Different Mechanisms Maintaining High Blood Pressure in Chronic One-Kidney,One-Clip,and Two-Kidney,One-Clip Hypertensive Rats

To evaluate the difference of the blood pressure regulating mechanisms of chronic(12–14 weeks) one-kidney, one-clip(1K-1C) and chronic two-kidney, one-clip(2K-1C) hypertensive rats, we administered captopril, captopril plus indomethacin, and indomethacin to the rats. Pretreatment values of plasma renin concentration, plasma aldosterone concentration and urinary kallikrein excretion were significantly higher in 2K-1C than in 1K-1C hypertensive rats. Captopril-induced blood pressure reduction was greater in 2K-1C than in 1K-1C hypertensive rats. When captopril was administered to the rats treated with indomethacin, captopril-induced blood pressure reduction was attenuated only in 2K-1C hypertensive rats. Indomethacin produced renal impairment and further raised the blood pressure in 1K-1C hypertensive rats, but did not in 2K-1C hypertensive rats. These results suggest that the renin-angiotensin system functions to maintain high blood pressure more predominantly in chronic 2K-1C than in 1K-1C hypertensive rats. The renal kallikrein-kinin system is suppressed in chronic 1K-1C hypertensive rats but not in 2K-1C hypertensive rats. The renal prostaglandin system is more important for regulating the renal circulation in chronic 1K-1C than in 2K-1C hypertensive rats.     

Exaggerated Hypotensive Responses to Calcium Antagonists in Spontaneously Hypertensive Rats

The hypotensive effects of intravenous injection and infusion of diltiazem, 1- and d-verapamil were investigated in conscious and anaesthetized rats with spontaneous hypertension (SHR) and normal blood pressure (NT-WKY). The inhibitory actions of these calcium-influx blockers on the pressor responses to angiotensin II (AII) and noradrenaline (NA) were also examined in anaesthetized SHR and NT-WKY. The intravenous injections of these three drugs (0.03, 0.1, 0.3, 1.0 mg/kg) lowered mean arterial pressure (MAP) in a dose related manner in conscious NT-WKY and SHR. The small dose of the blockers administered by intravenous infusion (0.02 mg/kg per min) also decreased MAP in both groups. The potency of the antihypertensive action was in the order 1-verapamil>d-verapamil=diltiazem. The fall in blood pressure expressed as percentage of the intial MAP produced by the compounds was significantly enhanced in SHR compared to NT-WKY. The pressor responses to All (0.03, 0.1, 0.3, 1.0 ug/kg i.v.) were suppressed by the intravenous infusinon of 20 ug/kg per min with 1-verapamil but not with d-veramil, diltiazem and vehicle in NT-WKY, while no calcium blocker significantly diminished the vasopressor action of All in SHR. The pressor effects of NA (0.3, 1.0, 10.0 ug/kg i.v.) were inhibited with d-verapamil and vehicle in NT-WKY. Diltiazem reduced the response to NA in SHR but the other compounds (and d-verapamil) did not alter the pressor response to NA in SHR. The pressor responses to arginine vasopressin (3, 10, 30 and 100 mU/kg i.v.) were not altered by diltiazem infusion in either SHR or NT-WKY. It is concluded that these compounds are different in the potency of their hypotensive action and also the inhibition of the pressor responses to All and NA. Calcium entry blockers are more effective antihypertensive agents in SHR than in NT-WKY. It appears that their inhibitory effects on the responses to All and NA do not explain the exaggerated hypotensive responses in SHR.     

Norepinephrine Turnover in the Heart and Blood Vessels of Goldblatt Hypertensive Rats

The norepinephrine (NE) content, the uptake of [3H]NE, the turnover time, the turnover and the synthesis rate of the neurotransmitter in the heart and blood vessels were studied in the chronic phase of two kidney and one kidney Goldblatt renovascular hypertension, in the rat. Intact and sham operated animals were used as controls. Fifty percent of the rats subjected to renal clipping developed hypertension. This fact allowed us to compare changes in clip operated hypertensive and normotensive animals. The weight of the hearts and blood vessels was significantly increased in clip operated rats. Changes were greater in hypertensive animals. NE concentration and total content in the heart and in the artery wall were significantly decreased in the clipped rats. [3H]NE uptake was significantly diminished in the heart of experimental animals; in the artery wall, uptake was much lower than in the heart but no differences were observed between clip operated and sham animals. The turnover of NE was not different among control and clip operated rats either in the heart or in the blood vessels. Synthesis rate was lower in hypertensive animals than in their respective controls, explaining the lower concentration of the amine in cardiovascular tissues.     

