Radiotelemetric versus externalized catheter monitoring of blood pressure: effect of vasopressin in spontaneous hypertension

The changes in arterial pressure that follow withdrawal of a 3-h intravenous infusion of arginine vasopressin (AVP; 20 ng/kg/min) in spontaneously hypertensive rats (SHR) were monitored by radiotelemetry or conventional externalized femoral arterial catheters connected to pressure transducers. Baseline control arterial pressure was lower in the telemetry group compared to the externalized group. After withdrawal of the AVP infusion, blood pressure fell below preinfusion levels in both groups but the decrease was much less in the telemetry group. Strikingly, absolute blood pressure values recorded both during and after the vasopressin infusion were remarkably similar in the two groups. Responses in rats with externalized catheters implanted 7 days before infusion of AVP, a protocol similar to the telemetry group, were similar to those in rats with catheters implanted 24 h earlier. Blood pressure remained decreased in SHR infused with AVP for several days with complete recovery requiring 6-7 days. In contrast, physical activity decreased only on the first day following withdrawal of the infusion. Thus, the mechanism accounting for the blood pressure decrease must be of a long duration and unrelated to a change in gross physical activity. The results emphasize the value of radiotelemetry for recording blood pressure responses.     

Combined effect of sildenafil and guanethidine,propranolol or verapamil on erectile function in rats

Objectives This study aims to further elucidate the role of adrenergic transmission in erection and to highlight whether adrenergic transmission in the penis modulates sildenafil's action. Methods measurement of intracavernosal pressure in the anesthetized rat model. Key findings Guanethidine (3 and 6 mg/kg) potentiated intracavernosal pressure/mean arterial pressure (ICP/MAP) rises in response to cavernous nerve stimulation by 4.375 ± 0.425 and 18.375 ± 1.085% respectively. Propranolol did the opposite. In presence of guanethidine, sildenafil (0.01, 0.1 and 1 mg/kg) potentiated ICP/MAP responses by 81.571 ± 4.918%, 147.83 ± 10.864% and 279.285 ± 23.053% at 1 Hz compared to 22.277 ± 2.139%, 123.571 ± 8.443% and 186.25 ± 13.542% respectively in the absence of guanethidine. Propranolol inhibited the effect sildenafil at all frequencies of stimulation. Verapamil exhibited a pro‐erectile action and potentiated the effect of sildenafil (0.01, 0.1 and 1 mg/kg) on erectile responses corresponding to 85.25 ± 6.716%, 146 ± 11.288% and 221.571 ± 19.032% respectively compared to 26.011 ± 1.911%, 87.142 ± 8.73% and 182.2 ± 16.921% in its absence. Conclusions This study provides functional evidence that inhibition of sympathetic tone peripherally results in enhancement of erectile function. β‐adrenergic receptors seem to play an important role in erection. The combination of sildenafil and guanethidine or verapamil could have a potential advantage on erectile function but propranolol may mask the effect of sildenafil on erectile function.     

杨桃根醇提物对正常大鼠血压的影响

目的 研究杨桃根Averrhoa carambola root醇提物对正常大鼠血压的影响.方法 40只正常大鼠随机均分为5组:阳性对照组、正常对照组及杨桃根醇提物高、中、低剂量组.大鼠麻醉后以颈总动脉插管法连接心功能分析系统,待颈动脉血压稳定10 min后,测定给药前和十二指肠给药后30、60、90、120、150、180、210、240 min时大鼠的心率、收缩压、舒张压和平均动脉压.结果 杨桃根醇提物高剂量组大鼠的收缩压、舒张压、平均压分别于给药后60 min(由119.06±11.45 mmHg降至112.58±12.27 mmHg)、60 min(由110.91 ±9.83 mmHg降至95.44±14.82 mmHg)、90 min(由115.94±12.92 mmHg降至94.58±12.23 mmHg)开始降低;中剂量组大鼠的收缩压、舒张压、平均压分别于给药后150 min(由122.01±13.52 mmHg降至100.87 ± 15.04 mmHg)、90 min(由110.88 ± 13.75 mmHg降至89.52±17.91 mmHg)、90 min(由115.39±11.61 mmHg降至99.72±12.67 mmHg)开始降低.杨桃根醇提物对正常大鼠的心率无明显影响.结论 杨桃根醇提物能降低正常大鼠的血压.     

