Involvement of AT(1) angiotensin receptors in the vasomodulatory effect of des-aspartate-angiotensin I in the rat renal vasculature

Angiotensin II is known to act primarily on the angiotensin AT(1) receptors to mediate its physiological and pathological actions. Des-aspartate-angiotensin I (DAA-I) is a bioactive angiotensin peptide and have been shown to have contrasting vascular actions to angiotensin II. Previous work in this laboratory has demonstrated an overwhelming vasodepressor modulation on angiotensin II-induced vasoconstriction by DAA-I. The present study investigated the involvement of the AT(1) receptor in the actions of DAA-I on angiotensin II-induced vascular actions in the renal vasculature of normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and streptozotocin (STZ)-induced diabetic rats. The findings revealed that the angiotensin receptor in rat kidney homogenate was mainly of the AT(1) subtype. The AT(1) receptor density was significantly higher in the kidney of the SHR. The increase in AT(1) receptor density was also confirmed by RT-PCR and Western blot analysis. In contrast, AT(1) receptor density was significantly reduced in the kidney of the streptozotocin-induced diabetic rat. Perfusion with 10(-9)M DAA-I reduced the AT(1) receptor density in the kidneys of WKY and SHR rats suggesting that the previously observed vasodepressor modulation of the nonapeptide could be due to down-regulation or internalization of AT(1) receptors. RT-PCR and Western blot analysis showed no significant changes in the content of AT(1) receptor mRNA and protein. This supports the suggestion that DAA-I causes internalization of AT(1) receptors. In the streptozotocin-induced diabetic rat, no significant changes in renal AT(1) receptor density and expression were seen when its kidneys were similarly perfused with DAA-I.     

Histochemical characterization of silver-induced metallothionein in rat kidney

Histochemical characterizations of Ag-induced metallothionein (MT) in the kidney of the rat have been reported. Ag, Cu and Zn contents increased in kidney and liver after Ag injection. In particular, the Cu content in kidneys increased dramatically after three injections of Ag. Sephadex G-75 elution profiles of the renal cytosol of rats injected with Ag revealed that the accumulated Cu in the kidney was bound to MT as were Ag and Zn. In addition, localization of Cu- and Ag-MT in the kidney was studied using autofluorescent signals, which are dependent on Cu- or Ag-thiol clusters, and immunohistochemistry. Although the MT induced by Ag was predominantly observed in the cortex of the kidney, some MT signals were also detected in the outer stripe of the outer medulla, as well as in the kidneys of LEC rats, an animal model of Wilson disease (a hereditary disorder of Cu metabolism). In these LEC rats, the Cu-MT also accumulated in the outer stripe of the outer medulla of the kidney. From these results, one possibility could explain that the Cu-MT detected in the outer stripe of the outer medulla in the kidney of Ag-injected rat was associated with the Cu transporter affected by Ag.     

Effects of high salt intake on brain AT1 receptor densities in Dahl rats

To assess effects of dietary salt on brain AT1 receptor densities, 4-wk-old Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats were fed a regular (101 mumol Na/g) or high (1,370 mumol Na/g)-salt diet for 1, 2, or 4 wk. AT1 receptors were assessed by quantitative in vitro autoradiography. AT1 receptor densities did not differ significantly between strains on the regular salt diet. The high-salt diet for 1 or 2 wk increased AT1 receptor binding by 21-64% in the Dahl S rats in the subfornical organ, median preoptic nucleus, paraventricular nucleus, and suprachiasmatic nucleus. No changes were noted in the Dahl R rats. After 4 wk on a high-salt diet, increases in AT1 receptor binding persisted in Dahl S rats but were now also noted in the paraventricular nucleus, median preoptic nucleus, and suprachiasmatic nucleus of Dahl R rats. At 4 wk on the diet, intracerebroventricular captopril caused clear decreases in blood pressure only in the Dahl S on the high-salt diet but caused largely similar relative increases in brain AT1 receptor densities in Dahl S and R on the high-salt diet versus regular salt diet. These data demonstrate that high salt intake rapidly (within 1 wk) increases AT1 receptor densities in specific brain nuclei in Dahl S and later (by 4 wk) also in Dahl R rats. Because the brain renin-angiotensin system only contributes to salt-induced hypertension in Dahl S rats, further studies are needed to determine which of the salt-induced increases in brain AT1 receptor densities contribute to the hypertension and which to other aspects of body homeostasis.     

