11β-HYDROXYSTEROID DEHYDROGENASE ACTIVITY IN MESENTERIC ARTERIES OF SPONTANEOUSLY HYPERTENSIVE RATS

1. 11β-Hydroxysteroid dehydrogenase (11-HSD) activity in mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was determined and expressed as the percentage conversion of [³H]-corticosterone to [³H]-11-dehydrocorticosterone. 2. 11-HSD activity was significantly decreased in mesenteric arteries of both 4 and 9 week old SHR (8.4 ± 0.8%, 5.0 ± 1.5%, respectively) compared with WKY rats (12.4 ± 0.6%, 15.8 ± 0.7%, respectively; P≤ 0.05). 3. Total RNA from rat vascular smooth muscle cells (VSMC) and endothelial cells (EC) were prepared with selective precipitation in 3 mol/L LiC1/6 mol/L urea. The expression of 11-HSD mRNA was confirmed in the rat VSMC but its mRNA expression was not detected in EC, using northern blot analysis. 4. The results in this study indicate that 11-HSD in the vascular wall may play a role in the pathogenesis of hypertension in SHR.     

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

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

12月龄自发性高血压大鼠肾动脉α1肾上腺素受体亚型与同龄WKY大鼠的比较

采用RNA酶保护分析法及离体血管收缩实验比较12月龄自发性高血压大鼠(SHR)和同龄WKY大鼠肾动脉α₁肾上腺素受体(α₁-AR)亚型. 功能实验结果表明去甲肾上腺素(NE)引起SHR肾动脉收缩的pD₂值和最大收缩反应与WKY大鼠相比没有显著差异. 但舍吲哚和WB4101抑制NE收缩SHR肾动脉的pA₂值与WKY大鼠相比显著增加,同时BMY7378抑制NE收缩SHR肾动脉的pA₂值与WKY大鼠相比无显著改变. 提示SHR肾动脉对NE的敏感性与WKY大鼠相比没有差异,但α_1A-AR在介导NE收缩SHR肾动脉中的作用与WKY大鼠相比增加. RNA酶保护分析法结果显示在SHR肾动脉α₁-AR三种亚型的mRNA水平与WKY大鼠相比没有显著改变. 提示α₁-AR亚型在介导收缩反应中的改变可能因受体蛋白水平和(或)受体后信号转导的改变所致.     

AGE-DEPENDENT ALTERATIONS IN VASCULAR SMOOTH MUSCLE CELL RESPONSIVENESS TO PLATELET-DERIVED GROWTH FACTOR IN GENETIC HYPERTENSION

1. This study examined and compared the growth characteristics of vascular smooth muscle cells (VSMC) isolated from 4 and 12 week old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats following stimulation with platelet-derived growth factor-BB (PDGF-BB). 2. Vascular smooth muscle cells from 4 week old SHR proliferated at a slower rate than VSMC isolated from 12 week old SHR (1.08±0.06/day vs 1.89±0.13/day respectively, P < 0.05). In contrast, there was no difference in the proliferation of VSMC from 4 and 12 week WKY rats (0.62±0.06/day vs 0.82±0.13/day, respectively, P>0.05). 3. The cell density at which VSMC from 4 and 12 week old SHR become refractory to the mitogenic effects of PDGF-BB was similar and approximately two-fold greater than VSMC from age-matched WKY rats. 4. This study concludes that there is an age-dependent, differential and specific upregulation of growth rate mechanisms in VSMC from SHR which enhance proliferation in response to PDGF-BB.     