Endothelial cationic amino acid transporter‐1 overexpression blunts the effects of oxidative stress on pressor responses to behavioural stress in mice

Observational studies indicate that psychological stress may contribute to the pathogenesis of hypertension and this may be further accentuated by factors such as endothelial dysfunction. On this basis, we aimed to determine whether oxidative stress enhances pressor responses to stressful stimuli and whether augmenting endothelial function by increasing the transport of l ‐arginine can counter the effects of oxidative stress. Telemetry probes were used to measure mean arterial pressure (MAP) in wild‐type (WT; n = 6) and endothelial cationic amino acid transporter‐1 (CAT‐1)‐overexpressing (CAT+) mice (n = 6) before and during an aversive (restraint) and non‐aversive (almond feeding) stressor. The superoxide dismutase inhibitor diethyldithiocarbamic acid (DETCA; 30 mg/kg per day; 14 days) was then administered via a minipump to induce oxidative stress. Stress responses to feeding and restraint were repeated during Days 11–12 of DETCA infusion. In WT mice, pressor responses to restraint and feeding were augmented during infusion of DETCA (35 ± 1 and 28 ± 1 mmHg, respectively) compared with respective pretreatment responses (28 ± 2 and 24 ± 1 mmHg, respectively; P ≤ 0.01). In CAT+ mice, pressor responses to feeding were blunted during DETCA (20 ± 1 mmHg) compared with the control response (23 ± 1 mmHg; P = 0.03). In these mice, pressor responses to restraint were similar before (28 ± 1 mmHg) and during (26 ± 1 mmHg) DETCA infusion (P = 0.26). We conclude that endothelial CAT‐1 overexpression can counter the ability of oxidative stress to augment pressor responses to behavioural stress.     

Involvement of sinoaortic afferents in renal sympathoinhibition and vasodilation induced by acute hypernatremia

Despite the abundance of evidence that supports the important role of aortic and carotid afferents to short‐term regulation of blood pressure and detection of variation in the arterial PO₂, PCO₂ and pH, relatively little is known regarding the role of these afferents during changes in the volume and composition of extracellular compartments. The present study sought to determine the involvement of these afferents in the renal vasodilation and sympathoinhibition induced by hypertonic saline (HS) infusion. Sinoaortic‐denervated and sham male Wistar rats were anaesthetised with intravenous (i.v.) urethane (1.2 g/kg body weight (bw)) prior to the measurement of the mean arterial pressure (MAP), renal vascular conductance (RVC) and renal sympathetic nerve activity (RSNA). In the sham group, the HS infusion (3 mol/L NaCl, 1.8 mL/kg bw, i.v.) induced transient hypertension (12 ± 4 mmHg from baseline, peak at 10 min; P < 0.05), an increase in RVC (127 ± 9% and 150 ± 13% from baseline, at 20 and 60 min respectively; P < 0.05) and a decrease in RSNA (?34 ± 10% and ?29 ± 5% from baseline, at 10 and 60 min respectively; P < 0.05). In sinoaortic‐denervated rats, HS infusion promoted a sustained pressor response (30 ± 5 and 17 ± 6 mmHg of baseline values, at 10 and 30 min respectively; P < 0.05) and abolished the increase in RVC (85 ± 8% from baseline, at 10 min) and decrease in RSNA (?4 ± 3% from baseline, at 10 min). These results suggest that aortic and carotid afferents are involved in cardiovascular and renal sympathoinhibition responses induced by acute hypernatremia.     