α1-Adrenergic Receptors in Neuronal Cultures from Rat Brain: Increased Expression in the Spontaneously Hypertensive Rat

Neuronal cells in primary culture from 1-day-old brains of normotensive, Wistar-Kyoto strain (WKY) and spontaneously hypertensive (SH) rats have been utilized to study the expression of alpha 1-adrenergic receptors. Binding of a selective alpha 1 antagonist, [125I]2-[beta-(4-hydroxy-3-iodophenyl)-ethylaminomethyl]-tetralone ([125I]HEAT) to neuronal membranes prepared from primary brain cultures of WKY and SH rats was 75-80% specific, rapid, and time-dependent although the binding was 1.5-2 times higher in neuronal membranes from SH rat brain cultures. Kinetic analysis of the association and dissociation data demonstrated no significant differences between rat strains. Competition-inhibition experiments provided IC50 values for various antagonists and agonists in the following order: prazosin less than phentolamine less than yohimbine less than phenylephrine less than norepinephrine less than propranolol, suggesting that [125I]HEAT bound selectively to alpha 1-adrenergic receptors. Scatchard analysis of the binding data provided straight lines for both strains of rats, indicating the presence of a homogeneous population of binding sites. It also showed that the increase in the binding in neuronal cells from SH rat brains over those from normotensive WKY controls was a result of an increase in the number of alpha 1-adrenergic receptors. Incubation of neuronal cultures from both strains of rats with phenylephrine, an alpha 1-adrenergic agonist, caused a time- and dose-dependent decrease in the binding of [125I]HEAT. This decrease was due to a decrease in the number of alpha 1-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Localization of the induced metallothionein and DNA damage in rat kidney after gold injection.

To clarify the relationships between DNA damage and Cu-MT and between DNA damage and Cu in kidneys of rats injected with Au, we examined the histochemical localization of DNA damage, metallothionein (MT), and the accumulated Cu in the kidneys of rats injected with Au, Cu, or Cu-MT. The immunoreactivity of MT was observed predominantly in the outer stripe of the outer medulla and the inner cortex of the Au-injected rat, and the signals of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) were observed in the cortex. Cu detected by Timm's method was mainly distributed in the cortex of the Au-injected rat. These results indicated that DNA damage could be caused by free Cu in the cortex but not by the Cu bound to MT in the outer stripe of the outer medulla. This consideration was supported by the data from rats injected with Cu and Cu-MT. Furthermore, we determined the Cu contents in three fractions (cytosol, organelle, and precipitate-containing nuclei) of the kidneys. Interestingly, most of the Cu content in the kidney of the rat injected with Au or Cu-MT was detected in the cytosol, whereas most of the Cu content in the kidney of the rat injected with Cu was detected in the nuclei-containing precipitate. These findings suggest that the DNA damage in the kidneys of rats injected with Au may be associated with Cu-binding proteins but not with Cu-MT.     

Regulation of angiotensin II receptors in the medullary thick ascending limb

Angiotensin II (Ang II) is an important regulator of the function of medullary thick ascending limb of loop of Henle (MTAL). Recent studies showed that changes in Ang II receptor expression occur and underlie changes in the function of proximal tubules during altered sodium intake. The present experiment was designed to determine (1) whether expression of the type 1 Ang II (AT1) receptor in the MTAL is regulated by altered sodium intake, and (2) the specific pathway(s) mediating sodium-induced AT1 expression in the MTAL. Wistar rats were fed a normal sodium (0.5%, NS), low sodium (0.07%, LS), or high sodium (4%, HS) diet for 2 weeks. Northern blot analysis and radioligand binding showed that in rats fed a normal sodium diet the rank of order for both AT1 mRNA expression and receptor density was outer medulla > cortex > inner medulla. Sodium restriction significantly increased both AT1 mRNA expression and receptor density in the outer medulla. In contrast, neither AT1 mRNA expression nor receptor density in the outer medulla was altered by sodium loading. Losartan treatment (3 mg/kg/per day by oral gavage for 2 weeks) prevented low sodium-induced upregulation of the AT1 receptor in the outer medulla, but it had no effect on AT1 expression in the outer medulla of rats fed a normal sodium diet. Highly purified suspensions of MTAL were isolated from rats fed a normal or low sodium diet. Low sodium intake significantly increased AT1 mRNA level by 184% and AT1 receptor density by 58% in MTALs. Primary cultures of MTAL cells were treated with PBS, Ang II (10^-8 M), and Ang II + 17 octadecynoic (17 ODYA, 10 M). Ang II caused about 2-fold increase in AT1 mRNA levels, and this increase was diminished by about 30% by the addition of 17 ODYA. We conclude that (1) sodium restriction but not sodium loading increases AT1 receptor expression in the MTAL, (2) low sodium-induced upregulation of the AT1 receptor in the MTAL is Ang II-dependent, and (3) Ang II-induced upregulation of the AT1 receptor in the MTAL is mediated, at least in part, by cytochrome P450 pathways.     