Nitric oxide inhibits isoprenaline-induced positive inotropic effects in normal, but not in hypertrophied rat heart

Evidence has accumulated that, in the rat heart, nitric oxide (NO) inhibits β-adrenoceptor-mediated positive inotropic effects. The aim of this study was to investigate whether this effect of NO may be altered in cardiac hypertrophy. For this purpose we studied the effects of the NO-donor SNAP (S-nitroso-N-acetyl-D,L-penicillamine) on isoprenaline-induced positive inotropic effects in left ventricular strips from three models of cardiac hypertrophy: a) 12–16 weeks old male spontaneously hypertensive rats (SHR) vs. age-matched normotensive Wistar-Kyoto (WKY) rats, b) six weeks old male Wistar WKY-rats subtotally nephrectomized (SNX) 7 weeks after SNX vs. sham-operated rats (SOP) and c) four weeks old male Wistar WKY-rats supra-renal aortic-banded (AOB, band diameter 1.0 mm) 8 weeks after AOB vs. SOP. In all three models of cardiac hypertrophy the heart weight/body weight ratio was significantly higher than in their respective controls. On isolated electrically driven ventricular strips isoprenaline (10^–10–10^–5 M) caused concentration-dependent increases in force of contraction. Maximal increases (E_max) were similar in SHR vs. WKY-rats, but reduced in SNX- (2.9±0.29 vs. 5.1±0.34 mN, p<0.01) and AOB-rats (2.3±0.37 vs. 4.2±0.33 mN, p<0.01). In control rats (WKY and the respective SOP) the NO-donor SNAP (10^–5 M) caused a significant rightward-shift of the concentration-response curve for isoprenaline; this rightward-shift could be inhibited by methylene blue (10^–5 M). In ventricular strips of SHR, SNX- and AOB-rats, however, 10^–5 M SNAP failed to significantly affect isoprenaline-induced positive inotropic effect. We conclude that in cardiac hypertrophy effects of NO are attenuated. Such an impairement of the NO-system could contribute to the development and/or maintenance of cardiac hypertrophy. Received: 16 February 1998 / Accepted: 11 March 1998     

The α‐adrenoceptor antagonist,zolertine, inhibits α1D‐ and α1A‐adrenoceptor‐mediated vasoconstriction in vitro

1 The antagonist effect of zolertine (4‐phenyl‐1‐[2‐(5‐tetrazolyl)ethyl]piperazine trihydrochloride), on vascular contraction elicited by noradrenaline in aorta, carotid (α1D‐adrenoceptors), mesenteric (α1A/D‐adrenoceptors) and caudal arteries (α1A‐adrenoceptors) from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats and rabbit aorta (α1B‐adrenoceptors), was investigated in endothelium‐denuded arterial rings.
2 The selective α1D‐adrenoceptor agonist, noradrenaline, elicited concentration‐dependent contractions in all arterial rings from both species. Noradrenaline selectivity was: carotid=aorta>>.Gt;mesenteric=rabbit aorta>caudal arteries.
3 The contractile responses induced by noradrenaline were competitively antagonized by zolertine in rat carotid and aorta arteries, yielding pA2 values of WKY, 7.48±0.18; SHR, 7.43±0.13 and WKY, 7.57±0.24; SHR, 7.40±0.08, respectively. Zolertine was a non‐competitive antagonist in some blood vessels as Schild plot slopes were lower than unity. The pKb estimates for zolertine were WKY, 6.98±0.16; SHR, 6.81±0.18 in the mesenteric artery, WKY, 5.73±0.11; SHR, 5.87±0.25 in the caudal artery and 6.65±0.09 in rabbit aorta.
4 Competition binding experiments using the α1‐adrenoceptor antagonist [³H]prazosin showed a zolertine pKi of 6.81±0.02 in rat liver (α1B‐adrenoceptors) and 6.35±0.04 in rabbit liver (α1A‐adrenoceptors) membranes.
5 Zolertine showed higher affinity for α1D‐adrenoceptors compared to α1A‐adrenoceptors, while it had an intermediate affinity for α1B‐adrenoceptors. The ability of the α1‐adrenoceptor antagonist zolertine to block α1D‐adrenoceptor‐mediated constriction in different vessels of WKY and SHR rats may explain its antihypertensive efficacy despite its low order of potency.     