Primary human sinonasal epithelial cell culture model for topical drug delivery in patients with chronic rhinosinusitis with nasal polyposis

Objectives The primary human sinonasal epithelial cell culture (HSNEC) allows for in‐vitro modelling of mucosal responses to topical therapy. Cultures grown from healthy donors may underestimate changes in individuals with chronic sinonasal disease thereby yielding inaccurate results with respect to this large patient population. The purpose of this study was to analyse HSNECs derived from patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) to determine whether expected disease dependent variables salient to topical drug delivery persist in culture. Methods Cultures were grown from patients with CRSwNP. Ciliary beat frequency (CBF) (basal and stimulated), permeability (trans and paracellular), inflammatory response, and glucocorticoid dose response were measured and compared with healthy controls. Key findings Methylcholine stimulated CBF was greater in CRSwNP versus controls (ΔCBF_60min 7.25 ± 1.02 vs 0.89 ± 1.04 Hz, respectively). Paracellular permeability was greater in CRSwNP versus controls (basolateral dextran_120min 18.97 ± 3.90 vs 11.31 ± 4.35 µg/ml, respectively). Lipopolysaccharide (0.1 mg/ml) stimulated interleukin‐6 (IL‐6) and IL‐8 secretion was increased in CRSwNP versus controls (IL‐6 Δbaseline 1738.72 ± 654.82 vs 1461.61 ± 533.51%, respectively; IL‐8 Δbaseline 137.11 ± 0.83 vs 111.27 ± 0.67%, respectively). CRSwNP cultures were more sensitive than controls to dexamethasone (1 µg/ml) dependent IL‐6 and IL‐8 suppression. Conclusions HSNECs derived from patients with CRSwNP retained their primary phenotype with respect to ciliary function, epithelial permeability, irritant induced inflammatory cytokine secretion, and glucocorticoid dose response.     

Non‐adrenergic,non‐cholinergic,non‐purinergic contractions of the urothelium/lamina propria of the pig bladder

相似文献   

RENAL AUTOTRANSPLANTS IN SHEEP: INVESTIGATION OF RENAL FUNCTION AND RENOVASCULAR HYPERTENSION

1. A novel surgical preparation of sheep with a cervical renal autotransplant has been developed. 2. Glomerular filtration rate and effective renal plasma flow were 25.1 ± 1.0 ml/min and 208 ± 10 ml/min respectively (n= 26). 3. The responses to water load and deprivation, to AVP injection, to Na depletion and intravenous hypertonic saline load show the kidneys responded in an appropriate physiological manner. 4. Constriction of the carotid-renal artery to reduce mean renal arterial pressure to 23 ± 4 mmHg (n= 4) resulted in an increase in systemic mean arterial pressure from 70 ± 4 mmHg to 75 ± 4 mmHg within 5 min. Systemic blood pressure further increased to 110 ± 7 mmHg with 2 h of constriction, when renal arterial pressure had increased to 45 ± 2 mmHg.     

Longitudinal assessment of the effects of oestrogen on blood pressure and cardiovascular autonomic activity in female rats

• 1 Published data concerning the effects of ovarian hormones on haemodynamic variability are contradictory. For the first time, the present study used radiotelemetric haemodynamic monitoring to investigate the long‐term effects of chronic oestrogen depletion and repletion on cardiovascular autonomic control and arterial baroreflex sensitivity (BRS) in female rats.
• 2 Blood pressure (BP), heart rate (HR) and +dP/dt_max of arterial pressure (an estimate of myocardial contractility) were monitored in sham‐operated (SO), ovariectomized (OVX) and oestrogen‐replaced OVX rats (OVXE2) for 16 weeks. Cardiovascular autonomic control and baroreflexes were assessed by frequency domain analysis of interbeat intervals (IBI) and systolic BP (SBP).
• 3 Compared with SO rats, OVX rats exhibited no changes in BP, short‐lived decreases in HR and sustained reductions in +dP/dt_max of arterial pressure. The high‐ (HF; 0.75–3 Hz) and low‐frequency (LF; 0.25–0.75 Hz) components of spectral power of IBI were significantly decreased and increased, respectively, by ovariectomy. An increase in the IBI_LF/HF ratio in OVX rats suggests a shift in the cardiac sympathovagal balance towards sympathetic dominance. Index α, the spectral index of spontaneous BRS, was reduced by OVX.
• 4 Oestrogen replacement caused significant reductions in BP and HR and reversed OVX‐induced changes in +dP/dt_max of arterial pressure and cardiac autonomic activity. The LF oscillations of SBP were reduced in OVXE2 rats, suggesting a reduction in vascular sympathetic tone by oestrogen.
• 5 These findings highlight the importance of long‐term oestrogen therapy in rectifying the detrimental effects of depletion of ovarian hormones on the cardiovascular system and baroreflex.