In vivo Venular Changes with the Development of One-Kidney,one-Clip Hypertension in the Rat

Television microscopy was used to quantify in vivo resting venular diameters and the responses to topically applied norepinephrine in the cremaster muscle of two groups of urethan-chloralose anesthetized rats: normotensive rats (NT) and onekidney, one-clip Goldblatt hypertensive rats (1K1C). Observations were made two weeks after the surgery which was used to induce renovascular hypertension. At this stage, we have previously observed an increase in arteriolar reactivity (1). In the current study, mean arterial blood pressures for 1K1C (149±5 mmHg) were significantly higher than pressures for NT (102±3 mmHg). Venules were categorized by branching order and venular diameters were measured at three different levels of the microcirculation: first (1V), second (2V), and third order (3V) venules. Reactivity to norepinephrine at all venular levels in the 1K1C group was similar to that recorded for the NT group. Resting venular luminal diameters, however, were significantly smaller (20%) for large (1V) venules of the HT group (137±9 μm) compared to those for the NT group (171±10 μm). Thus, in contrast to previously reported data for arterioles, a structural venoconstriction and not an increase in venular reactivity appears to characterize the early vascular changes associated with this form of renovascular hypertension.     

In Vitro Vascular Reactivity to Endothelin: A Comparison Between Young and Old Normotensive and Hypertensive Rats

In this study we have investigated whether the vascular smooth muscle of a large capacitance artery of spontaneously hypertensive rats (SHR) is hyperresponsive to endothelin-1 and whether the arterial responsiveness to endothelin-1 is affected by aging. Isometric contractions of spirally cut aortic strips from SHR of 11, 22, 33 and 44 weeks of age and from age-matched WKY were measured in parallel. The vessels from SHR did not exhibit a greater responsiveness to endothelin-1 than those from WKY. No difference of responsiveness to the peptide was found among the arteries isolated from WKY of different ages. In contrast, a progressive decrease of responsiveness to endothelin-1 with aging was observed in SHR. This finding seems to be specific for endothelin-1, since the responsiveness to norepinephrine was unchanged. The significant decrease of aortic responsiveness in SHR with aging might be due to chronic hypertension and indicate desensitization to endothelin-1. The latter might be related to chronic in vivo hyperproduction of endothelin, either genetically determined or related to the hypertension-induced endothelial damage.     

双肾双夹易卒中型肾血管性高血压大鼠重要靶器官小窝蛋白的表达

目的 研究在高血压发展过程中重要靶器官组织信号蛋白小窝蛋白（Caveolin-1）的表达。方法 建立双肾双夹易卒中型肾血管性高血压大鼠动物模型，随机分为高血压组和假手术组，用Western blot的方法检测小窝蛋白在心、脑、肾血管中的表达。结果 2周末高血压组血压明显升高，4周末高血压组心脏体重比明显升高，高血压组重要靶器官心、脑、肾、血管中小窝蛋白的表达随高血压的时程发展明显减少。结论 双肾双夹易卒中型肾血管性高血压大鼠重要靶器官组织小窝蛋白表达减少，提示小窝蛋白信号途径可能参与高血压的发生发展，与高血压靶器官的损害有关。     

阿托伐他汀对压力负荷引起高血压大鼠心肌肌浆网钙泵活力的影响

目的观察阿托伐他汀对压力负荷增高所致左心室肥厚(LVH)和心肌肌浆网钙泵(SERCA)活力的影响。方法雄性SD大鼠50只随机分为假手术组、腹主动脉缩窄(AAC)组、阿托伐他汀10mg/(kg·d)(Ato10mg)、阿托伐他汀30mg/(kg·d)(Ato30mg)和氨氯地平5mg/(kg·d)组,每组10只。采用腹主动脉缩窄术建立LVH动物模型,灌胃法给药4周。鼠尾容积法测量收缩压,计算左心室质量指数(LVMI),即左心室质量/体质量(LVM/BM);HE染色检测心肌细胞平均直径;无极磷酸根法测定SERCA活力;双波长荧光分光光度计检测心肌细胞内Ca2+浓度。结果与假手术组相比,AAC组收缩压、LVMI、心肌细胞平均直径、细胞内Ca2+浓度均显著升高,心肌SERCA活力(4.0±0.6)比假手术组(6.4±0.8)μmol/(mgpro.h)明显降低(均P<0.05)。与AAC组比较,阿托伐他汀30mg组及氨氯地平组均能降低大鼠收缩压、LVMI、心肌细胞平均直径和细胞内Ca2+浓度,同时能明显提高心肌SERCA活力[Ato30mg组(4.9±0.4),氨氯地平组(4.8±0.5)比AAC组(4.0±0.6)...     

