but the PRA decrease did not persist; levels gradually rose to near control by the fourth week. Urinary sodium excretion was not consistently changed on metoprolol therapy.     

肝细胞生长因子对自发性高血压大鼠血压的影响

背景：肝细胞生长因子是一种多功能生长因子，它能促进多种细胞生长与移行及各种组织器官的发生。在心血管系统，它具有抗凋亡、抗纤维化、促进内皮细胞损伤后修复作用，推测其可能具有降压效应。 目的：观察外源性肝细胞生长因子对自发性高血压大鼠血压、血管内皮系统和肾素-血管紧张素系统的影响并探讨其调节血压的可能机制。设计、时间及地点：随机对照动物实验，于2007—03／07在安徽医科大学第一附属医院心内科完成。材料：外源性肝细胞生长因子粉剂购于美国Peprotech公司，成年白发性高血压大鼠组和WKY大鼠，均14周龄，体质量200～250g。自发性高血压大鼠随机分为实验组和单纯自发性高血压大鼠组，WKY大鼠为正常对照组，每组12只。方法：实验组每间隔24h从尾静脉依次给予肝细胞生长因子5，10，15，20，25u玳g，自发性高血压大鼠组和正常对照组同时给予等量生理盐水。每次注射安抚大鼠5min后测血压与心率，最后一次注射后观察血压降至最低值时（约注射后30min），麻醉后处死，各取右心室血2mL。 主要观察指标：①观察肝细胞生长因子对自发性高血压大鼠组收缩压及心率的影响。②分别用比色法测血清一氧化氮水平、放射免疫法测血浆内皮素、血管紧张素Ⅱ水平。 结果：实验组注射肝细胞生长因子5μg/g血压下降不明显，注射10ug／kg约5min后血压开始下降，30min降至最低，1h后血压开始逐渐回升，5h后血压基本回到原先水平。注射20ug／kg达最大降压幅度，收缩压下降达40～50mmHg，再增加剂量最大降压幅度及持续时间不变。整过程心率无明显变化。两个对照组血压无明显变化。实验组较自发性高血压大鼠组内皮素、血管紧张素Ⅱ含量下降，一氧化氮含量上升（P〈0．05）。 结论：从静脉给予外源性肝细胞生长因子能快速降低自发性高血压大鼠组的血压，在一定剂量范围内，呈剂量-效应与时间-效应关系。肝细胞生长因子系统、血管内皮系统、肾素-血管紧张素系统可能共同参与血压的调节。     

Exaggerated natriuresis in the conscious spontaneously hypertensive rat.

In response to an acute saline load, many patients with essential hypertension exhibit an exaggerated natriuresis relative to normotensive controls. In the present study, the urinary responses of conscious,Okamoto-strain, spontaneously hypertensive rats (SHR), and Wistar-Kyoto strain normotensive rats (NTR) to an acute saline load were evaluated to determine if a similar exaggerated natruiresis exists in this form of hypertension. Twelve rats of each strain per group (12 weeks of age) were housed in metabolism cages for 1 week. Systolic blood pressures (tail cuff) were significantly different (206+/- 9 mm. Hg in SHR and 135 +/- 3 mm. Hg in NTR). After a 4-hour control urine collection, 6 ml. of 0.9 per cent sodium chloride were given by gavage. Urine was collected again for 2 hours. Control urinary excretions of sodium, potassium, and creatinine in SHR and NTR were 11.2 +/- 4.8 muEq per hour, 50.1 +/- 7.6 muEq per hour, and 39.9 +/- 5.5 mg. per hour in SHR, and 13.8 +/- 2.4 muEq per hour, 34.9 +/- 5.5 muEq per hour, and 37.5 +/- 7.1 mg. per hour in NTR, respectively. The respective control values for sodium, potassium, and creatinine excretion in the two groups were not significantly different. Following the saline load, sodium and creatinine excretion rates were significantly elevated in both groups of rats. However, the increase in sodium excretion in SHR (60.8 +/- 7.2 MUEq per hour) was more than double and significantly different from that of the NTR (26.6 +/- 3.7 muEq per hour). In contrast, the increments in creatinine excretion in the two groups of rats were not significantly different from each other. In the NTS, urinary potassium excretion was significantly elevated (59.0 +/- 7.9 muEq per hour) whereas in SHR it was not significantly altered (12.0 +/- 8.8 muEq per hour). The change in urinary creatinine excretion as an index of change in glomerular filtration rate suggests that the greater increase in sodium excretion by the SHR was the result of decreased fractional reabsorption of sodium and not the result of a greater increase in glomerular filtration rate. The exaggerated natriuretic response to salt loading in SHR resembles that in hypertensive man except that in SHR, a simultaneous kaliuretic response is absent.     