     

The glucocorticoid receptor is required for experimental adrenocorticotrophic hormone‐induced hypertension in mice

1. In the present study, we have (i) measured basal blood pressure by telemetry in wild‐type (WT) and glucocorticoid receptor knockout (GRKO) mice; (ii) investigated whether or not adrenocorticotrophic hormone (ACTH) can induce hypertension in GRKO mice; and (iii) investigated the effect of mineralocortocoid receptor blockade on the cardiovascular physiology of GRKO mice. 2. Male WT and GRKO mice were treated with ACTH (2 mg/kg per day s.c.) or spironolactone (100 mg/kg per day s.c.) for 1–2 weeks. Blood pressure (BP) was measured using a radiotelemetry system. Urinary Na : K, blood glucose concentrations and haematocrit were also measured during the treatment period. 3. Baseline systolic blood pressure (SBP) was higher in GRKO mice (126 ± 4 mmHg, mean ± SEM, n = 11) than WT mice (114 ± 2 mmHg, n = 10; P < 0.05). There was no significant difference in baseline haematocrit, blood glucose and urine Na : K ratio in WT and GRKO mice. ACTH raised SBP in WT (135 ± 8 mmHg, n = 8; P < 0.05), but not in GRKO mice (113 ± 9 mmHg, n = 6). Spironolactone treatment did not alter SBP. 4. Basal SBP was higher in GRKO than WT mice; ACTH raised blood pressure in WT, but not GRKO mice; and spironolactone did not alter BP in GRKO or WT mice. These data, together with a previous study showing both ACTH and corticosterone are increased in GRKO mice, show that the GR is required for the development of ACTH‐induced hypertension in mice. Increased endogenous ACTH levels in this model might contribute to the increased basal SBP in GRKO mice, possibly through residual fragments of GR. Mineralocorticoid receptors do not appear to play a critical role in maintaining BP in glucocorticoid receptor deficient mice.     

Cardiovascular effects induced by N-(4'-dihydro)-piperoylthiomorpholine in normotensive rats

Objectives We have tested the cardiovascular effects of N‐(4′‐dihydro)‐piperoylthiomorpholine (LASSBio 365) on rats using an in‐vivo and in‐vitro approach. Methods LASSBio 365 (0.025, 0.05, 0.1, 0.25, 0.5 or 1 mg/kg, randomly injected) was administered to conscious unrestrained rats and the mean arterial pressure and heart rate were measured. The effects of LASSBio 365 (3 × 10^?6–3 × 10^?4m ) on rat isolated aortic rings with and without endothelium were investigated. Key findings LASSBio 365 induced a dose‐dependent decrease in mean arterial pressure and heart rate (ED50 = 158 ± 53 µg/kg). The effects evoked by LASSBio 365 (0.5 mg/kg) were inhibited by pretreatment with atropine. In anaesthetized rats, electrocardiogram recordings revealed second/third degree sinoatrial and atrioventricular blockade induced by the compound, which were completely inhibited after cardiac muscarinic blockade or cervical bilateral vagotomy. In rat isolated aortic rings, LASSBio 365 (3 × 10^?6–3 × 10^?4m ) was capable of antagonizing the contractile effects induced by phenylephrine (1 µm ) or KCl (80 mm ) (IC50 = 107 ± 6; 92 ± 6 µm , respectively). This effect was not inhibited after removal of the vascular endothelium (IC50 = 84 ± 4; 92 ± 10 µm , respectively). LASSBio 365 (10^?6–10^?4m ) antagonized CaCl₂‐induced contractions in a concentration‐dependent manner. Furthermore, LASSBio 365 (98 µm ) inhibited contractions produced by noradrenaline (1 µm ), but not those induced by caffeine (20 mm ). Conclusions These results suggested that LASSBio 365 produced negative chronotropism and reduced peripheral resistance that were probably due to the stimulation of cardiac muscarinic pathways. Peripheral vasodilation was probably linked to voltage‐dependent Ca²⁺‐channel blockade and/or specific inhibition of Ca²⁺ release from noradrenaline‐sensitive intracellular stores.     