Effect of an Increased Cardiac Output on Vascular Responses to Vasoactive Agents in Two-Kidney,One-Clip Goldblatt Hypertension

The effect of the increased cardiac output of two-kidney, one-clip Goldblatt hypertension (2-KGH) on the altered vascular responses to vasoactive agents was examined in the conscious, chronically instrumented dog. The early stage of 2-KGH is characterized by an increased arterial pressure, an increased aortic flow, a decreased total peripheral resistance, and enhanced responses to angiotensin II and serotonin. As the aortic flow increases the responses to norepinephrine are enhanced, and the dilator responses to acetyl-choline and nitroglycerin are depressed. Aortic flow then returns to control values and the increased arterial pressure is maintained by an increase in peripheral resistance. When the increased aortic flow is prevented by occluding the vena cava to maintain flow at control values, the vascular responses to each of the agonists do not differ from that obtained when the aortic flow is elevated. Moreover, the temporal development and magnitude of the elevation in arterial pressure resulting from the increased vascular resistance is similar in dogs with an increased and normal aortic flows. The results suggest that increased aortic flow is not essential for the increased vascular resistance or the vascular changes in the canine model of 2-KGH.     

Water and Exchangeable Sodium in Goldblatt Two-Kidney,Two-Clip Hypertensive Rats

Exchangeable ²²Na (ExNa), total body water (TBW) and the inulin space (InSp) were determined in two kidney, two-clip (2K-2C) hypertensive and sham operated (normotensive) control rats 6–8 weeks after surgery. TBW (ml/kg lean body weight) was the same in hypertensive and sham rats. In contrast, ExNa (mEq/kglbw) and InSp (ml/kglbw) significantly increased (p < 0.01) in rats whose hypertension did not exceed 170 mmHg. Consequently, sham, moderate hypertensive (< 170mmHg) and severe hypertensive (< 170 mmHg) animals showed equal TBW but differed in body water distribution in that modrately hypertensive animals displayed a redistribution of water in favor of the extracellular space.     

Isolated Perfused Mesenteric Arteries of Hypertensive and Normotensive Rats; Response to Norepinephrine,Lysine Vasopressin and Angiotensin II

The aim of this study was to assess the pressure response of mesenteric arteries isolated from various hypertensive rat models to the 3 pressor agonists norepinephrine, lysinevasopressin and angiotensin II. The isolated mesenteric arterial beds were perfused with a Krebs-solution and then exposed to increasing doses of the 3 different pressor agents. Compared to Wistar Kyoto controls, spontaneously hypertensive rats exhibited a clearly enhanced vascular response to norepinephrine and lysine vasopressin but not to angiotensin II. In animals with hypertension produced by angiotensin II continuously released by an osmotic micropump, the vascular response to lysine vasopressin and angiotensin II was increased while that to norepinephrine was unchanged. Rats rendered hypertensive by the administration of deoxycorticosterone and salt exhibited an increased vascular response exclusively to angiotensin II. In all models taken together, the magnitude of the vascular response to norepinephrine and lysine vasopressin was related to the blood pressure of the intact animal but this was not the case for angiotensin II. These observations are not incompatible with the concept that changes in the vascular response are predominantly due to structural changes of the vascular wall. However, they suggest that more specific alterations of responsiveness of the vascular smooth muscle must also take place.     

Influence of Parathyroidectomy on Blood Pressure and Vascular Reactivity in Spontaneously Hypertensive Rats

We investigated the influence of parathyroidectomy (PTX) on blood pressure (BP) and hindlimb vascular reactivity to noradrenaline (NA) and vasopressin (AVP) in male spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKR). Three groups of SHR and WKR, respectively, were investigated: Sham-operated (SO) rats on a normal calcium intake (0.95%), SO rats on moderately elevated calcium intake (1.6% calcium diet) and PTX rats on the 1.6% calcium diet. At the end of the experiment (3 months), directly or indirectly measured BP was significantly lower in the PTX-SHR group on the 1.6% calcium diet than in SO-SHR on the same diet. In WKR groups, no changes of BP were recorded. Hindlimb perfusion with oxygenated Tyrode's     