黄芪对自发性高血压大鼠血压的急性效应

目的　观察黄芪对自发性高血压大鼠 (SpontaneouslyHypertensiveRats,SHR)血压的急性影响。方法　腹腔给予不同剂量的黄芪后 ,用间接测压法测定SHR血压。再分别连续给予不同剂量的黄芪 ,8周后 ,用直接法测定静脉给予黄芪对SHR血压的影响。结果　 1、SHR腹腔注射不同剂量黄芪在观察的各时间点 (5分、15分、30分、6 0分、12 0分 )并不引起血压的急性变化 (P >0 .0 5 )。 2、黄芪长期腹腔注射可以控制SHR血压的升高 (P <0 .0 1)。 3、急性静脉给药可以引起SHR血压短时间内明显下降 ,并且呈剂量相关效应 (P <0 .0 5或P <0 .0 1)。结论　黄芪急性腹腔给药不影响SHR血压 ,但长期腹腔给药可以控制SHR血压的升高。急性静脉给药可以引起短时间内明显的血压下降。     

Cosinor analysis of changes in circadian blood pressure rhythm with aging in spontaneously hypertensive rats

Evolution of circadian rhythm of blood pressure with age in male spontaneously hypertensive rats (SHR) was compared with that in male Wistar Kyoto rats (WKY). Three different age groups (5-6 week old, 19-22 week old, 29-31 week old) were provided for each strain. Chronogram and cosinor method were used for time series analyses. In all age groups of WKY, a diurnal fall and a nocturnal rise in blood pressure (BP) as well as in heart rate (HR) were observed. There was no significant difference in acrophase between BP and HR in each age group of WKY. Regarding SHR, however, each age group demonstrated a different relation between circadian BP rhythm and HR rhythm. In 5-6 week old SHR, a difference in acrophase between BP and HR (about 6.9 hr, p less than 0.1) was observed, which became more conspicuous with the increase in age, eventually presenting an inverted relation between BP and HR in 19-22 week old SHR. The relation between circadian BP rhythm and circadian HR rhythm in 29-31 week old SHR was almost identical with that in 19-22 week old SHR. In other words, a phase lag of acrophase of BP from that of HR already observed in young SHR increased with aging. The results indicate that parasympathetic periodicity remained unchanged even in SHR since circadian HR rhythm was similar in all groups, while the periodicity of sympathetic neural tone relating to the regulation of circadian BP rhythm seems to be disturbed. The mechanism responsible for development and maintenance of high BP in SHR may be linked to a disturbance in the sympathetic mechanism which regulates BP periodicity.     

运动对高血压大鼠血压和内皮素的影响

目的：观察原发性高血压大鼠运动后血压、体质量以及血清内皮素的变化。方法：实验于2003-07/09在扬州大学实验动物中心完成。采用18只高血压大鼠作为实验动物，按实验需要将动物分为运动组（10只）和安静组（8只）。运动组经过10周的60min/d的训练，5d/周，与安静组一起测量其血压、体质量；取静脉血，用放射免疫法测定内皮素。结果：实验进行至第5周运动组死亡1只大鼠。①血压：运动前两组大鼠血压无显著差异，经过4，10周运动后运动组大鼠与安静组相比血压明显降低[（174．1&;#177;1.4），（185．0&;#177;1．4）mm Hg；（166．6&;#177;1．1），（193．9&;#177;1．8）mm Hg，P〈0．01]。②体质量：两组动物在生长过程中体质量均逐渐增高，但运动组增长的趋势低于安静组，经10周运动后运动组的体质量明显低于安静组[（344．60&;#177;2．57），（362．00&;#177;5．26）g，P〈0．05]。③内皮素：经过10周的游泳训练后，运动组内皮素明显低于安静组[144．75&;#177;4．45），（68．36&;#177;5．93）ng/L，P〈0.01]。结论：运动对高血压大鼠的体质量增长有抑制作用，且高血压大鼠经过游泳训练后其血内皮素水平下降，而血压也随之下降，提示运动对高血压大鼠的降压部分是通过影响内皮素的产生和释放来实现的。     