多沙唑嗪对映体对大鼠血压和排尿功能的影响

目的观察十二指肠给予多沙唑嗪(rac-DOX)及其对映体(S-DOX、R-DOX)对麻醉大鼠血压和膀胱排尿功能的影响。方法采用八道生理仪记录麻醉大鼠颈总动脉血压、心率以及膀胱排尿压、排尿间隔,并测量排尿量。结果十二指肠给予S-DOX、R-DOX和rac-DOX均可剂量依赖性降低颈总动脉收缩压、舒张压和平均动脉压,1.0mg.kg-1时3者对平均动脉压的降低幅度分别达到23.5%±4.6%、38.5%±8.9%和42.6%±7.5%,3者降低平均动脉压的ED30值依次为(2.0±0.8)、(0.6±0.7)、(0.6±0.5)mg.kg-1。S-DOX降低收缩压、舒张压和平均动脉压的作用均弱于rac-DOX和R-DOX(P<0.05),rac-DOX与R-DOX的降压作用差异无显著性(P>0.05)。rac-DOX在0.1～3.0mg.kg-1剂量范围内剂量依赖性抑制麻醉大鼠心率,而S-DOX和R-DOX仅在3.0mg.kg-1剂量时对心率有抑制作用。十二指肠给予S-DOX、R-DOX和rac-DOX均剂量依赖性降低麻醉大鼠膀胱排尿压,3种药物对排尿压的最大降低幅度分别为13.4%±5.7%、14.5%±11.0%和10.9%±7.6%,3者降低排尿压的作用差异无显著性(P>0.05)。与S-DOX相比,R-DOX可缩短排尿间隔并减少排尿量(P<0.05),而S-DOX和rac-DOX对排尿间隔和排尿量无影响。结论与R-DOX和rac-DOX相比,S-DOX保留了对麻醉大鼠膀胱排尿压的有利作用,减轻了对血压、心率和膀胱排尿间隔的不良影响。     

Role of vasopressin on excitatory amino acids mediated pressor responses in the periaqueductal gray area

In order to evaluate the role played by vasopressin on pressor responses elicited by stimulation of the periaqueductal gray (PAG) area by excitatory amino acids we carried out in vivo studies in genetically vasopressin deficient rats (Brattleboro). Microinjections of l-glutamic acid (glutamate, 0.6 to 60 nmol/rat) or N-methyl-d-aspartic acid (NMDA, 0.07 to 7 nmol/rat) into the PAG area of freely moving Brattleboro rats induced increases of arterial blood pressure values significantly lower than those obtained in Long Evans rats (control) (glutamate in Brattleboro rats: from +2±1 mmHg to 16±3 mmHg; glutamate in Long Evans rats: from +16±2 mmHg to +36±4 mmHg; NMDA in Brattleboro rats: from +5±2 mmHg to +34 ±8 mmHg; NMDA in Long Evans rats: from +18±7 mmHg to 80±9 mmHg; n=5). Similarly, in anaesthetized Brattleboro rats (urethane 1.2 g/kg i.p.) pressor responses to NMDA microinjections (0.7 nmol/rat) into the PAG area were significantly lower than in Long Evans rats (controls) (+15±3 mmHg vs +24±4 mmHg). In Long Evans rats NMDA injection also reversed blood pressure decrease induced by ganglionic blocker, hexamethonium and/or losartan (3 mg/kg i.v.), an AT1 receptor antagonist. In Brattleboro rats, NMDA injection did not reverse blood pressure decreases induced by hexamethonium (5 mg/kg i.v.). Moreover, hexamethonium induced blood pressure decrease was not reversed by acetylcholine injection (137 nmol/rat) into the PAG area of anaesthetized Long Evans rats, but if injected before hexamethonium, acetylcholine was able to increase blood pressure (+25±3 mmHg). Our results document: i) the importance of the PAG area in the control of cardiovascular system; ii) the involvement of excitatory amino acids in the neural control of vasopressin release; iii) the close relationship between glutamate and vasopressin in the central blood pressure regulation. Received: 1 April 1997 / Accepted: 2 February 1998     