Scavenging of NADPH oxidase-derived superoxide anions improves depressed baroreflex sensitivity in spontaneously hypertensive rats

相似文献   

ANGIOTENSIN CONVERTING ENZYME INHIBITOR, CAPTOPRIL, INHIBITS CARDIAC HYPERTROPHY WITHOUT CHANGING COLLAGEN TYPES AND CONCENTRATION IN SPONTANEOUSLY HYPERTENSIVE RATS

1. The effects of the ACE inhibitor, captopril, on collagen metabolism in spontaneously hypertensive rats (SHR) with cardiac hypertrophy was examined. Captopril (100 mg/kg per day) was administered in drinking water to 20 week old male SHR for 12 weeks. Collagen concentration was calculated from hydroxyproline content, and relative proportions of types I, III and V collagen were determined by non-interrupted SDS-polyacrylamide gel electrophoresis (SDS-PAGE). These parameters were examined in age and sex matched Wistar-Kyoto (WKY) rats, as well as in non-treated SHR, and compared with those of captopril-treated SHR. 2. Captopril significantly reduced both blood pressure (191 ± 12.1 vs 146 ± 11.2 mmHg, P < 0.01), and the ratio of left ventricular (LV) weight to bodyweight (BW; 2.38 ± 0.17 vs 2.05 ± 0.12 mg/g, P < 0.01). There were no significant differences in collagen concentration among WKY rats, captopril-treated SHR and non-treated 32 week old SHR. However, total collagen content in captopril-treated SHR reduced significantly compared with non-treated 32 week old SHR (16.8 ± 2.0 vs 21.3 ± 0.8 mg, P < 0.01). The relative proportion of type V collagen was significantly higher in both captopril-treated (58.6 ± 3.4 vs 46.8 ± 1.3%, P < 0.01) and non-treated 32 week old SHR (59.9 ± 3.1 vs 46.8 ± 1.3%, P < 0.01) compared with WKY rats. However, there were no significant differences between captopril-treated SHR and non-treated 32 week old SHR. 3. The data from this study showed that captopril reduced cardiac hypertrophy, as reported previously, but did not change collagen types and concentration of the hypertrophied myocardium in SHR.     

Affinity Constants and β-Adrenoceptor Reserves for Isoprenaline on Cardiac Tissue from Normotensive and Hypertensive Rats

To determine whether there are differences in cardiac β-adrenoceptor responsiveness, isoprenaline affinity constants and fractional β-adrenoceptor occupancy—response relationships for isoprenaline in the early stages of established hypertension, we studied the effects of bromoacetylalprenololmenthane (BAAM) and ([3,5-diamino-6-chloro-N-(1[N-β-(2-hydroxyl-3-α-naphthoxypropylamino)ethylcarbamoyl]-1-methylethyl)-pyrazine-2-carboxamide (ICI 147 798), slowly reversible β-adrenoceptor antagonists, on the isoprenaline responses of the left ventricular papillary muscle and the left and right atria of 6-month-old Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The papillary muscles, but not the right and left atria, of the SHR were less responsive to isoprenaline than those of the WKY. The isoprenaline pD₂ values (the negative logarithms of the molar concentrations of agonist producing 50% of the maximum response) were 7.72 and 8.00 on the SHR and WKY papillary muscles, respectively. On the WKY papillary muscle the isoprenaline K_A values were 2–3 times 10^?6M, which is as expected for isoprenaline at β₁ or β₂-adrenoceptors. Isoprenaline had 100-fold greater affinity on the WKY and SHR left atria than on the papillary muscles; the isoprenaline K_A values were 2–4 times 10^?8M. On the WKY papillary muscle and left atrium, isoprenaline had to occupy 3–4% of the β-adrenoceptors to produce a 50% maximum response; on the WKY papillary muscle and left atrium isoprenaline had to occupy 25–35% and 55%, respectively, of the β-adrenoceptors to produce a 90% maximum response. The SHR papillary muscles and left atrium had smaller β-adrenoceptor reserves for isoprenaline than did the WKY tissues. We were unable to obtain isoprenaline K_A values on the WKY right atrium. The isoprenaline K_A value on the SHR right atrium was 1–4 times 10^?8M. Because the isoprenaline K_A values for the left and right atria are markedly different from those previously reported for isoprenaline at β₁ or β₂-adrenoceptors, we suggest that atypical β-adrenoceptors might be present on the atria of WKY and SHR. We have also demonstrated a lower β-adrenoceptor reserve on SHR papillary muscle and atria in the early stages of established hypertension.     

