Reflex cardiovascular responses to somatic stimulation in spontaneously hypertensive rats

OBJECTIVES: This study aimed to test whether the cardiovascular responses to somatic stimulation in spontaneously hypertensive rats (SHR) were enhanced compared with those in normotensive Wistar-Kyoto (WKY) rats, and to examine any role of the impaired baroreflex function in the hypertensive rats. METHODS: Experiments were done in anaesthetized SHR (n = 34) and WKY (n = 31). Baroreceptor reflexes were assessed by continuous infusion of incremental doses (5-30 microg/kg per min) of phenylephrine over a 3 min infusion period. Cardiovascular responses to sciatic nerve stimulation (5 s trains, 1 ms pulse duration, 400 microA intensity) were studied before and after baroreceptor deactivation. The latter was achieved either by carotid occlusion and cutting the vagi and aortic nerves (SHR, n = 28 and WKY rats, n = 27), or by complete baroreceptor denervation (SHR, n = 6 and WKY rats, n = 4). RESULTS: We confirmed that baroreceptor sensitivity was significantly lower in SHR (0.40 +/- 0.05 ms/mmHg) than in WKY rats (0.90 +/- 0.04 ms/mmHg). Sciatic nerve stimulation elicited significantly greater increases in mean arterial pressure (MAP) and in heart rate in SHR than in WKY rats (+32.5 +/- 1.9 mmHg versus +20.2 +/- 1.1 mmHg and +13.5 +/- 1.5 bpm versus +8.0 +/- 1.1 bpm, respectively). Following baroreceptor deactivation, the responses to the same sciatic nerve stimulation of MAP and heart rate in SHR (+38.5 +/- 2.4 mmHg and +15.5 +/- 1.5 bpm) were still significantly greater than those in WKY rats (+29.5 +/- 1.3 mmHg and +11.6 +/- 1.2 bpm). CONCLUSIONS: These results show that cardiovascular responses to sciatic nerve stimulation are increased in SHR compared to WKY rats, and that this increased reactivity to somatic stimuli in hypertensive rats does not depend upon the impairment in baroreflex function demonstrated in this strain.     

Central cardiovascular action of urotensin II in spontaneously hypertensive rats.

We have previously reported that urotensin II acts on the central nervous system to increase blood pressure in normotensive rats. In the present study, we have determined the central cardiovascular action of urotensin II in spontaneously hypertensive rats (SHR). Intracerebroventricular (ICV) injection of urotensin II elicited a dose-dependent increase in blood pressure in both SHR and normotensive Wistar-Kyoto rats (WKY). The changes in mean arterial pressure induced by ICV urotensin II at doses of 1 and 10 nmol in the WKY were 8 +/- 2 and 23 +/- 3 mmHg, respectively. ICV administration of urotensin II caused significantly greater increases in blood pressure in SHR (16 +/- 3 mmHg at 1 nmol and 35 +/- 3 mmHg at 10 nmol, respectively) compared with those in WKY. Urotensin II (10 nmol) elicited significant and comparable increases in heart rate in SHR (107 +/- 10 bpm) and WKY (101 +/- 21 bpm). Plasma epinephrine concentrations after ICV administration of 10 nmol urotensin II were 203 +/- 58 pmol/ml in SHR and 227 +/- 47 pmol/ml in WKY, which tended to be higher than those in artificial cerebrospinal fluid-injected rats (73+/- 7 and 87 +/- 28 pmol/ml, respectively, p < 0.1). The immunoreactivity of urotensin II receptor GPR 14 was expressed extensively in the glial cells within the brainstem, hypothalamus, and thalamus. These results suggest that central urotensin II may play a role in the pathogenesis of hypertension in SHR. Since GPR 14 was expressed in the glial cells of the brain, urotensin II may act as a neuromodulator to regulate blood pressure.     