Effect of intermedin/adrenomedullin-2 on venous tone in conscious rats

We investigated the effect of intermedin/adrenomedullin-2 (3 and 10 nmol/kg, i.v.), a member of the calcitonin gene-related peptide family, relative to the vehicle (0.9% NaCl) on mean circulatory filling pressure (index of venous tone) in conscious rats: intact (unblocked) or ganglionic blocked through treatment with mecamylamine (10 mg/kg, i.v.) and noradrenaline (4 μg/kg/min, i.v.). In intact rats, both doses of intermedin/adrenomedullin-2 reduced mean arterial pressure (−14±3, −30±3 mmHg), but did not alter mean circulatory filling pressure; the high dose also increased heart rate. In ganglionic-blocked rats, both doses decreased mean arterial pressure (−22±3, −46±5 mmHg) and the high dose also decreased mean circulatory filling pressure (−2.81±0.82 mmHg), but neither dose affected heart rate. The vehicle did not have any effects in any of the groups. In addition, intermedin/adrenomedullin-2 did not have any effect on blood volume in both intact and ganglion-blocked rats. The results show that intermedin/adrenomedullin-2 is a dilator of arterial resistance and capacitance vessels.     

The improvement of exercise performance by physical training is related to increased hypothalamic neuronal activation

The effects of physical training on hypothalamic activation after exercise and their relationship with heat dissipation were investigated. Following 8 weeks of physical training, trained (TR, n = 9) and untrained (UN, n = 8) Wistar rats were submitted to a regimen of incremental running until fatigue while body and tail temperatures were recorded. After exercise, hypothalamic c‐Fos immunohistochemistry analysis was performed. The workload, body‐heating rate, heat storage and body temperature threshold for cutaneous vasodilation were calculated. Physical training increased the number of c‐Fos immunoreactive neurons in the paraventricular, medial preoptic and median preoptic nucleus by 112%, 90% and 65% (P < 0.01) after exercise, respectively. In these hypothalamic regions, increased neuronal activation was directly associated with the increased workload performed by TR animals (P < 0.01). Moreover, a reduction of 0.6°C in the body temperature threshold for cutaneous vasodilation was shown by TR animals (P < 0.01). This reduction was possibly responsible for the lower body‐heating rate (0.019 ± 0.002°C/min, TR vs 0.030 ± 0.005°C/min, UN, P < 0.05) and the decreased ratio between heat storage and the workload performed by TR animals (18.18 ± 1.65 cal/kg, TR vs 31.38 ± 5.35 cal/kg, UN, P < 0.05). The data indicate that physical training enhances hypothalamic neuronal activation during exercise. This enhancement is the central adaptation relating to better physical performance, characterized by a lower ratio of heat stored to workload performed, due to improved heat dissipation.     