Pathophysiological roles of vascular 11beta-hydroxysteroid dehydrogenase and aldosterone

Mineralocorticoid receptor (MR) binding is tightly regulated by the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSDII) which selectively metabolizes glucocorticoids to inactive metabolites, thus allowing for MR activation by aldosterone. To examine whether this enzyme is involved in the pathophysiology of salt-sensitive hypertension, 11β-HSDII activity and messenger RNA (mRNA) levels were determined in blood vessels of Dahl Iwai salt-sensitive (DS) and salt-resistant (DR) rats. Decreased 11β-HSDII activity and mRNA levels in mesenteric arteries were observed in 8-week-old DS rats on a high-salt diet, indicating that 11β-HSDII may play a significant role in salt sensitivity and hypertension. It has been suggested that mineralocorticoids act on blood vessels, leading to increased vasoreactivity and peripheral resistance. We present direct evidence that blood vessels are aldosteronogenic. The production of aldosterone in blood vessels was compared between stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. Vascular aldosterone and CYP11B2 mRNA levels were significantly increased in 2-week-old SHRSP versus WKY rats. However, the vascular aldosterone levels in 4- and 9-week-old SHRSP and WKY rats were similar. High sodium intake further increased both blood pressure and vascular aldosterone synthesis in the SHRSPs. Both the local renin–angiotensin–aldosterone system (RAAS) and the vascular 11β-HSDII level are critically important in the pathophysiology of cardiovascular disorders.     

Sodium homeostasis in transplanted rats with a spontaneously hypertensive rat kidney

Recipients of a kidney from spontaneously hypertensive rats (SHR) but not from normotensive Wistar-Kyoto rats (WKY) develop posttransplantation hypertension. To investigate whether renal sodium retention precedes the development of posttransplantation hypertension in recipients of an SHR kidney on a standard sodium diet (0.6% NaCl), we transplanted SHR and WKY kidneys to SHR x WKY F1 hybrids, measured daily sodium balances during the first 12 days after removal of both native kidneys, and recorded mean arterial pressure (MAP) after 8 wk. Recipients of an SHR kidney (n = 12) retained more sodium than recipients of a WKY kidney (n = 12) (7.3 +/- 10 vs. 4.0 +/- 0.7 mmol, P < 0.05). MAP was 144 +/- 6 mmHg in recipients of an SHR kidney and 106 +/- 5 mmHg in recipients of a WKY kidney (P < 0.01). Modest sodium restriction (0.2% NaCl) in a further group of recipients of an SHR kidney (n = 10) did not prevent posttransplantation hypertension (MAP, 142 +/- 4 mmHg). Urinary endothelin and urodilatin excretion rates were similar in recipients of an SHR and a WKY kidney. Transient excess sodium retention after renal transplantation may contribute to posttransplantation hypertension in recipients of an SHR kidney.     

Altered expression of phospholipase D1 in spontaneously hypertensive rats.