高血压大鼠动脉平滑肌细胞钙超载与腺苷三磷酸酶

目的探讨自发性高血压大鼠(SHR)动脉血管平滑肌细胞钙超载与腺苷三磷酸酶(AT-Pase)的关系。方法组织块种植法培养SHR和Wistar-Kyoto(WKY)大鼠胸主动脉平滑肌细胞,应用流式细胞术、生化酶学方法和逆转录聚合酶链反应(RT-PCR)技术等检测SHR和WKY大鼠动脉平滑肌细胞内游离钙浓度([Ca2 ]i)、细胞膜Ca2 -ATPase和Na -K -ATPase活性及其mRNA表达水平。结果SHR动脉平滑肌细胞[Ca2 ]i浓度高于WKY大鼠[(307.7±32.1vs118.9±21.4)nmol/L,P<0.01)],Ca2 -ATPase和Na -K -ATPase活性低于WKY大鼠(1.3±0.2vs2.6±0.3;3.1±0.5vs4.9±0.5,P均<0.01),细胞质膜Ca2 -ATPase(plasmamembraneCa2 -ATPase,PMCA)亚型1和Na -K -ATPaseα1亚单位mRNA表达低于WKY大鼠(0.231±0.007vs0.403±0.021;0.253±0.028vs0.634±0.033,P均<0.01)。结论SHR动脉平滑肌细胞出现钙超载,其机制可能部分与细胞膜PMCA和Na -K -ATPase活性降低有关,两种ATPase功能降低可能是其基因转录水平下调的结果。     

氨氯地平与依那普利联用对肾性高血压大鼠主动脉重塑的影响

目的观察氨氯地平单用及联用依那普利对肾血管性高血压大鼠(RHR)主动脉重塑及主动脉平滑肌细胞膜钠泵、钙泵活性和钠泵а1亚单位及细胞质膜钙泵亚型1(PMCA1)mRNA表达的影响,探讨氨氯地平单用及联用依那普利改善动脉重塑的可能机制。方法建立"两肾一夹(2K1C)"肾性高血压大鼠模型,设立假手术组、模型组、氨氯地平组[5 mg/(kg.d)]、依那普利组[10 mg/(kg.d)]、氨氯地平+依那普利组[2.5 mg/(kg.d)+5 mg/(kg.d)],每组6只,药物连续干预6周。采用HE染色、免疫组织化学染色、Masson染色法检测主动脉中膜形态及结构变化并测量中膜厚度与腔径比(ML/LD)、中膜面积与管腔面积比(MA/LA),放射免疫法检测血管紧张素Ⅱ(AngⅡ)含量,酶学比色法检测细胞膜钠泵及钙泵活性,实时PCR法检测钠泵α1亚单位、PMCA1 mRNA表达水平。结果 RHR血压显著升高,主动脉ML/LD、MA/LA明显增加,中膜组织钠泵、钙泵活性及钠泵α1亚单位、PMCA1 mRNA表达水平明显降低(P<0.05或P<0.01)。氨氯地平及依那普利均能减小RHR主动脉ML/LD、MA/LA,改善平滑肌肥大和胶原沉积,且均能降低主动脉中膜AngⅡ水平并升高主动脉中膜钠泵、钙泵活性(均P<0.01)。氨氯地平可显著升高PMCA1 mRNA表达水平,依那普利上调钠泵α1亚单位、PMCA1 mRNA表达水平(均P<0.01)。氨氯地平及依那普利联合应用减小主动脉ML/LD、MA/LA,降低主动脉组织AngⅡ水平和升高钠泵、钙泵活性及PMCA1 mRNA表达水平存在协同作用(均P<0.01)。结论氨氯地平联用依那普利改善主动脉重塑优于两药单用,其机制可能与它们更有效阻断主动脉组织RAS,升高主动脉平滑肌细胞膜钠泵及钙泵活性有关。氨氯地平可能通过上调PMCA1 mRNA表达水平改善钙泵活性。     

The Effect of Calcium Channel Blockers on Moderate or Severe Albuminuria in Diabetic,Hypertensive Patients