自发性高血压大鼠运动降压与动脉压力反射敏感性的相关性

目的：探讨运动训练对自发性高血压大鼠（SHR）动脉压力反射（BRS）敏感性的影响及血压与BRS的相关性。方法：雄性SHR大鼠和正常血压Wistar大鼠各20只被随机各分成常态（安静）组和运动组,每组10只。两运动组大鼠进行8周跑台训练（20m／min,60min／d,6d／周）。采用尾套法测量清醒大鼠的收缩压（SBP）和心率（HR）。静脉注射苯肾上腺素（PE）和硝普钠（NP）分别诱发降压反射和升压反射,以反射前后的心率与平均动脉压变化值之比（HR／MAP）作为降压反射敏感性（BRS-PE）和升压反射敏感性（BRS-NP）指标。结果：8周运动结束时,SHR运动组静息SBP[（163．6±10．7）mmHg比（180．0±8．5）mmHg]和HR[（345．0±9．8）次／min比（368．4±13．3）次／mini较SHR常态组显著下降,P均〈0．01。Wistar运动组静息SBP与常态组无明显差异（P〉0．05）,但HR较常态组显著下降[（343．9±10．2）次／min比（362．2±13．0）次／min,P〈0．05]。SHR运动组的BRS．PEE（1．32±0．22）bpm／mmHg比（0．89±0．13）bpm／mmHg]和BRS—NP[（1．21±0．26）bpm／mmHg比（0．60±0．09）bpm／mmHg]较SHR常态组明显提高,P均〈0．01,但仍低于Wistar常态组的~RSVBRS—PE：（1．96±0．23）bpm／mm—Hg,BRS．NP：（1．32±0．17）bpm／mmHg]。Pearson线性相关分析显示,SHR常态组和运动组的平均动脉压与BRS呈显著负相关（r=-0．734,P〈0．01）。结论：运动训练能显著降低SHR的血压,它与运动改善压力反射敏感性有关,提示增强的压力反射功能可能是高血压运动疗法的重要机制。     

The effects of the intracerebroventricular administration of cimetidine on hemodynamics in conscious rats: relation to the sympathetic nervous system

Histamine H2-receptor antagonists administered into the central nervous system have been shown to increase arterial pressure (AP) in anaesthetized animals (Paakkari et al., 1982). Few studies have been reported on the effects of centrally administered cimetidine (CIM), one of the histamine H2-receptor antagonists, in conscious animals. However, the mechanism of the pressor action of histamine H2-receptor antagonists remains unclear. The present study was designed to investigate the hemodynamic effects of intracerebroventricular (i.c.v.) CIM and the interaction between the sympathetic nervous system and histamine receptor system in conscious rats. Male Wistar rats weighing 200 gr were prepared for the experiment under a conscious and minimally restricted state. Five micrograms of i.c.v. saline (SAL-ICV group, n = 5) did not produce significant changes in mean arterial pressure (MAP) or heart rate (HR) (MAP from 85.6 +/- 3.4 to 86.0 +/- 4.3 mmHg and HR from 395.0 +/- 13.9 to 395.2 +/- 8.2 bpm, respectively). Twenty micrograms of i.c.v. phenoxybenzamine (POB-ICV group, n = 6) decreased MAP from 95.8 +/- 4.1 to 85.2 +/- 3.1 mmHg, -10.7 +/- 2.2 mmHg as delta MAP, and increased HR from 392.5 +/- 8.5 to 435.3 +/- 13.9 bpm, +42.8 +/- 6.8 bpm as delta HR. Two-hundred micrograms of intravenous (i.v.) POB (POB-IV group, n = 5) also decreased MAP from 96.0 +/- 4.3 to 71.0 +/- 5.1 mmHg, -25.0 +/- 2.7 mmHg as delta MAP, and increased HR from 395.8 +/- 10.5 to 473.0 +/- 12.4 bpm, +77.2 +/- 7.6 bpm as delta HR. The changes in MAP and HR were much greater in the POB-IV group than those in the other two groups. The subsequent i.c.v. administration of 250 micrograms of CIM induced an increase in MAP (+19.4 +/- 1.7 mmHg as delta MAP) and a decrease in HR (-36.4 +/- 3.1 bpm as delta HR) in the SAL-ICV group, which continued for at least 30 minutes producing peak effects 2 minutes after i.c.v. administration of CIM. However, an elevation of MAP caused by i.c.v. CIM was much more inhibited in the POB-ICV group than in the POB-IV group (+2.5 +/- 0.7 mmHg as delta MAP in the POB-ICV group and +5.0 +/- 1.3 mmHg as delta MAP in the POB-IV group, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of ovariectomy on blood pressure and venous tone in female spontaneously hypertensive rats