To clarify the involvement of phospholipase D (PLD) in the mechanism underlying genetically-induced hypertension, we investigated the activity and expression levels of PLD in tissues taken from spontaneously hypertensive rats (SHR), and their normotensive controls, Wistar-Kyoto rats (WKY). The ADP-ribosylation factor 3 (ARF3)-dependent PLD activity and protein levels of PLD1 from SHR increased significantly in the brain and liver, but not in the heart and kidney, compared to those of WKY. The activity and expression of PLD were the same between the homogenated whole kidneys of the two strains; however, there were topographical differences in the expression and activity of PLD between the kidneys of the two strains. The activity and expression level of PLD gradually increased from the cortex to the inner medulla of WKY. The enzyme activity, and amount of PLD in the inner stripe of the outer medulla and in the inner medulla, was significantly lower in SHR than in WKY. Taken together, these results suggest that the distinctly distributed patterns of PLD in the kidney may be associated with differential signal transduction pathways that are involved in hypertension in conjunction with an increase of PLD activity in the brain and liver.     

Increased expression of urotensin II-related peptide and its receptor in kidney with hypertension or renal failure

Urotensin II-related peptide (URP) is a novel vasoactive peptide that shares urotensin II receptor (UT) with urotensin II. In order to clarify possible changes of URP expression in hypertension and chronic renal failure (CRF), the expressions of URP and UT were studied by quantitative RT-PCR and immunohistochemistry in kidneys obtained from spontaneous hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and WKY with CRF due to 5/6 nephrectomy. Expression levels of URP mRNA and UT mRNA were significantly higher in the kidneys obtained from SHR compared with age-matched WKY (at 5-16 and 16 weeks old, respectively). A dissection study of the kidney into three portions (inner medulla, outer medulla and cortex) showed that the expression levels of URP mRNA and UT mRNA were highest in the inner medulla and the outer medulla, respectively, in both SHR and WKY. The expression levels of URP and UT mRNAs were greatly elevated in the remnant kidneys of CRF rats at day 56 after nephrectomy, compared with sham-operated rats (about 6.5- and 11.9-fold, respectively). Immunohistochemistry showed that URP immunostaining was found mainly in the renal tubules, vascular smooth muscle cells and vascular endothelial cells. UT immunoreactivity was localized in the renal tubules and vascular endothelial cells. These findings suggest that the expressions of URP and UT mRNAs in the kidney are enhanced in hypertension and CRF, and that URP and its receptor have important pathophysiological roles in these diseases.     

Chronic effects of angiotensin-converting enzyme inhibition on kinin receptor binding sites in the rat spinal cord

With the use of in vitro receptor autoradiography, this study aims at determining whether the higher level of kinin B(2) receptor density in the spinal cord of the spontaneously hypertensive rat (SHR) is secondary to arterial hypertension and whether chronic treatment with angiotensin I-converting enzyme inhibitors (ACEI) can regulate neuronal B(1) and B(2) receptors. SHR received, from the age of 4 wk, one of the two ACEI (lisinopril or zofenopril, 10 mg x kg(-1) x day(-1)) or for comparison, the selective AT(1) antagonist (losartan, 20 mg x kg(-1) x day(-1)) in their drinking water for a period of 4, 12, and 20 wk. Age-matched untreated SHR and Wistar-Kyoto rats (WKY) were used as controls. B(2) receptor binding sites in most laminae were higher in SHR than in WKY from the age of 8 to 24 wk. Whereas B(1) receptor binding sites were significantly present in young SHR and WKY, they were barely detectable in adult rats. ACEI (16 and 24 wk) and AT(1) antagonist (24 wk) enhanced the number of B(2) without changing B(1) receptor binding sites. However, at 8 wk the three treatments significantly increased B(1) and decreased B(2) receptors in lamina I. It is concluded that 1) the higher density of B(2) receptors in the spinal cord of SHR is not due to hypertension, 2) kinin receptors are regulated differently by ACEI in neuronal and vascular tissues, and 3) aging may have a profound impact on levels of B(1) and B(2) receptors in the rat spinal cord.     

