AT1-receptor blockade in experimental myocardial ischemia/reperfusion

The renin-angiotensin system is activated during myocardial ischemia, and angiotensin II is locally formed in ischemic hearts. At least four angiotensin II receptor subtypes have been identified, the AT1- and the AT2-receptor being the most prominent in the cardiovascular system. AT1-receptor blockade--like inhibition of the angiotensin-converting-enzyme (ACE)--limits infarct size, improves functional recovery following myocardial ischemia and attenuates ventricular remodeling, post-myocardial infarction and the resulting development of heart failure. The potential mechanisms responsible for the cardioprotection by AT1-receptor blockade remain to be elucidated in detail, but appear to involve AT2-receptor activation and--like ACE-inhibitors--bradykinin and prostaglandins. Combined treatment with ACE-inhibitors and AT1-receptor blockers has the potential to further reduce infarct size and improve ventricular remodeling over each monotherapy alone.     

Natriuretic and diuretic actions of a highly selective adenosine A1 receptor antagonist

The natriuretic and diuretic action of a highly selective adenosine A1 receptor (A1AdoR) antagonist, 1,3-dipropyl-8-[2-(5,6-epoxy)norbornyl]xanthine (CVT-124), was investigated in anesthetized rats. CVT-124 (0.1 to 1 mg/kg) caused dose-dependent increases in urine flow and fractional and absolute sodium excretion of by six- to 10-fold and, at 0.1 mg/kg, increased the GFR (1.6+/-0.1 to 2.5+/-0.2 ml/min; P<0.01). There were no changes in BP or heart rate. CVT-124 reduced absolute proximal reabsorption (26+/-3 to 20+/-2 nl/min; P<0.05) despite unchanged proximally measured, single-nephron GFR (SNGFR) (42+/-5 to 44+/-4 nl/min; NS) and thereby decreased fractional proximal reabsorption (60+/-3 to 46+/-4%; P<0.05). Despite increasing distal tubular fluid flow rate (5.4+/-0.7 to 9.7+/-0.9 nl/min; P<0.001), it reduced the proximal-distal difference in SNGFR (before: 9.4+/-1.0 versus during CVT-124: 4.6+/-1.5 nl/min; P<0.01), suggesting that it had blunted the effects of the macula densa on SNGFR. Direct measurements of maximal tubuloglomerular feedback (TGF) responses were made from proximal stop flow pressure (PSF) during orthograde loop perfusion from the proximal tubule with artificial tubular fluid at 40 nl/min. TGF was blunted by intravenous CVT-124 (0.5 mg/kg; deltaPSF with vehicle: 8.3+/-0.6 versus CVT-124: 6.5+/-0.3 mm Hg; n = 9; P<0.01). In conclusion, A1AdoR blockade reduces proximal reabsorption and uncouples it from glomerular filtration. It increases distal delivery of fluid yet does not activate a macula densa-dependent fall in SNGFR because it blunts the TGF response. Natriuresis accompanied by blockade of proximal glomerulotubular balance and TGF characterizes a new class of diuretic drugs.     

Effects of endothelin-1 and endothelin-1-receptor blockade on renal function in humans.

BACKGROUND: In patients with renal or cardiac failure, renal function may be endangered by elevated plasma concentrations of the vasoconstrictor endothelin-1 (ET-1). To mimic effects of pathologically increased plasma ET-1, we gave intravenous ET-1 in healthy subjects and examined whether simultaneous infusion of the ETA-receptor antagonist VML 588 would prevent the effects of ET-1 on the kidney. METHODS: Nine healthy men received on four separate days intravenous infusion of ET-1 (2.5 ng/kg/min) superimposed on vehicle (saline) or on VML 588 infusion (0.05, 0.20 and 0.40 mg/kg/h) in randomized order to assess the effects on renal function and renal haemodynamics. RESULTS: At resting plasma ET-1, infusion of VML 588 alone had no significant effects on renal function. Infusion of ET-1 alone decreased glomerular filtration rate by 11% and this reduction was not reversed by co-infusion of VML 588. ET-1 reduced renal blood flow by 35% and VML 588 reduced this decrease by one-third, in a dose-independent fashion. ET-1 increased the filtration fraction by 34% and VML 588 reduced this increase dose-independently by one-half. ET-1 increased renal vascular resistance by 59% and VML 588 reduced this increase dose-independently by one-half. Finally, ET-1 decreased sodium excretion by 58% and VML 588 reduced this decrease dose-independently by two-thirds. CONCLUSIONS: ET-1-induced reductions in renal function were partially but not completely prevented in a dose-independent manner by the ETA-receptor antagonist VML 588.     