BackgroundVenous capacitance plays an important role in circulatory homeostasis. A number of reports have suggested an effect of estrogen on venous function. This study tested the hypothesis that ovariectomy would increase venous tone in the female spontaneously hypertensive rat (SHR) via autonomic mechanisms.MethodsFive-week-old female SHR were subjected to sham operation (Sham) or ovariectomy (OVX). At 10 weeks of age, the rats were instrumented for the measurement of arterial and venous pressure. A balloon catheter was advanced into the right atrium. Mean circulatory filling pressure (MCFP), an index of venous tone, was calculated. Mean arterial pressure (MAP), heart rate (HR), and MCFP were recorded from conscious rats. Postsynaptic adrenergic responsiveness was assessed by constructing cumulative dose-response curves to norepinephrine (NE).ResultsMAP was not significantly affected by ovariectomy (Sham 127 +/- 6 mm Hg vs. OVX 130 +/- 3 mm Hg). HR also was not different between groups (Sham 409 +/- 11 bpm vs. OVX 399 +/- 12 bpm). Conversely, MCFP was significantly, but moderately, increased in OVX SHR (Sham 5.2 +/- 0.2 mm Hg vs. OVX 5.9 +/- 0.2 mm Hg). Ganglionic blockade produced marked decreases in MAP, HR, and MCFP in both groups; however, the responses were not different between groups. Infusion of NE caused dose-dependent increases in MAP and MCFP. There were no statistically significant differences in these responses between Sham and OVX SHR.ConclusionEndogenous ovarian hormones effect a small reduction in MCFP. This effect does not appear to be mediated by adrenergic mechanisms.American Journal of Hypertension (2008). doi 10.1038/ajh.2008.237American Journal of Hypertension (2008); 21, 9, 983-988. doi 10.1038/ajh.2008.237.     

Heart rate elevation and diabetic retinopathy in patients with type 2 diabetes mellitus and normoalbuminuria

To investigate the role of heart rate (HR) and blood pressure (BP) for diabetic retinopathy, 24-h ambulatory HR and BP were monitored for 162 in patients with type 2 diabetes and normoalbuminuria. The fundus was assessed as no retinopathy, simple diabetic retinopathy (SDR) and proliferative retinopathy (PDR). Comparing the highest with the lowest quartile of diabetic duration, the relative risk for retinopathy was 9.3 and for nocturnal HR, it was 3.6. Comparison among three retinopathy groups (no retinopathy, group 1, n=122; SDR, group 2, n=24; Pre-PDR or PDR, group 3, n=16) showed that 24-h and nocturnal HR were significantly higher in group 3 (80+/-9 and 71+/-9 beats per min) than in group 2 (73+/-8 and 64+/-8) and group 1 (72+/-7 and 60+/-7). In multiple logistic analysis, the odds ratio of diabetic duration and nocturnal HR to the existence of retinopathy was 1.17 (95% CI, 1.10-1.25, P=0.00001) and 1.11 (95% CI, 1.05-1.17, P=0.0002). We concluded that diabetic retinopathy is related to diabetic duration and high heart rate in type 2 diabetes mellitus with normoalbuminuria. Heart rate elevation may be a predictor of advanced retinopathy.     

The variability of baroreflex sensitivity in juvenile, spontaneously hypertensive rats

In this study the baroreflex sensitivity of conscious, juvenile, spontaneously hypertensive rats (SHRs) was compared. The study population consisted of 19 eight-week-old male SHRs. The baroreflex sensitivity was quantified as the derivative of the variation in heart rate (HR) and the variation of mean arterial pressure (baroreflex sensitivity = ΔHR/ΔMAP). MAP was manipulated with sodium nitroprusside (SNP) and phenylephrine (PHE), administered via an inserted cannula in the right femoral vein. The SHRs were divided into four groups: (1) low bradycardic baroreflex (LB) where the baroreflex gain (BG) was between 0 and -1 bpm/mmHg with PHE; (2) high bradycardic baroreflex (HB), where the BG was < -1 bpm/mmHg with PHE; (3) low tachycardic baroreflex (LT) where the BG was between 0 and 3 bpm/mmHg with SNP; (4) high tachycardic baroreflex (HT) where the BG was > 3 bpm/mmHg with SNP. We noted that 36.8% of the rats presented with an increased bradycardic reflex, while 27.8% demonstrated an attenuated tachycardic reflex. No significant alterations were noted regarding the basal MAP and HR. There were significant differences in the baroreflex sensitivity between SHRs in the same laboratory. One should be careful when interpreting studies employing the SHR as a research model.     

Endogenous melanocortin system activity contributes to the elevated arterial pressure in spontaneously hypertensive rats