Injection of endothelin-1 into the raphe obscurus of rats induces depressor responses predominantly through endothelin ETA receptors

We used in vitro autoradiography to identify the endothelin-1 receptor subtype(s) in the nucleus raphe obscurus of rats. These studies showed dense binding of [¹²⁵I]PD151242 (for endothelin ET_A receptors), while tissues incubated with [¹²⁵I]BQ3020 (for endothelin ET_B receptors) had low binding. In addition, we examined the effects of the endothelin receptor antagonists FR 139317 (endothelin ET_A receptor-selective antagonist), SB 209670 (endothelin ET_A/ET_B receptor-non-selective antagonist) and BQ-788 (endothelin ET_B receptor-selective antagonist) on the blood pressure responses following administration of endothelin-1 into the nucleus raphe obscurus. The basal mean arterial blood pressure (MABP) of the rats was 110 ± 7 mmHg (n = 5). This was decreased in a dose-dependent manner by endothelin-1 (0.1, 1 and 10 pmol) microinjected into the nucleus raphe obscurus. This effect occurred within 1–6 s and recovered within 4 ± 1.2 min at a dose of 10 pmol. The doses of 0.1 pmol and 1 pmol ET-1 had responses which lasted 1 ± 0.4 min and 2 ± 0.2 min, respectively. Small decreases in heart rate accompanied the MAP responses to endothelin-1. For instance, the heart rate decreased by 16 ± 4 beats min^–1 after 10 pmol endothelin-1 (control, 366 ± 6 beats min^–1, n = 5). Decreases in blood pressure induced by endothelin-1 were greatly reduced by pre-administration to the nucleus raphe obscurus of FR139317 (5 nmol/rat) or SB209670 (3 nmol/rat; 97 ± 7% and 95 ± 6%, P < 0.01, n = 5, respectively), but were not affected by BQ-788 (50 nmol/rat; 8 ± 3%, P > 0.05, n = 5). The antagonists did not influence heart rate when injected to the nucleus raphe obscurus prior to endothelin-1. FR139317 (0.5 nmol) and SB209670 (0.3 nmol) had no effects on endothelin-induced changes in arterial blood pressure. Therefore, the autoradiographic study showed that there are binding sites for ET-1 within the nucleus raphe obscurus of rats, which are predominantly of ET_A type. The in vivo study showed that ET_A receptors are the predominant mediators of depressor responses induced by endothelin-1 injected into this nucleus. Received: 6 August 1998 / Accepted: 16 February 1999     

Oral simvastatin reduces the hypertensive response to air-jet stress

相似文献   

Enhanced external counterpulsation reduces indices of central blood pressure and myocardial oxygen demand in patients with left ventricular dysfunction

Enhanced external counterpulsation (EECP) therapy decreases angina episodes and improves quality of life in patients with left ventricular (LV) dysfunction. However, the underlying mechanisms relative to the benefits of EECP therapy in patients with LV dysfunction have not been fully elucidated. The purpose of this study was to investigate the effects of EECP on indices of central haemodynamics, aortic pressure wave reflection characteristics, and estimates of LV load and myocardial oxygen demand in patients with LV dysfunction. Patients with chronic stable angina and LV ejection fraction < 40% but > 30%, were randomized to either an EECP group (LV ejection fraction = 35.1 ± 4.6%; n = 10) or sham‐EECP group (LV ejection fraction = 34.3 ± 4.2%; n = 7). Pulse wave analysis of the central aortic pressure waveform and LV function were evaluated by applanation tonometry before and after 35 1‐h sessions of EECP or sham‐EECP. Enhanced external counterpulsation therapy was effective in reducing indices of LV wasted energy and myocardial oxygen demand by 25% and 19%, respectively. In addition, indices of coronary perfusion pressure and subendocardial perfusion were increased by 9% and 30%, respectively, after EECP. Our data indicate that EECP may be useful as adjuvant therapy for improving functional classification in heart failure patients through reductions in central blood pressure, aortic pulse pressure, wasted LV energy, and myocardial oxygen demand, which also suggests improvements in ventricular–vascular interactions.     