Nitric oxide-dependent hypotensive effects of adrenomedullin in rats

The association of nitric oxide (NO) with the hypotensive effects of adrenomedullin (AM) was investigated in anesthetized rats. Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were used at 11–13 weeks of age. Blood pressure and heart rate were measured from the femoral artery under mild anesthesia using pentobarbital. AM, over the dose range of 0.3–3 nmol/kg iv, produced dose-dependent sustained hypotension and compensatory tachycardia. These effects of AM at 0.3, 1, and 3 nmol/kg iv were significantly stronger in SHR (−9 ±4, −53 ±9, and −62 ±7 mmHg) than in WKY (−4 ±1, −16 ±2, and −22 ±2 mmHg). Those at 1 nmol/kg iv were markedly inhibited in SHR (−53 to −19 mmHg) and in WKY (−16 to −12 mmHg) by treatment with the nitric oxide synthase (NOS) inhibitor N^G-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg iv). On the other hand, the difference of hypotensive effects in WKY and SHR by calcitonin gene-related peptide (CGRP) and the inhibitory effect by the treatment with L-NAME were smaller than seen with AM. These effects of CGRP at 0.03, 0.1, 0.3, and 1 nmol/kg iv were in SHR (−7 ±2, −18 ±3, −42 ±4, and −74 ±3 mmHg) and in WKY (−7 ±1, −16 ±1, −26 ±3, and −41 ±2 mmHg), respectively. Those at 0.3 nmol/kg iv were not significantly inhibited in SHR (−42 to −43 mmHg) and in WKY (−26 to −20 mmHg) by treatment with L-NAME, 10 mg/kg iv. These results indicate that the AM hypotensive effect was more pronounced in the hypertensive state and strongly depends on NO synthesis. © 1996 Wiley-Liss, Inc.     

EFFECT OF TRANSFORMING GROWTH FACTOR-β1 ON PLATELET-DERIVED GROWTH FACTOR RECEPTOR BINDING AND GENE EXPRESSION IN VASCULAR SMOOTH MUSCLE CELLS FROM SHR AND WKY RATS

1. This study examined the effects of transforming growth factor-βl (TGF-β1) on platelet-derived growth factor-BB (PDGF-BB)-stimulated DNA synthesis, [¹²⁵I]-PDGF-BB receptor binding and PDGF-β receptor mRNA expression in vascular smooth muscle cells (VSMC) isolated from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. TGF-β1 inhibited by 40% DNA synthesis stimulated by PDGF-BB in VSMC from WKY rats but potentiated by 20% growth factor-stimulated DNA synthesis in VSMC from the SHR. 3. Since the difference in effect of TGF-β1 could not be attributed to differential regulation of [¹²⁵I]-PDGF-BB binding activity and PDGF-β receptor mRNA expression, it is suggested that alterations in intracellular signalling pathways may account for the differential effects of TGF-β1 on PDGF-BB-stimulated DNA synthesis in VSMC from SHR and WKY rats.     