Previous studies suggest that activation of the CNS melanocortin system reduces appetite while increasing sympathetic activity and arterial pressure. The present study tested whether endogenous activity of the CNS melanocortin 3/4 receptors (MC3/4-R) contributes to elevated arterial pressure in the spontaneously hypertensive rat (SHR), a model of hypertension with increased sympathetic activity. A cannula was placed in the lateral ventricle of male SHR and Wistar (WKY) rats for chronic intracerebroventricular (ICV) infusions (0.5 muL/h). Mean arterial pressure (MAP) and heart rate (HR) were recorded 24 hour/d using telemetry. After 5-day control period, rats were infused with MC3/4-R antagonist (SHU-9119, 1 nmol/h-ICV) for 12 days, followed by 5-day posttreatment period. MC3/4-R antagonism increased food intake in SHR by 90% and in WKY by 125%, resulting in marked weight gain, insulin resistance, and hyperleptinemia in SHR and WKY. Despite weight gain, MC3/4-R antagonism reduced HR in SHR and WKY ( approximately 40 bpm), while lowering MAP to a greater extent in SHR (-22+/-4 mm Hg) than WKY (-4+/-3 mm Hg). SHU9119 treatment failed to cause further reductions in MAP during chronic adrenergic blockade with propranolol and terazosin. These results suggest that endogenous activity of the CNS melanocortin system contributes to the maintenance of adrenergic tone and elevated arterial pressure in SHR even though mRNA levels for POMC and MC4R in the mediobasal hypothalamus were not increased compared to WKY. These results also support the hypothesis that weight gain does not raise arterial pressure in the absence of a functional MC3/4-R.     

Changes of blood pressure and heart rate during sexual activity in healthy adults

OBJECTIVE: This study is to observe the changes of blood pressure (BP), heart rate (HR), double product (DP) and heart rate variability during sexual activity in healthy adults before we cover patients with chronic cardiovascular disease. METHODS: Forty-nine participants grouped by sex, 22 males, aged 40.6+/-7.8 years; 27 females, aged 40.3+/-7.8 years, underwent simultaneous ambulatory monitoring of BP and HR for 24 h. During the monitoring period, sexual activity of the participants with man-on-top in their familiar environment was performed. Participants were requested to measure BP manually at the beginning of each sexual phase and three times after orgasm in every 10-min interval and 60 min after orgasm. For each individual, eight measuring values, respectively, about BP, HR, DP and heart rate variability were obtained from baseline to 1 h after orgasm. The data were statistically analyzed with paired t-test and the significant level was set at P<0.05. RESULTS: In both groups, the peak BP did not appear at orgasm, but at the beginning of plateau and dropped to baseline level at 10 min after orgasm (male 141.41+/-17.13/91.05+/-13.69 vs. 120.14+/-11.07/72.86+/-7.78 mmHg, female 121.67+/-16.61/77.37+/-15.03 vs. 109.37+/-10.54/67.19+/-9.41 mmHg). The peak HR occurred at the beginning of orgasm, and dropped to baseline level 10-20 min after orgasm (male 96.36+/-11.96 vs. 75.41+/-9.02 bpm, female 90.19+/-10.38 vs. 71.44+/-5.68 bpm). DP of both groups elevated at the beginning of plateau and orgasm then decreased to baseline level 10 min after orgasm (male 12964.27+/-2659.17 vs. 9134.09+/-1469.58 mmHg bpm, female 10044.48+/-1777.89 vs. 7841.30+/-1023.79 mmHg bpm). All the results showed that BP, HR and DP have mild to moderate changes during sexual activity in healthy adults. CONCLUSION: Using ambulatory technology to monitor BP and HR helps us to get the real data in participants during sexual activity. BP, HR and DP increase just slightly for a short time and recover to baseline level soon after sexual activity in healthy adults. The physical exhaustion during sexual activity is within the range of the daily-life workload.     

Effects of a new calcium channel blocker, azelnidipine, on systemic hemodynamics and renal sympathetic nerve activity in spontaneously hypertensive rats.

Antihypertensive treatment with dihydropyridine calcium channel blockers elicits sympathetic nerve activation, which may contribute to cardiovascular events. However, recent clinical studies showed that treatment with azelnidipine, a new dihydropyridine calcium channel blocker, significantly reduced blood pressure in hypertensive patients while either maintaining or actually decreasing heart rate (HR). In this study, we examined the effects of azelnidipine and amlodipine on systemic hemodynamics and renal sympathetic nerve activity (RSNA) in anesthetized spontaneously hypertensive rats (SHR). We also examined the effects of these agents on baroreflex functions by infusing phenylephrine (30 microg/kg/min, i.v.) and sodium nitroprusside (10 microg/kg/min, i.v.) into azelnidipine- or amlodipine-treated SHR. Fifty min after administration of azelnidipine (10 microg/kg/min for 10 min, i.v.), mean arterial pressure (MAP) significantly decreased from 153+/-5 to 122+/-5 mmHg; however, HR and integrated RSNA did not change significantly (from 352+/-9 to 353+/-10 beats/ min and 115+/-5% of baseline, respectively). Infusion of amlodipine (50 microg/kg/min for 10 min) elicited similar effects on MAP (from 152+/-5 to 120+/-4 mmHg). However, amlodipine significantly increased HR (from 351+/-9 to 375+/-11 beats/min) and integrated RSNA (165+/-5% of baseline). Analyses of baroreflex function curves revealed that azelnidipine-treated rats showed a smaller baroreflex function than amlodipine-treated rats (p<0.05). These data suggest that azelnidipine possesses sympathoinhibitory effects, which may be one reason why it had less pronounced effects on HR in hypertensive patients.     