Thromboxane A2-receptor blockade and prostacyclin in porcine Escherichia coli shock

Septic shock was induced by intravenous infusion of live Escherichia coli in pigs to investigate the influences on central hemodynamic, coagulation, and fibrinolytic reactions by a thromboxane A2 (TxA2)-receptor blocker (BM 13.177; n = 6) and a prostacyclin analogue (iloprost or ZK 36,374; n = 7). The early pulmonary vasoconstriction following E coli infusion was attenuated, but not abolished, by BM 13.177. Only minor effects were seen after pretreatment with iloprost. Neither drug had any major effect on the coagulation and fibrinolytic activation. These results confirm that TxA2 is an important, but not the only, mediator of early pulmonary vascular response in porcine septicemia and that neither TxA2 nor prostacyclin is of major importance for the hemostatic reactions in this shock model.     

Antiapoptotic effect of angiotensin-II type-1 receptor blockade in renal tubular cells of hyperoxaluric rats

In this study, we investigated the protective effect of losartan as an AT1 receptor antagonist by evaluating the expression of apoptosis-regulatory genes that contribute to the progressive damage in the renal tubules of hyperoxaluric rats. Rats were divided into 4 groups of 10 each; control (C), ethylene glycol (EG), ethylene glycol + losartan (EG + L) and Losartan (L). For 4 weeks 0.8% EG, as a precursor for oxalate, was administered to EG and EG + L and losartan (300 mg/l) was administered to groups EG + L and L. Urine and blood samples were collected for biochemical determination. Bcl-2, bax, caspase-3 and TGF-beta 1 antibodies were used for immunohistochemistry. Apoptosis was determined by TUNEL method. A marked increase in urinary oxalate levels of the rats in EG and EG + L groups was found. In the EG group a diffuse amount of oxalate crystals into the tubular lumina and interstitium in the cortex was observed. In the EG group GBM thickening, interstitial fibrosis and tubular atrophy with infiltration of mononuclear cell findings reduced in the EG + L group were presented as well. In the EG group, immunoreactivity of TGF-beta 1 was increased in glomeruli and tubuli. In the EG + L group, immunoreactivity of TGF-beta 1 was decreased compared to the EG group. Bax expression increased in the renal tubules of EG group and reduced in the EG + L group comparing to the control. In the EG + L group, the immunoreactivity of bcl-2 was increased in glomeruli. In EG + L treated group, number of caspase-3 immunopositive cells were decreased compared to all groups (P < 0.01). Apoptotic cells were increased in the EG-treated group compared to the other groups. Decreased apoptotic cell number was observed in the EG + L compared to the EG group (P < 0.01). Our findings suggest that losartan may provide a beneficial effect against tubulointerstitial damage and decrease renal tubular apoptosis caused by hyperoxaluria.     