Dietary sodium regulation of blood pressure and renal alpha 1- and alpha 2-receptors in WKY and SH rats

We studied the effect of high (8%) versus normal (0.6%) sodium diet on renal α₁ and α₂-adrenergic receptors and on blood pressure in Okamoto-Aoki spontaneously hypertensive (SH) and Wistar Kyoto (WKY) “normotensive” rats. SH rats had higher renal α₁ (p<.05) and ga₂-receptor densities (p<.05) and blood pressure (p<.001) than WKY rats on normal salt diets. High salt (8% NaCl) diet increased the already elevated α₂-receptor density (p<.001) and blood pressure (p<.005) even higher in the SH rats after two and after five weeks. After two weeks of high salt diet α₂-receptor density had increased by 27% (p<.01) in WKY rats and the blood pressure had increased (p>.01). Ingestion of the high salt diet for 5 weeks increased blood pressure from 130 mmHg to 174 mmHg (p<.001) and α₂-receptor density from 255 and 375 fMo1/mg protein (p<.001) in the WKY rats. We conclude: 1) Renal α₁ and α₂-receptor density is higher in the SH than in WKY rats 2) The dietary sodium-induced increase in α₂-receptor density in WKY rats and anedates most of the elevation of blood pressure 3) The increase in blood pressure is directly related to the increase in renal α₂-receptor density in SH and WKY rats. Thus, the increment in renal α₂-receptor density appears to be a genetic marker of hypertension and could be related to a basic hypertensive mechanism.     

正常大鼠植入高血压大鼠肾脏后 动脉血压的变化

本实验对12周龄的自发性高血压大鼠(spontaneously hypertensive rat,SHR)及其对照组Wistar Kyoto (WKY)大鼠进行了肾脏移植的研究, 并观察受肾移植大鼠动脉血压的变化以及免疫抑制剂对动脉血压的影响。 用尾套法对接受同窝另一同胞WKY大鼠肾脏移植且存活5周的6只WKY大鼠(A组)及接受SHR肾脏移植且存活5周的6只WKY大鼠(B组)的尾动脉收缩压进行检测, 移植前A、 B两组受肾移植大鼠的尾动脉收缩压分别为18.0±0.93 和18.3±0.68 kPa,无统计学显著差异(P>0.05); 移植后3、 4、 5周时, B组大鼠的尾动脉收缩压显著高于A组大鼠, 移植后5周时, A, B两组大鼠的收缩压分别为19.0±0.71 和23.0±0.69 kPa (P<0.001); 所用剂量的免疫抑制剂CsA对双侧肾脏完整以及右侧肾脏切除的SHR、 WKY大鼠的动脉血压无显著影响。 以上结果表明, SHR的肾脏在高血压的形成中可能起重要作用。     

正常大鼠植入高血压大鼠肾脏后动脉血压的变化

本实验对12周龄的自发性高血压大鼠(spontaneouslyhypertensiverat,SHR)及其对照组WistarKyoto(WKY)大鼠进行了肾脏移植的研究,并观察受肾移植大鼠动脉血压的变化以及免疫抑制剂对动脉血压的影响。用尾套法对接受同窝另一同胞WKY大鼠肾脏移植且存活5周的6只WKY大鼠(A组)及接受SHR肾脏移植且存活5周的6只WKY大鼠(B组)的尾动脉收缩压进行检测,移植前A、B两组受肾移植大鼠的尾动脉收缩压分别为180±093和183±068kPa,无统计学显著差异(P>005);移植后3、4、5周时,B组大鼠的尾动脉收缩压显著高于A组大鼠,移植后5周时,A,B两组大鼠的收缩压分别为190±071和230±069kPa(P<0001);所用剂量的免疫抑制剂CsA对双侧肾脏完整以及右侧肾脏切除的SHR、WKY大鼠的动脉血压无显著影响。以上结果表明,SHR的肾脏在高血压的形成中可能起重要作用     

Androgens drive divergent responses to salt stress in male versus female rat kidneys

Dahl-Iwai (DI) salt-sensitive rats were studied using microarrays to identify sex-specific differences in the kidney, both basal differences and differences in responses to a high-salt diet. In DI rat kidneys, gene expression profiles demonstrated inflammatory and fibrotic responses selectively in females. Gonadectomy of DI rats abrogated sex differences in gene expression. Gonadectomized female and gonadectomized male DI rats both responded to high salt with the same spectrum of gene expression changes as intact female DI rats. Androgens dominated the sex-selective responses to salt. Several androgen-responsive genes with roles potentiating the differential responses to salt were identified, including increased male expression of angiotensin-vasopressin receptor and prolactin receptor, decreased 5 alpha-reductase, and mixed increases and decreases in expression of Cyp4a genes that can produce eicosanoid hormones. These sex differences potentiate sodium retention by males and increase kidney function during gestation in females.     