Activation of the renin-angiotensin system and blood pressure variability in rats

This study was designed to assay, using spectral analysis, the influence of the renin-angiotensin system activation on the blood pressure variability. Rats were surgically prepared with a supra-renal catheter inserted via the left carotid artery to perform local infusions and with a femoral artery catheter to measure blood pressure (BP) and heart rate (HR). The beta-adrenoceptors stimulation by isoprenaline was used to increase the plasma renin activity (PRA). A first group (n = 8) was infused with isoprenaline (0, 0.003, 10, 100, 300 ng/kg/min) at a rate of 20 microL/min. A second group (n = 8) received a bolus of the angiotensin II (AII) AT1 receptor-antagonist valsartan (2 mg/kg/mL, i.a.) prior to isoprenaline infusions. Five groups were used for blood sampling (one group infused with one concentration of isoprenaline) to assay PRA and catecholamines (CA). BP recordings were analysed using the fast Fourier transforms (FFT) on 2048 points time series (204.8 s). Isoprenaline from the concentration of 10 ng/kg/min increased PRA with a maximum effect of 8.5 fold with the highest concentration (300 ng/kg/min, p < 0.05); CA were not modified. Isoprenaline amplified the low-frequency (LF: 0.02-0.20 Hz) component of the systolic BP (SBP) variability (10 ng/kg/min: 4.16 +/- 0.62 mmHg2 versus: 2.90 +/- 0.44 mmHg2 for control value, p < 0.05) even if it did not modify BP and HR levels. Isoprenaline lowered BP and had a tachycardic effect at concentrations > or = 100 ng/kg/mL (at 100 ng/kg/mL: SBP = 115 +/- 3 mmHg, HR = 464 +/- 15 bpm, versus control: SBP = 128 +/- 3 mmHg, HR = 351 +/- 7 bpm, p < 0.05). Valsartan modified neither BP levels nor BP variability but exerted a tachycardic effect (+25 bpm, p < 0.001). Valsartan prevented the amplification of the LF oscillations of SBP induced by isoprenaline (10 ng/kg/min: 2.53 +/- 0.38 mmHg2 versus: 2.20 +/- 0.25 mmHg2 for control value (valsartan), ns). We conclude that a moderate endogenous production of renin increases SBP variability in the LF range in the conscious rat. This effect which does not affect BP and HR levels is mediated by AII AT1 receptors and does not involve the sympathetic nervous system.     

Normal and borderline ambulatory arterial pressures. A new method for establishing reference values

Ambulatory arterial pressures, both systolic (SAP) and diastolic (DAP), together with heart rate were measured every 15 minutes during 24 hours, using a Spacelabs 5200 apparatus, in 168 male subjects of mean age 21 +/- 1 years. According to the WHO criteria, 72 subjects had normal arterial pressure (clinical DAP less than or equal to 90 mmHg, clinical SAP less than or equal to 140 mmHg), and 86 subjects had untreated borderline arterial hypertension (abnormal clinical pressures, with clinical DAP less than or equal to 95 mmHg and clinical SAP less than or equal to 160 mmHg). On the basis of the WHO criteria, a sizeable part of pressure profiles in the normal and hypertensive groups overlapped. The Mc Queen method, derived from cluster analysis, considerably reduces this overlap. The method defines and objective criterion which enables the subjects to be reclassified in cases where clinical and ambulatory pressures "contradict each other". Such reclassification applied in about 20% of our subjects. This leads to a new definition of reference groups based on both clinical pressure and ambulatory pressure profile. The WHO criteria remain the basis for this classification. The Mc Queen method may be used to define normal and borderline arterial pressure profiles in male and female subjects of different age-groups.     

Basal sympathetic nerve activity is enhanced with augmentation of baroreceptor reflex in Wistar fatty rats: a model of obesity-induced NIDDM.