鞘内注射腺苷A1受体激动剂对吗啡和可乐定镇痛作用的影响

目的 观察鞘内注射腺苷A1受体激动剂苯基异丙基腺苷(R-PIA)对吗啡和可乐定镇痛作用的影响.方法 健康雄性SD大鼠,鼠龄8～10周,体重250～300g,鞘内置管成功的85只大鼠随机分为17组,每组5只,对照组、R-PIA0.4组、R-PIA0.8组、R-PIA1.0组、茶碱组、吗啡2.0组、吗啡5.0组、可乐定2.0组、可乐定15.0组、R-PIA+吗啡2.0组、R-PIA+吗啡5.0组、R-PIA+可乐定2.0组、R-PIA+可乐定15.0组、可乐定+吗啡组均鞘内注射生理盐水,15min后分别注射生理盐水、R-PIA 0.4μg、R-PIA 0.8μg、R-PIA 1.0 μg、茶碱50 μg、吗啡2.0μg、吗啡5.0μg、可乐定2.0μg、可乐定15.0μg、R-PIA 0.4μg+吗啡2.0μg、R-PIA 0.4μg+吗啡5.0μg、R-PIA 0.4μg+可乐定2.0μg、R-PlA 0.4μg+可乐定15.0μg、可乐定2.0μg+吗啡2.0μg;R-PIA+吗啡+茶碱组、R-PIA+可乐定+茶碱组、可乐定+吗啡+茶碱组鞘内注射茶碱50μg,15 min后分别注射R-PIA 0.4μg+吗啡5.0μg、R-PIA 0.4μg+可乐定15.0μg、可乐定2.0μg+吗啡2.0μg,每次给药容积均为10μl.注药后5、10、20、30、40、60min时测定大鼠热辐射甩尾反应潜伏期(TFL),用最大效应百分比(MPE)[(注药后TFL-TFL的基础值)/(10.0-TFL的基础值)γ100%]评价镇痛效果.结果 高剂量R-PIA、吗啡、可乐定可升高MPE,R-PIA可增强吗啡、可乐定的镇痛作用,可被茶碱完全阻断,吗啡可增强可乐定的镇痛作用,可被茶碱部分阻断;可乐定可增强吗啡的镇痛作用.结论 大鼠鞘内注射R-PIA可增强吗啡和可乐定的镇痛作用,其机制可能与活化脊髓内腺苷受体有关.     

脑干网状结构内注射腺苷A1受体激动剂对大鼠的镇痛作用

目的 观察脑干网状结构内注射腺苷A1受体激动剂苯基异丙基腺苷(R-PIA)对大鼠的镇痛作用及其机制.方法 雄性SD大鼠,建立脑干网状结构内置管模型,置管后1周模型制备成功的60只大鼠随机分为12组(n=5)对照组、R-PIA0.5组、R-PIA1.0组、R-PIA2.0组、茶碱(腺苷受体阻滞剂)组、DPCPX(腺苷A1受体阻滞剂8-环戊二丙基黄嘌呤)组、格列本脲(ATP-敏感型钾通道阻滞剂)组、4-AP(电压依赖型钾通道阻滞剂4-氨基吡啶)组、R-PIA2.0+茶碱组、R-PIA2.0+DPCPX组、R-PIA2.0+格列本脲组、R-PIA2.0+4-AP组.前8组注射生理盐水后15 min分别注射生理盐水、R-PIA0.5μg、R-PIA 1.0μg、R-PIA 2.0μg、茶碱5.0μg、DPCPX 1.0μg、格列本脲5.0μg、4-AP 5.0μg;后4组注射R-PIA 2.0μg前15min分别注射茶碱5.0μg、DPCPX 1.0μg、格列本脲5.0μg、4-AP 5.0μg,每次给药容积均为0.3μl(用生理盐水稀释).用热辐射法测定注射R-PIA后5、15、30、45、60、90min大鼠甩尾反应潜伏期(TFL),痛阈以MPE[(给药后TFL-TFL的基础值)/(10.0-TFL的基础值)×100%]表示.结果 脑干网状结构内注射R-PIA 0.5～2.0μg有镇痛作用,且呈剂量依赖性,这种作用可被茶碱和DPCPX完全阻滞,被格列本脲和4-AP部分阻滞.结论 脑干网状结构内注射R-PIA对大鼠有一定的镇痛作用,通过作用腺苷A1受体,与开放ATP-敏感型和电压依赖型钾通道有关.     

Marked enhancement of anti-allodynic effect by combined intrathecal administration of the adenosine A1-receptor agonist R-phenylisopropyladenosine and morphine in a rat model of central pain