ObjectivesInhibitors of the renin-angiotensin system are recommended for the management of albuminuria in patients with hypertension and diabetes mellitus, but there is little consensus about alternative therapies. Calcium channel blockers are recommended for the management of hypertension, but the data are controversial regarding their role in patients with albuminuria. This review was designed to assess the efficacy of calcium channel blockers compared with inhibitors of the renin-angiotensin system in decreasing albuminuria in diabetic, hypertensive patients with nephropathy.MethodsWe searched MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov for records that compared calcium channel blockers to inhibitors of the renin-angiotensin system and reported pre- and postintervention albuminuria measurements. Two reviewers independently screened abstracts for randomized, controlled trials in adults. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to select 29 trials from 855 records. We synthesized the data through a random-effects model.ResultsWe analyzed data from 2113 trial participants with hypertension and diabetes mellitus who had the equivalent of ≥30 mg/day of urinary albumin excretion. Inhibitors of the renin-angiotensin system were more effective than calcium channel blockers in decreasing albuminuria (standardized difference in means ?0.442; confidence interval, ?0.660 to ?0.225; P < .001). This finding was independent of the blood pressure response to treatment. There was no difference between the 2 drug classes regarding markers of renal function.ConclusionsInhibitors of the renin-angiotensin system are superior to calcium channel blockers for the reduction of albuminuria in nephropathy due to hypertension and diabetes mellitus. The net clinical benefit, however, is small.     

自发性高血压大鼠肾脏血管紧张素转换酶2 mRNA转录及其蛋白表达

目的 观察不同月龄自发性高血压大鼠(SHR)肾脏血管紧张素转换酶2(ACE2)mRNA转录及其蛋白表达,初步探讨ACE2在高血压发生、发展过程中的可能作用.方法 雄性SHR 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(S9)共5组,每组各6只,各组均有相应月龄匹配的Wistar-Kyoto(WKY)大鼠作对照.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);逆转录聚合酶链式反应(RT-PCR)法检测肾脏ACE2 mRNA的转录水平;免疫组化染色结合计算机图像分析方法 测定肾脏ACE2蛋白的表达水平.结果 1)SHR的SBP随着月龄的增加而上升,6月龄后趋于稳定.2)SHR和WKY肾脏ACE2蛋白和mRNA水平均随着月份的增加而增加,3月龄时达高峰,6月龄后趋于稳定;且SHR肾脏ACE2蛋白和mRNA水平均低于同龄的WKY.S1肾脏髓质内侧部ACE2免疫染色阳性面积百分比较皮质和髓质外侧部高,与1月后的分布相反.结论 1)SHR肾脏ACE2 mRNA和蛋白的表达水平比WKY大鼠低.2)大鼠肾脏ACE2 mRNA和蛋白的表达具有时间和部位分布上的差异.     

自发性高血压大鼠肾脏血管紧张素转换酶2 mRNA转录及其蛋白表达

目的观察不同月龄自发性高血压大鼠(SHR)肾脏血管紧张素转换酶2(ACE2) mRNA转录及其蛋白表达,初步探讨ACE2在高血压发生、发展过程中的可能作用。方法雄性SHR1月龄组(S1)、2月龄组(S2)、3月龄组(S3)、6月龄组(S6)和9月龄组(S9)共5组,每组各6只,各组均有相应月龄匹配的Wistar-Kyoto(WKY)大鼠作对照。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);逆转录聚合酶链式反应(RT-PCR)法检测肾脏ACE2 mRNA的转录水平;免疫组化染色结合计算机图像分析方法测定肾脏ACE2蛋白的表达水平。结果1)SHR的SBP随着月龄的增加而上升,6月龄后趋于稳定。2)SHR和WKY肾脏ACE2蛋白和 mRNA水平均随着月份的增加而增加,3月龄时达高峰,6月龄后趋于稳定;且SHR肾脏ACE2蛋白和 mRNA水平均低于同龄的WKY。S1肾脏髓质内侧部ACE2免疫染色阳性面积百分比较皮质和髓质外侧部高,与1月后的分布相反。结论1)SHR肾脏ACE2 mRNA和蛋白的表达水平比WKY大鼠低。2)大鼠肾脏ACE2 mRNA和蛋白的表达具有时间和部位分布上的差异。     

Increased Systemic Vascular Responsiveness to Catecholamines in Spontaneously Hypertensive Rats