AIM: Wistar fatty rats (WFR) develop mild hypertension associated with obesity, hyperglycaemia and hyperinsulinaemia, and are thus assumed to be a good model of insulin resistance-related hypertension. We determined whether the activity of the sympathetic nervous system and its baroreflex-mediated regulation are involved in the development of hypertension in this strain. METHODS: Renal sympathetic nerve activity (RSNA) was recorded in pre-hypertensive WFR (n = 8, age 12 weeks) and Wistar lean rats (WLR) (n = 8) during changes in arterial pressure by phenylephrine and nitroprusside infusion in the conscious state. Baroreflex control of RSNA and heart rate were examined by logistic function analysis. RESULTS: The mean arterial pressure (MAP) of WFR was similar to that of WLR (108 +/- 4 versus 101 +/- 2 mmHg, not significant). Basal RSNA was elevated in WFR compared with WLR (86 +/- 2 versus 51 +/- 2% maximum, P< 0.01). Baroreflex control of RSNA was shifted to higher pressure levels (mid-range, 119 +/- 4 versus 99 +/- 4 mmHg, P < 0.05) in WFR compared with WLR, in spite of similar MAP. However, baroreflex sensitivity concerning RSNA was greater in WFR than WLR (3.07 +/- 0.15 versus 1.63 +/- 0.12% maximum/mmHg, P < 0.01). Baroreflex control of heart rate was also shifted to higher pressure levels (mid-range 129 +/- 4 versus 100 +/- 5 mmHg, P < 0.01) and its sensitivity was increased in WFR compared with WLR (4.62 +/- 0.51 versus 3.16 +/- 0.10 bpm/mmHg, P< 0.05). CONCLUSION: These results suggest that baroreflex is not impaired in spite of elevation of blood pressure and that the raised sympathetic nerve activity may contribute to the development of hypertension in WFR.     

射频消融犬心脏第三脂肪垫消弱Bezold-Jarisch反射

目的观察射频消融犬心脏第3脂肪垫(上腔静脉与主动脉根部之间的脂肪垫,SVC-AO FP)对Bezold-Jarisch反射(BJR)及相关的血流动力学指标的影响。方法30只杂种犬麻醉后经右侧开胸,随机分为对照组(不消融)、消融组(消融SVC-AO FP),每组15只。经左室导管弹丸式推注藜芦定15μg/kg诱发BJR,比较两组推药前后心率(HR)、动脉压、左室压、左室压最大上升速率(+dp/dtmax)及最大下降速率(-dp/dtmax)的变化。结果推注藜芦定前两组的各项指标无显著差异(P>0.05),推注藜芦定后两组的各项指标均呈一过性下降,消融组HR的最大下降值ΔHR显著低于对照组(27.7±8.2次/分vs 93.3±18.4次/分,P<0.01),但动脉压、左室压及±dp/dtmax的最大下降值两组相比无显著差异(P>0.05)。结论射频消融犬SVC-AO FP能明显消弱藜芦定诱发的BJR的HR抑制,但不能消弱BJR的血管抑制。     

ST-segment depression in hypertensive patients is linked to elevations in blood pressure,pulse pressure and double product by 24-h Cardiotens monitoring

BACKGROUND: Various statements are made concerning peaks of heart rate (HR), blood pressure (BP) and double product (product of HR and systolic BP) as triggers for ST-segment depression. The aim of the present study was to identify determinants of ST-segment depression with a new ambulatory device for simultaneous 24-h electrocardiogram (ECG) and BP monitoring. METHODS: A total of 63 treated patients (63 +/- 9 years, 33 women and 30 men) with arterial hypertension and ischemic heart disease were studied with a new ambulatory 24-h BP measurement (ABPM) device evaluated according to the BHS protocol (Cardiotens, Meditech, Hungary). This device allows simultaneous ST-segment analysis with extra BP recordings triggered by episodes of ST-segment depression. RESULTS: ST-segment (Holter ECG) depression (> 1 mm and > 60 s) was demonstrated in 26 patients with a mean duration of 4.95 +/- 2.6 min and a peak in the early morning hours. All ST-segment depressions were silent and occurred during a significant increase of BP (15 +/- 11 mmHg systolic and 10 +/- 5 mmHg diastolic, compared with the mean ABPM values) and a significant increase of the double product from 10 921 +/- 2 395 (24-h mean) to 14 515 +/- 2329 (during ST-depression). The recorded systolic and diastolic BP (SBP, DBP) values from the pre ST-event were significant higher compared with 24-h values (153 +/- 19 versus 145 +/- 22 mmHg systolic, 83 +/- 12 versus 78 +/- 14 diastolic). The mean pulse pressure (PP) value in the group with ST-depression was significantly higher than in the group without ST changes (69 +/- 16 versus 58 +/- 10 mmHg; P < 0.005). A total of 73% of patients with ST-events compared with 35% without ST-events showed a PP >or= 60 mmHg (P = 0.025). CONCLUSION: Simultaneous ABPM and ST-segment analysis identifies episodes of silent myocardial ischemia during increases of BP and HR. Hypertensive patients with ischemic heart disease and ST events show higher mean pulse pressure values than are observed in patients without events. A PP of >or= 60 mmHg is linked to an increased risk of silent myocardial ischemias.     