运动对高血压大鼠血压和内皮素的影响

目的押观察原发性高血压大鼠运动后血压、体质量以及血清内皮素的变化。方法押实验于2003-07/09在扬州大学实验动物中心完成。采用18只高血压大鼠作为实验动物,按实验需要将动物分为运动组穴10只雪和安静组穴8只雪。运动组经过10周的60min/d的训练熏5d/周,与安静组一起测量其血压、体质量;取静脉血,用放射免疫法测定内皮素。结果押实验进行至第5周运动组死亡1只大鼠。①血压:运动前两组大鼠血压无显著差异熏经过4,10周运动后运动组大鼠与安静组相比血压明显降低眼(174.1±1.4),(185.0±1.4)mmHg;(166.6±1.1),(193.9±1.8)mmHg,P<0.01演。②体质量:两组动物在生长过程中体质量均逐渐增高,但运动组增长的趋势低于安静组,经10周运动后运动组的体质量明显低于安静组眼(344.60±2.57),(362.00±5.26)g,P<0.05演。③内皮素:经过10周的游泳训练后,运动组内皮素明显低于安静组眼穴44.75±4.45雪,穴68.36±5.93雪ng/L,P<0.01演。结论押运动对高血压大鼠的体质量增长有抑制作用,且高血压大鼠经过游泳训练后其血内皮素水平下降,而血压也随之下降,提示运动对高血压大鼠的降压部分是通过影响内皮素的产生和释放来实现的。     

低强度游泳运动对自发性高血压大鼠C反应蛋白的影响

目的研究低强度游泳运动对自发性高血压大鼠(SHR)C反应蛋白(CRP)的影响。方法24只8周龄SHR大鼠随机分为对照组及运动组,运动组进行游泳运动1 h/d,5 d/w,共10 w。每周测量大鼠尾动脉压,实验结束时检测CRP水平。结果10 w低强度游泳运动明显降低SHR大鼠血压及CRP水平。结论低强度游泳运动有助于降低高血压患者的血压并减少心血管系统并发症。     

Effect of acute and chronic treatment of tin on blood pressure in spontaneously hypertensive rats.

Cytochrome P450-dependent metabolites of arachidonic acid (AA) are increased in the kidneys of spontaneously hypertensive rats (SHR) as compared to control rats (WKY) in the period of rapid elevation of blood pressure (BP) from 5 to 13 weeks. We treated rats with stannous chloride (SnCl2) (10 mg/100 g body weight/day for 4 days) to decrease selectively renal cytochrome P450 content through increasing renal heme oxygenase activity. A decrease in renal cytochrome P450-dependent AA metabolites was associated with decreased BP and increased urinary Na+ excretion in 7- but not in 20-week-old SHR rats. Chronic treatment with SnCl2 (10 mg/100 g body weight twice a week) from 5 to 20 weeks prevented the elevation of BP in SHR rats. Further, the antihypertensive effects of tin persisted for 7 weeks beyond its discontinuation. BP in WKY rats was unaffected by tin. Both the acute and chronic treatment with tin are the first studies to demonstrate amelioration of hypertension in SHR by an intervention which is targeted at a single enzyme system.     

Blockade of endogenous anterior hypothalamic atrial natriuretic peptide with monoclonal antibody lowers blood pressure in spontaneously hypertensive rats.