Renal vasodilation induced by hypernatraemia: Role of α‐adrenoceptors in the median preoptic nucleus

1. The renal vasodilation induced by infusion of hypertonic saline (HS) in anaesthetized rats has been shown to depend on the integrity of the median preoptic nucleus (MnPO), as well as noradrenergic afferents to this nucleus. In the present study, we sought to determine the role of α₁ and α₂‐adrenoceptors in the MnPO in cardiovascular responses induced by intravenous HS infusion (3 mol/L NaCl; 1.8 mL/kg, i.v., over 1 min). 2. Male Wistar rats (320–360 g) were anaesthetized with urethane (1.2 g/kg, i.v.) and instrumented for recording of mean arterial pressure (MAP), renal blood flow (RBF) and vascular conductance (RVC). In one experimental group, rats were injected with yohimbine, prazosin or saline (control) 20 min before HS infusion. In another experimental group, rats were injected with yohimbine or prazosin 20 min after HS infusion. 3. In control rats (n = 7), HS infusion 20 min after saline nanoinjection produced a transient hypertension. Ten minutes after HS infusion, RBF and RVC increased to 159 ± 14% and 145 ± 11% of baseline, respectively. Nanoinjection of the α₁‐adrenoceptor antagonist prazosin (0.25 mmol/L; n = 6) into the MnPO 20 min before HS infusion increased the HS‐induced pressor response. However, HS‐induced increases in RBF and RVC were significantly reduced (130 ± 11% and 105 ± 6% of baseline, respectively, 10 min after HS). Nanoinjection of the α₂‐adrenoceptor antagonist yohimbine (0.23 mmol/L; n = 5) into the MnPO 20 min before HS infusion increased the duration of the pressor response and reduced the increases in RBF and RVC induced by HS (117 ± 10% and 97 ± 11% of baseline, respectively, 10 min after HS). 4. We also observed that nanoinjections of the prazosin into the MnPO 60 min after HS infusion resulted in a gradual return of RBF and RVC to baseline values. However nanoinjection of yohimbine 60 min after HS failed to reduce renal vasodilatation induced by hypernatremia. 5. The results of the present study demonstrate that the integrity of adrenergic neurotransmission in the MnPO is essential for the renal vasodilation that follows acute increases in blood sodium concentration.     

Immunosuppression with mycophenolate mofetil attenuates the development of hypertension and albuminuria in deoxycorticosterone acetate‐salt hypertensive rats

1. The interplay between the immune and renin–angiotensin systems is emerging as a crucial factor in the development and progression of hypertension. The aim of the present study was to determine the involvement of immune cells in the hypertension and renal injury produced by a non‐angiotensin II‐dependent form of hypertension, namely deoxycorticosterone acetate (DOCA)‐salt‐induced hypertension, in rats. 2. Male Sprague‐Dawley rats underwent uninephrectomy and received either a sustained‐release pellet of DOCA s.c. and 0.9% NaCl (saline) to drink for 21 days or a placebo pellet and water to drink for 21 days. Additional groups of DOCA‐salt‐ and placebo‐treated rats were treated concurrently with the immune suppressant mycophenolate mofetil (MMF; 30 mg/kg per day). Rats were placed in metabolic cages for 24 h urine collection prior to and at weekly intervals during the 21 day experimental period. 3. Mycophenolate mofetil significantly attenuated the development of hypertension in DOCA‐salt rats compared with untreated DOCA‐salt hypertensive rats (mean arterial pressure by telemetry on Day 18 146 ± 7 vs 180 ± 3 mmHg, respectively; P < 0.001), as well as proteinuria (87 ± 27 vs 305 ± 63 mg/day, respectively, on Day 21) and albuminuria (51 ± 15 vs 247 ± 73 mg/day, respectively, on Day 21). Creatinine clearance was better preserved in MMF‐treated DOCA‐salt rats compared with untreated DOCA‐salt rats (0.74 ± 0.07 vs 0.49 ± 0.09 mL/min, respectively; P < 0.05), but was still significantly reduced compared with that in the placebo group (1.15 ± 0.12 mL/min; P < 0.05). Finally, MMF treatment significantly attenuated the DOCA‐salt‐induced rise in renal cortical T‐lymphocyte and macrophage infiltration (P < 0.05). 4. These data indicate that immune cells play a deleterious role in both the hypertension and renal injury associated with DOCA‐salt hypertension.