Role of oxidative stress in the sex differences in blood pressure in spontaneously hypertensive rats

OBJECTIVE: The hypothesis was tested that differences in oxidative stress play a role in the sex differences in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). DESIGN AND METHODS: Male and female SHR [and Wistar-Kyoto (WKY) rats in the long-term study] (n = 6-12 per group) received tempol (30 mg/kg per day) or tap water for 6 weeks from 9 to 15 weeks of age or from birth until 15 weeks of age. Blood pressure [mean arterial pressure (MAP)] and kidney tissue F2-isoprostane (IsoP) were measured at 15 weeks of age. RESULTS: In SHR given tempol for 6 weeks, blood pressure and IsoP were reduced in males, but not in females. In SHR given tempol from birth, MAP was higher in SHR than WKY rats (SHR males, 181 +/- 2 mmHg; SHR females, 172 +/- 3 mmHg; WKY males, 100 +/- 2 mmHg; WKY females, 101 +/- 2 mmHg, P < 0.01), and tempol reduced MAP by 14% (156 +/- 3) and 26% (127 +/- 4) in male and female SHR, respectively, but had no effect on WKY rats. IsoP was higher in SHR than WKY rats and higher in male SHR than female SHR (SHR males, 5.18 +/- 0.23 ng/mg; SHR females, 3.71 +/- 0.19 ng/mg, P < 0.01; WKY males, 1.72 +/- 0.45 ng/mg; WKY females, 2.21 +/- 0.08 ng/mg, P < 0.05, compared with SHR). Tempol reduced IsoP in SHR to levels found in WKY rats, but had no effect on IsoP in WKY rats. CONCLUSIONS: Development of hypertension in SHR is mediated in part by oxidative stress independent of sex. Also, tempol is effective in reducing blood pressure in females only when given prior to the onset of hypertension.     

Long-term arterial pressure in spontaneously hypertensive rats is set by the kidney.

OBJECTIVES: We investigated whether arterial pressure in spontaneously hypertensive rats (SHR) can be normalized by a kidney graft from normotensive histocompatible donors. In addition, the effect of differential genetic predisposition to hypertension of recipients of an SHR kidney on the development of post-transplantation hypertension was studied. METHODS: SHR were transplanted with a kidney from congenic rats (BB.1K) homozygous for a 2 cM segment of SHR chromosome 20, including the major histocompatibility complex class Ia and class II genes. BB.1K and F1 hybrids (F1H, SHR x Wistar-Kyoto rats) were transplanted with an SHR kidney and the development of renal post-transplantation hypertension was monitored. RESULTS: Thirty days after renal transplantation, mean arterial pressure (MAP) was 116 +/- 4 mmHg in SHR with a BB.1K kidney (n = 8) versus 168 +/- 2 mmHg in sham-operated SHR (n = 10); P < 0.001. Cumulative renal sodium balance (mmol/100 g body weight) over 21 days after bilateral nephrectomy was 6.8 +/- 0.6 in SHR with a BB.1K kidney versus 10.8 +/- 1.6 in sham-operated SHR (P < 0.05). Within 60 days of transplantation, MAP increased in BB.1K and in F1H transplanted with an SHR kidney (n = 7 per group) by 38 +/- 5 mmHg and 43 +/- 8 mmHg, respectively. CONCLUSIONS: In SHR, arterial pressure can be normalized by a kidney graft from normotensive donors. The genetic predisposition of the recipients to hypertension does not modify the rate and the extent of the arterial pressure rise induced by an SHR kidney graft.     