Systemic vascular responsiveness to i.v. bolus injections of norepinephrine and tyramine was evaluated in adult male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Changes in total peripheral resistance (TPR) were used as an index of vascular response. Dose-response curves were plotted with ln-dose on the x-axis and percent of maximum change in TPR on the y-axis, and the following indices of responsivesness were used: slope, lnED₅₀, lnx-intercept, and maximum reponse. Measurements were made before and after ganglionic blockade with pentolinium (5 mg/kg, i.v.). Cardiac output for TPR calculations was obtained from an implanted flow probe on the ascending aorta. The slopes and maximum responses to norepinephrine and tyramine were greater in SHR v. WKY, P<.05, before and after pentolinium treatment. There were no significant differences in lnED₅₀ or lnx-intercept between WKY and SHR for tyramine and norepinephrine prior to pentolinium. After pentolinium lnED₅₀ and lnx-intercept were similar for SHR and WKY for norepinephrine, but were greater in SHR for tyramine. The results demonstrate an increased systemic vascular responsiveness to catecholamines in adult SHR secondary to structural changes in blood vessels.     

Sensitivity and Reactivity to Endothelin-1 in Mesenteric Beds and Aortic Rings of 4-Week-Old Spontaneously Hypertensive Rats

The vasoconstrictor effects of endothelin-1 were studied in perfused mesenteric vascular beds (MVB) and aortic rings of 4-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY). Mean blood pressure (124×4 vs. 97×3 mmHg) and initial perfusion pressure in the MVBs (25×2 vs. 19.7×1.2) were significantly higher in SHR. Reactivity to endothelin-1 was increased in MVBs of SHR, as indicated by the maximum perfusion pressure obtained (223 × 8 vs 155 × 7 mmHg, p > 0.001), whereas there was no significant difference in sensitivity between the two strains (EC₅₀ values: 50 × 12 and 80 × 15 pmol, respectively). By contrast, in aortic rings reactivity and sensitivity to endothelin-1 were similar in both strains, (EC₅₀ s: 1.8 × 0.12 and 1.4 × 0.1 nM). Reactivity to norepinephrine was increased in MVBs, but reduced in aortic rings of SHR. The unchanged sensitivity to endothelin-1 and the unspecifically increased reactivity in the MVBs of SHR to endothelin-1 and norepinephrine indicate rather a change in vascular structure and not a functional abnormality. These results suggest that hyperreactivity to endothelin-1 may not be a primary hypertensive mechanism in genetic hypertension.     

实验性高血压所致的基底动脉结构改变及血管紧张素转换酶抑制剂的影响

探讨高血压大鼠基底动脉结构的变化及血管紧张素转换酶抑制剂对其的影响。选用易卒中型肾血管性高血压大鼠模型 ,分为高血压组、卡托普利治疗组、假手术正常血压对照组。分别于肾动脉狭窄术后 4、8、12周处死动物 ,取基底动脉 ,制片后分别用光镜和透射电镜观察 ,并进行体视学定量分析。术后 4周时高血压组基底动脉光镜下无明显形态学变化 ,8周和 12周时中膜厚度、壁腔比值均比同时期正常血压对照组增加 ,有显著性差异 (P <0 .0 5 ) ;卡托普利治疗后中膜厚度、壁腔比值均小于高血压组 ,差异有显著性 (P <0 .0 5 )。术后 4周高血压组基底动脉平滑肌细胞间隙略增宽 ;术后 8周细胞器肿胀 ,部分溶解 ,间质轻度水肿 ;12周时平滑肌细胞肌丝变性、断裂、溶解 ,内质网扩张 ,线粒体部分空泡变性 ,细胞坏死。卡托普利组各时期超微结构改变不明显。表明高血压可致基底动脉肥厚和超微结构破坏 ,而卡托普利可以预防高血压所致的基底动脉结构破坏。     

Systemic and Regional Hemodynamics in Normotensive and Spontaneously Hypertensive Rats after Slow-Channel Calcium Blocker Nitrendipine

To determine the effects of the recently synthesized slow channel calcium blocker nitrendipine on systemic and regional hemodynamics, mean arterial pressure, heart rate, cardiac index and organ blood flow distribution were measured with the combined radioactive reference sample and microsphere techniques before and one hour after its oral administration (1 mg or 10 mg/kg). Twenty-week-old normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) conscious male rats were studied. At the 10 mg dose, nitrendipine exerted a hypotensive effect within 15 minutes, and this effect persisted throughout the study. After one hour, mean arterial pressure fell by 14 percent of pretreatment levels in WKY controls; it fell by 25 percent in SHR (p < 0.001). This action was mediated by a fall in total peripheral resistance index (p < 0.01) that was nonuniformly distributed to the organ circulations since blood flow was maintained or increased to brain, heart, kidneys, lungs, and adrenals, but decreased to skin. No change in cardiac index was observed.