高血压大鼠学习记忆障碍及降压药物疗效

目的：观察高血压大鼠学习记忆功能的损害并评价比较降压药物的治疗效果。方法：自发性高血压大鼠（ＳＨＲ，１６ｗｋ）分３组（ｎ＝６），其中两组分别使用尼群地平、卡托普利，另一组为对照组；肾血管性高血压Ｗｉｓｔａｒ－Ｋｙｏｔｏ（ＷＫＹ）大鼠（ＲＨＲ，１６ｗｋ）共６组（ｎ＝６），其中５组分别使用卡托普利、美多洛尔、普萘洛尔、硝苯地平、哌唑嗪，另一组不用药。再设一正常对照ＷＫＹ（１６ｗｋ，ｎ＝６）组。治疗８ｗｋ后，连续５ｄ进行跳台试验，每天１０次。结果：两种未经治疗的高血压大鼠ｄ５的主动回避反应计分均有不同程度的下降（ＳＨＲ：０．９±１．１，ＲＨＲ：４．２±１．２ｖｓ，ＷＫＹ：８．７±１．８，Ｐ均＜０．０１）；用药ＳＨＲ两组与对照ＳＨＲ组相比（３．６±１６，４．３±１．８ｖｓ０．９±１．１，Ｐ＜０．０５），记分明显改善；ＲＨＲ美多洛尔７．７±１．６，ＲＨＲ普萘洛尔８．３±１．９，ＲＨＲ卡托普利８．０±２．０，ＲＨＲ硝苯地平７．２±１．７，ＲＨＲ哌唑嗪７．３±１．７，与ＲＨＲ对照（４．２±１．２）比较，Ｐ均＜０．０１；主动回避反应计分有显著提高。进一步比较不同药物治疗组，当降压程度相似时，各组主动回避反应计分无明显差别。?     

ABNORMALITY OF THE GLOMERULAR ANGIOTENSIN II RECEPTOR IN EXPERIMENTAL DIABETIC NEPHROPATHY

1. The combined effect of diabetes and hypertension on the plasma angiotensin II (AII)/glomerular AII receptor (AII-R) relationship in streptozotocin-induced diabetes was investigated as well as the effect of glycaemic control on this relationship. 2. Diabetes was induced in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with streptozotocin 60 mg/kg and blood sugars maintained between 18–21 mmol/L (uncontrolled diabetes) and 4–8 mmol/L (controlled diabetes). Rats were killed on days 1 and 7. Angiotensin II receptor was estimated by saturation analysis and plasma AII by radio-immunoassay. 3. Angiotensin II receptors were significantly higher in non-diabetic SHR than WKY rats (708 ± 62 and 388 ± 36 fmol/mg protein, respectively, P = 0.0008). Plasma AII were comparable in both groups (47 ± 2.7, 38 ± 3.5 pg/mL, respectively) and a significant inverse relationship between AII/AII-R was observed (WKY P = 0.02 and SHR P = 0.004). 4. On day 7, plasma AII and AII-R levels in diabetic groups were comparable with those of their non-diabetic controls. Diabetic WKY rats maintained an inverse correlation between AII and AII-R (controlled P= 0.04 and uncontrolled P= 0.015), but this did not occur in the SHR. 5. Absence of receptor response to varying ligand concentrations in the diabetic SHR may contribute to the development of nephropathy. Glycaemic control does not appear to reverse this abnormality in the SHR, so that co-existent hypertension may have a more direct influence on renal function.     

Rosuvastatin Attenuates Heart Failure and Cardiac Remodelling in the Ageing Spontaneously Hypertensive Rat