Blood pressure surge on rising

OBJECTIVES: Since cardiovascular complications tend to occur more often in the morning, it is tempting to link this to the surge in blood pressure (BP) on rising. Our objective was to measure BP and heart rate (HR) on rising and compare values with those recorded immediately beforehand and seek variables related to marked changes in the two parameters in a cohort of initially untreated hypertensives. METHODS: The 24-h ambulatory BP measurement along with an accurate measurement of the BP on rising (either manually or automatically from the device coupled with a position sensor) was obtained in untreated hypertensives. Left ventricular mass was measured with echocardiography at baseline. Patients were then treated and followed by their general physician and news was obtained at regular intervals. RESULTS: A total of 507 patients with adequate recordings were included. Rising led to a mean increase of 14 mmHg in systolic blood pressure (SBP) and a 13 beats per minute (bpm) increase in HR. This elevation in BP on rising in the morning differed from the alteration in BP on normal changes in position. It was associated with left ventricular hypertrophy at baseline and an increased risk of future cardiovascular complications. CONCLUSIONS: Our study confirms the surge in BP on rising in the morning. This elevation in BP is accompanied by an acceleration in cardiac rhythm with no significant correlation between the two parameters. The increase in BP on rising was linked with the overall variability in BP, but was independent of the mean BP over 24 h. It was associated with an increased risk of cardiovascular complications independently of age and average 24-h SBP.     

Evidence for increased in vivo sodium-potassium pump activity and potassium efflux in skeletal muscle of spontaneously hypertensive rats

We have used 87Rb nuclear magnetic resonance spectroscopy (NMR) to study in vivo rubidium kinetics in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) controls, using rubidium as a marker for potassium. We gave 15 male, 13-week-old SHR, mean +/- s.d. blood pressure 180 +/- 10 mmHg, and 15 age-matched normotensive controls, mean blood pressure 120 +/- 9 mmHg, a daily dose of RbCl (2 mmol/kg intraperitoneally). We made repeated NMR measurements of skeletal muscle rubidium concentrations until steady state was reached. We then withdrew rubidium and made further measurements of rubidium concentrations, at intervals, for up to 1 week after the last injection. We also measured plasma and erythrocyte rubidium concentrations by flame atomic absorption spectroscopy at similar intervals after the withdrawal of rubidium. Rubidium concentrations rose at a faster rate in SHR skeletal muscle, but the steady-state muscle rubidium concentration was the same (45 mmol/l) in both SHR and WKY rats. There was also a threefold increase in the rate of rubidium efflux from both muscle and erythrocytes in SHR. These results are consistent with a marked increase in Na+,K(+)-ATPase activity and an increase in the rate of rubidium efflux in vivo in SHR. The increased rate of rubidium efflux in SHR could represent increased K+ efflux via calcium-activated K+ channels and/or result as part of cell volume regulation secondary to increased Na(+)-H+ antiporter activity.     

Baroreflex sensitivity improvement is associated with decreased oxidative stress in trained spontaneously hypertensive rat

BACKGROUND: Baroreflex sensitivity (BRS) impairment has been associated with endothelial dysfunction and oxidative stress. METHODS: Because exercise training could improve endothelial function in spontaneously hypertensive rats (SHR), the effect of moderate exercise training on oxidative stress and BRS was investigated. Groups were divided into sedentary and trained Wistar-Kyoto rats (S-WK, n = 7 and T-WK, n = 6) and SHR (S-SHR and T-SHR, n = 9 each). Exercise training was performed on a treadmill (5 days/week, 60 min, 10 weeks), and the lactate threshold (20 m/min) was used to determine moderate intensity. RESULTS: Exercise training reduced mean arterial pressure in WK and SHR (S-WK 127 +/- 4, T-WK 105 +/- 5, S-SHR 169 +/- 4 versus T-SHR 140 +/- 4 mmHg; P < 0.01). Baroreflex bradycardic (S-WK -1.89 +/- 0.15, T-WK -2.11 +/- 0.37, S-SHR -0.80 +/- 0.09 versus T-SHR -1.29 +/- 0.10 bpm/mmHg; P < 0.0001) and tachycardic (S-WK 2.57 +/- 0.19, T-WK 2.73 +/- 0.21, S-SHR 1.18 +/- 0.07 versus T-SHR 2.02 +/- 0.10 bpm/mmHg; P < 0.0001) responses were significantly different between groups. Lipoperoxidation in erythrocytes (S-WK 11 320 +/- 739, T-WK 10 397 +/- 765, S-SHR 20 511 +/- 1627 versus T-SHR 10 211 +/- 589 counts per second (cps)/mg haemoglobin; P < 0.0001) and aortas (S-WK 12 424 +/- 2219, T-WK 7917 +/- 726, S-SHR 26 957 +/- 1772 versus T-SHR 17 777 +/- 1923 cps/mg protein; P < 0.0001) was reduced in T-SHR compared with S-SHR. Inverse correlations were observed between both bradycardic and tachycardic responses and lipoperoxidation in erythrocytes (r = 0.56 and r = -0.77, respectively; P < 0.01) and aortas (r = 0.77 and r = -0.80, respectively; P < 0.0001). CONCLUSION: Our results indicate that exercise training decreases oxidative stress, which is related to an improvement in BRS in SHR.