We have previously shown that the atrial natriuretic peptide (ANP) content of the anterior hypothalamic region of NaCl-sensitive spontaneously hypertensive rats (SHR-S) is higher than that of Wistar-Kyoto (WKY) rats. ANP has been shown to inhibit neuronal norepinephrine release and to reduce the excitability of hypothalamic neurons. This study tested the hypothesis that blockade of endogenous ANP in the anterior hypothalamus by local microinjection of a monoclonal antibody to ANP (MAb KY-ANP-II) lowers blood pressure in SHR-S. Purified MAb KY-ANP-II (0.055 and 0.55 micrograms) or control mouse IgG in 200 nl saline was microinjected into the anterior hypothalamic area (AHA) of conscious SHR-S and control WKY rats. As a further control, Mab KY-ANP-II (0.55 microgram) was microinjected into the posterior hypothalamic area (PHA) of SHR-S. Anterior hypothalamic microinjection of MAb KY-ANP-II caused significant dose-related decreases in mean arterial pressure (MAP) and heart rate (HR) in SHR-S but not in WKY rats. Control injections of equal volumes of IgG had no effect on MAP or HR. Microinjection of Mab KY-ANP-II into PHA produced no significant alteration in MAP or HR in SHR-S. These data provide the first demonstration that endogenous ANP in a region of brain known to influence cardiovascular function mediates BP and HR control in the rat. These findings suggest that the increased endogenous ANP in the anterior hypothalamus of SHR-S may be involved in the central regulation of BP in the model.     

A widespread abnormality of renin gene expression in the spontaneously hypertensive rat: modulation in some tissues with the development of hypertension

1. Renin messenger RNA (mRNA) levels were compared in the kidneys, livers, brains, adrenals, aortae and hearts of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at 5 and 12 weeks of age using a ribonuclease-protection technique. 2. Relative levels of renin mRNA were increased in the kidney, liver, brain, adrenal and heart of the young SHR compared with the WKY. In the aorta, levels were similar in the two strains at 5 weeks. 3. In 12-week-old animals, while increased levels persisted in the liver, brain and adrenal of the SHR, the level in the kidney was now the same in the two strains and the levels in the heart and aorta were lower in the SHR compared with the WKY. 4. Renin mRNA levels in the kidneys of SHR and WKY were also compared by Northern blotting and confirmed the observations made with the ribonuclease-protection technique. 5. The findings indicate a widespread abnormality of renin gene expression in the SHR which is modulated in some tissues by the development of hypertension. 6. While the mechanism(s) for the abnormality remains to be determined, the increased renin mRNA levels in the SHR in several tissues concerned with blood pressure regulation suggests an important role for the renin-angiotensin system in the development and maintenance of hypertension. 7. However, the finding of increased renin mRNA in the liver also suggests abnormalities in other, as yet unknown, functions of the renin-angiotensin system in the SHR.     

Renal sensitivity to endothelium-derived-relaxing-factor-mediated vasodilatation in the spontaneously hypertensive rat.

1. The sensitivity of the kidney to endothelium-derived-relaxing-factor-mediated vasodilatation has been investigated in the spontaneously hypertensive rat and the Wistar-Kyoto normotensive rat using an isolated perfused rat kidney model. 2. No difference in the slope, ED50 or maximum of the concentration-response curves for the endothelial-dependent vasodilators A23187, a calcium ionophore, and acetylcholine could be demonstrated between kidneys obtained from the spontaneously hypertensive and the Wistar-Kyoto normotensive rats. 3. No difference in the slope or the ED50 of the concentration-response curve for the endothelial-independent vasodilators, atrial natriuretic factor and sodium nitroprusside, could be demonstrated between kidneys obtained from the spontaneously hypertensive and the Wistar-Kyoto normotensive rats. However, in the spontaneously hypertensive rats, the maximum vasodilator response to atrial natriuretic factor, but not to sodium nitroprusside, was increased. 4. The perfused kidney from the spontaneously hypertensive rat also showed an increase in the maximum but not in the slope or ED50 of the concentration-response curve for vasoconstriction induced by the alpha 1-adrenoceptor agonist methoxamine. 5. The involvement of endothelium-derived relaxing factor in mediating the renal vasodilator response to A23187 and acetylcholine was confirmed in experiments performed in perfused kidneys obtained from normotensive Wistar rats. 6. It is concluded that the sensitivity of the kidney to endothelium-derived-relaxing-factor-mediated vasodilatation is not modified in the spontaneously hypertensive rat. This does not, however, exclude a role for the synthesis of endothelium-derived relaxing factor in the maintenance of blood pressure in the spontaneously hypertensive rat.