Abstract: 3‐hydroxy‐3‐methylglutaryl(HMG)‐Coenzyme(Co)A reductase inhibitors such as rosuvastatin may improve clinical status in patients with hypertension and heart failure. The ageing spontaneously hypertensive rat (SHR) closely mimics the chronic heart failure disease process observed in humans. This study examined the structural and functional changes in the cardiovascular system of 15‐month‐old SHR and normotensive Wistar‐Kyoto (WKY) rats treated with rosuvastatin (20 mg/kg/day perorally) for 24 weeks. Cardiovascular structure and function were monitored serially by echocardiography. At 21 months, ex vivo Langendorff, electrophysiological or histological studies were performed. Chronic rosuvastatin treatment attenuated elevations of left ventricular wet weight (mg/g body weight: 21‐month WKY, 2.30 ± 0.04; 15‐month SHR, 3.03 ± 0.08; 21‐month SHR, 4.09 ± 0.10; 21‐month SHR + rosuvastatin, 3.50 ± 0.13), myocardial extracellular matrix content (% left ventricular area: 21‐month WKY, 7.6 ± 0.5; 15‐month SHR, 13.2 ± 0.8; 21‐month SHR 19.6 ± 1.0; 21‐month SHR with rosuvastatin 14.6 ± 1.2) and diastolic stiffness (κ: 21‐month WKY, 24.9 ± 0.6; 15‐month SHR, 26.4 ± 0.4; 21‐month SHR, 33.1 ± 0.8; 21‐month SHR + rosuvastatin, 27.5 ± 0.6) as well as attenuating the deterioration of systolic and diastolic function (fractional shortening %: 21‐month WKY, 66 ± 2; 15‐month SHR, 51 ± 3; 21‐month SHR, 38 ± 3; 21‐month SHR + rosuvastatin, 52 ± 4). There was no effect on the increased systolic blood pressure, plasma low‐density lipoprotein concentrations or the prolonged action potential duration. Thus, chronic rosuvastatin treatment may attenuate myocardial dysfunction in heart failure by preventing fibrosis.     

Sex and strain-based inflammatory response to repeated tobacco smoke exposure in spontaneously hypertensive and Wistar Kyoto rats

Context: Approximately four million people die every year from chronic obstructive pulmonary disease (COPD), with more than 80% of the cases attributed to smoking.

Object: The purpose of this study was to examine the rat strain and sex-related differences and the extended tobacco smoke exposure to induce lung injury and inflammation with the goal of finding a suitable rodent model to study COPD.

Methods: Male and female spontaneously hypertensive (SH) and male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or to tobacco smoke (TS: 90?mg/m³ particulate concentration) for 6?h/day, three days/week for 4 or 12 weeks.

Results: Male SH rats demonstrated an enhanced, persistent inflammatory response compared to female SH and male WKY rats with extended TS exposure. Following four weeks of TS exposure, male SH rats had significantly increased total leukocytes and macrophage numbers, levels of TNF-alpha and elevated lactate dehydrogenase activity in bronchoalveolar lavage fluid compared with female SH, male WKY rats and corresponding controls. After 12 weeks of TS exposure, male SH rats continued to show significant increase in inflammatory cells and TNF-alpha, as well as IL-6 mRNA lung expression. In addition, the alveolar airspace of male SH rats exposed to TS was significantly enlarged compared to their FA controls, female SH and WKY rats.

Conclusion: The male SH rat demonstrates greater cellular, inflammatory and structural changes highly reminiscent of COPD compared to female SH and male WKY rats, suggesting that the male SH rat is an optimal rodent model to study COPD.     

VASCULAR SMOOTH MUSCLE CELL PROLIFERATION IN SHR AND WKY RATS: EVIDENCE FOR SPECIFIC DIFFERENCES IN GROWTH INHIBITORY REGULATORY MECHANISMS

1. This study examined and compared the actions of transforming growth factor-β₁ (TGF-β₁), heparin, dexamethasone and interferon-γ on platelet-derived growth factor-BB (PDGF-BB)-stimulated proliferation of vascular smooth muscle cells (VSMC) from normotensive, Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Heparin, dexamethasone and interferon-γ all inhibited VSMC proliferation stimulated by PDGF-BB in both SHR and WKY rats. There was no difference (P>0.05) in their inhibitory effects, which varied between 40 and 85% for the different agents. 3. Similarly, TGF-β₁ inhibited PDGF-BB-stimulated VSMC proliferation in WKY rats by approximately 50%. In contrast, TGF-β₁ potentiated growth factor action on cell proliferation in the SHR by approximately 40%. 4. Specific TGF-β₁-stimulated regulatory mechanisms involved in the inhibition of proliferation are absent in SHR and this defect may contribute to the vascular hypertrophy which is apparent in genetic hypertension.     