Differential changes in atrial natriuretic peptide and vasopressin receptor bindings in kidney of spontaneously hypertensive rat

To elucidate the role of atrial natriuretic peptide (ANP) and vasopressin (VP) in a hypertensive state, ANP and VP receptor bindings in spontaneously hypertensive rat (SHR) kidney were analyzed using the radiolabeled receptor assay (RRA) technique. Systolic blood pressure of SHR aged 12 weeks was statistically higher than that of age-matched Wistar Kyoto (WKY) rats. Maximum binding capacity (Bmax) of [125I]-ANP binding to the SHR kidney membrane preparations was statistically lower than that of WKY rats, but dissociation constant (Kd) was not significantly different. On the other hand, Bmax of [3H]-VP binding to the SHR kidney membrane preparations was statistically higher than that of WKY rats, but Kd were similar. Since the physiological action of ANP is natriuresis and VP is the most important antidiuretic hormone in mammalia, these opposite changes of ANP and VP receptor bindings in SHR kidney suggested that these peptides may play an important role in the pathophysiology of the hypertensive state, although it has not been confirmed as yet.     

Identification and characterization of binding sites for human urotensin-II in Sprague-Dawley rat renal medulla using quantitative receptor autoradiography

Urotensin-II (U-II), a ligand for the G-protein-coupled receptor UT, has been characterized as the most potent mammalian vasoconstrictor identified to date. Although circulating levels of U-II are altered in lower species (e.g., fish) upon exposure to hypo-osmotic stress, little is known about the actions of this cyclic undecapeptide within the kidney, an organ that plays a pivotal role in the control of cardiovascular homeostasis, influencing both cardiac preload (plasma volume) and after load (peripheral resistance). The present study reports the identification of specific, high affinity [125I]hU-II binding sites in Sprague-Dawley rat kidney outer medulla by autoradiography and also through membrane radioligand binding (Kd 1.9 +/- 0.9 nM and Bmax 408 +/- 47 amol mm(-2) and Kd 1.4 +/- 0.3 nM and Bmax 51.3 +/- 7.8 fmol mg(-1) protein, respectively). Differences were observed in the binding characteristics within rat strains. Compared to the Sprague-Dawley, Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rat kidney outer medulla displayed low density < 20 fmol mg(-1) protein and low affinity (> 1 microM) [125I]hU-II binding sites. Thus, the relative contribution of specific U-II binding sites to the physiological actions of U-II in the control of cardiorenal homeostasis is worthy of further investigation.     

不同年龄白发性高血压大鼠肾脏AT1R和AT2R的表达

目的本研究观察不同月龄自发性高血压大鼠（SHR）肾脏ALR和ALR表达,初步探讨AT1R和AT2R在高血压发生、发展过程中的可能作用。方法1月龄组（S1）、2月龄组（S2）、3月龄组（S3）、6月龄组（S6）和9月龄组（墨）雄性SHR共5组,每组各6只,各组均有相应月龄匹配的Wistar-Kyoto大鼠（WKY）作对照。采用RBP-I型大鼠血压心率测定仪测量大鼠尾动脉收缩压（SBP）;放免法测定血浆血管紧张素Ⅱ（AngⅡ）;免疫组化染色结合计算机图像分析方法测定肾脏AT1R和ALR表达水平。结果（1）SHR SBP随着月龄的增加而上升,S6后趋于稳定。（2）1个月后SHR血浆AngⅡ浓度均高于S1（P〈0.05）,而S2、S3、S6和S9之间无明显差别（P〉0.05）;1个月后SHR血浆AngⅡ浓度均高于相应配对的WKY组（P〈0.05）;而WKY各月龄组均无明显差别（P〉0.05）。（3）SHR肾脏AT1R随着月份的增加而增加（P〈0.05）,且高于相应配对的WKY组（P〈0.05）。SHR肾脏ABR随着月份的增加而降低,S6明显降低（P〈0.05）,S6和S9比较无明显差别（P〉0.05）;且均低于相应配对的WKY组（P〈0.05）。WKY各月龄组AT1R和AT2R无明显差别（P〉0.05）。结论SHR肾脏AT1R表达水平比WKY高,并随着年龄的增加而递增;AT2R表达水平比WKY低,并随着年龄的增加而降低。