Possible opioid receptor function changes in isolated atria of the spontaneously hypertensive rat

• 1.1. A comparison of the effects of various opioid peptides on the heart rates of self-paced right atria was made, as taken from spontaneously hypertensive (SHR), Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats at 4, 8, 12 and 16 weeks of age.
• 2.2. Beta-endorphin, dynorphin, met-enkephalin, DAGO and DADLE slightly decreased the spontaneously beating rate of all rat strains and ages, at 0.1 μM. Leu-enkephalin at 0.2 μM increased the spontaneous beating rate of SHR atria, but not that of atria from normotensive strains.
• 3.3. SHR atria were somewhat more sensitive than WKY atria to norepinephrine (NE)-induced positive chronotropy, but the differences were not statistically significant.
• 4.4. In the presence of mu, delta or kappa opioid receptor agonists, SHR atrial sensitivity to NE-induced chronotropy was enhanced at all ages studied. By contrast, NE chronotropy was not significantly altered by the opioids in normotensive rat atria.
• 5.5. Based on the above results, all the three major opioid receptor subtypes (mu, delta and kappa) appear to be present in rat atria but the function of these receptors appears to be greater in SHR than in WKY and SD atria.
• 6.6. The results suggest a possible involvement of altered opioid responsiveness in atria during hypertension development in SHR but the nature of this involvement appears to be complex and is not readily understandable on the basis of the present study.

     

RE-EVALUATION OF THE SA GENE IN SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS

1. To investigate whether the difference in the SA gene expression in the kidneys is causally related to the pathogenesis of hypertension, we reassessed the expression of the SA gene in the kidneys of the spontaneously hypertensive rat (SHR), its stroke-prone substrain (SHRSP) and Wistar-Kyoto (WKY) rat from different sources (SHR/Izm, SHRSP/Izm and WKY/ Izm from Izumo colony; SHR/Crj and WKY/Crj from Charles River Laboratories). 2. At the age of 5 weeks, high levels of the SA mRNA were expressed in the kidneys of SHRSP/Izm, SHR/Izm, SHR/Crj and WKY/Izm, while very low levels of the SA mRNA were observed in those of WKY/Crj. At the age of 8 weeks, the expression of the SA mRNA in the kidneys of WKY/Izm was at the same level as in those of SHRSP/Izm and two SHR strains. 3. Four genetic markers at the SA locus, an StuI restriction fragment length polymorphism and three microsatellite markers, were not polymorphic among Izumo strains of SHR, SHRSP and WKY rats. 4. In situ hybridization showed strong signals of the SA mRNA in the renal proximal tubules, while no positive signals were detected in the glomeruli. 5. Because WKY/Izm has normal blood pressure, our observations indicate that a simple difference of the SA gene expression in the kidney cannot be an explanation for the difference of blood pressure between SHR(SP)/Izm and WKY/Izm.     

氯沙坦对自发性高血压大鼠脑组织肾素血管紧张素系统的影响

目的　探讨氯沙坦对自发性高血压大鼠 (SHR)脑组织血管紧张素Ⅰ型受体 (AT1 R)mRNA的表达及脑组织局部肾素 血管紧张素系统 (RAS)活性的影响。方法　 6wk龄♂WKY和SHR各 1 6只分别随机分为氯沙坦用药组和生理盐水对照组 ,喂养 1 8wk后运用RT PCR法检测脑组织AT1 RmRNA的表达 ;放免法测定肾素活性 (RA)和血管紧张素Ⅱ(AngⅡ )的水平 ;紫外分光光度法测定血管紧张素转换酶活性 (ACEA)。结果　SHR组各部位脑组织AT1 RmRNA和血浆、下丘脑RA、AngⅡ、血清ACEA表达均高于WKY组(P <0 0 5) ;氯沙坦可降低各部位脑组织AT1 RmRNA的表达但升高血浆RA、AngⅡ ,对下丘脑RA、AngⅡ、ACEA则无明显影响。结论　SHR脑组织AT1 RmRNA的表达及循环和组织RAS活性增加可能与高血压的发生有关 ,氯沙坦可能通过降低脑组织AT1 RmRNA表达发挥脑保护作用