BACKGROUND: There is often no satisfactory treatment for chronic pain after spinal cord injury. We have previously reported that intrathecal (i.t.) administration of the adenosine A1-receptor agonist R-phenylisopropyl-adenosine (R-PIA) or the opioid morphine has anti-allodynic effects in a model of presumed chronic central pain after photochemically induced spinal cord injury in rats. In the present study, we set out to investigate the possible interaction between i.t. R-PIA and morphine in spinally injured rats. METHODS: Sprague-Dawley rats displaying allodynia-like behaviors to mechanical and cold stimuli after photochemically induced spinal cord injury with minor motor deficits were used. R-PIA and morphine, either alone or in combination, were administered i.t. through an implanted catheter to lumbar spinal cord. RESULTS: Cumulative doses of R-PIA or morphine dose-dependently reduced the mechanical allodynia-like behavior, with a threshold of 1 nmol and 1.5 nmol, respectively. When co-administrated, R-PIA and morphine produced marked suppression of mechanical allodynia at doses of 5 pmol and 7.5 pmol, respectively. The effect of i.t. co-administration of R-PIA and morphine on cold allodynia was comparable to i.t. R-PIA alone. The combination of R-PIA and morphine did not increase adverse effects such as motor deficits in comparison to either drug alone. CONCLUSION: These results demonstrate a supra-additive interaction between the adenosine A1-receptor agonist R-PIA and morphine to reduce mechanical allodynia-like behavior in rats with chronic spinal cord injury. The combination of R-PIA and morphine administered spinally may be superior to R-PIA or morphine alone for treating such pain.     

The effect of H2-receptor antagonist premedication on the duration of vecuronium-induced neuromuscular blockade in postpartum patients

The clinical duration of vecuronium was measured in two groups of postpartum patients undergoing elective tubal ligation. Ten patients received no premedication and ten others ranitidine 150 mg orally the morning of surgery. The mean duration of action of vecuronium was 57.2 +/- 9.9 min in the unmedicated patients and 54.0 +/- 12.9 min in the ranitidine treated patients. These values were significantly greater than the mean value for nonpregnant control patients (35.3 +/- 8.4 min) but indistinguishable from the mean value for cimetidine pretreated patients (63.0 +/- 17.6 min) reported previously. The combined results of the previous and present studies provide convincing evidence that the clinical duration of vecuronium-induced neuromuscular blockade is significantly longer in the postpartum patient and independent of cimetidine or ranitidine pretreatment.     

CRF-receptor 1 blockade attenuates acute posttraumatic hyperglycemia in rats

BACKGROUND: Hyperglycemia and insulin resistance after surgical stress are mediated by a complex neuroendocrine response. The present studies were undertaken to determine whether a corticotropin releasing factor (CRF)-receptor 1 (R1) antagonist, CP-154,526 (CP) could alter trauma-induced effects on blood glucose levels, insulin action on skeletal muscle, and dexamethasone-induced suppression of endogenous glucocorticoid secretion. MATERIALS AND METHODS: We used a standardized experimental model of small intestinal resection in the rat. Studies were performed 2 hours after surgery in four groups of rats (n = 24-48) given vehicle or 40 mg of CP i.p. 1 hour before surgical trauma or only anesthesia (controls). Measurements of (I) b-glucose and p-insulin, corticosterone, and ACTH; (II) glucose transport; (III) phosphatidylinositol 3-kinase (PI 3-K) activity in skeletal muscle; and (IV) the dexamethasone-suppression test were performed. RESULTS: Surgery resulted in hyperglycemia, reduced insulin-stimulated glucose transport, and a pathological dexamethasone-suppression test. B-glucose levels were attenuated in traumatized rats given CP compared to vehicle (P < 0.05). After surgery, p-corticosterone levels were moderately reduced by CP (P < 0.05) and p-ACTH unchanged by the drug. Glucose transport and PI 3-kinase activity as well as the dexamethasone-suppression test were unaffected by administration of CP. CONCLUSIONS: Hyperglycemia in response to small intestinal resection in the rat could be reduced but not inhibited by CRF-R1 blockade. We hypothesize that CRF action within the central nervous system can regulate the hyperglycemic response to surgical stress via mechanisms other than the pituitary-adrenal axis. Our results also indicate that the hypothalamic stress response after surgical stress is dependent on other factors apart from CRF.     

alpha 1-receptor blockade in therapy of benign prostatic hyperplasia syndrome. Correct dosing for optimal effectiveness

Four alpha 1-adrenoceptor antagonists are currently available for the medical treatment of lower urinary tract symptoms suggestive of benign prostatic obstruction in Germany: alfuzosin, doxazosin, tamsulosin, and terazosin. Indirect comparison based on randomized, placebo-controlled trials as well as several direct comparative studies have shown equal efficacy of all four drugs on urinary flow and symptom relief if suggested dosing regimens are applied. A dosing regimen below this recommendation should be restricted to those patients who have a proven satisfactory response to a lower dose.     

Characteristics of H2-receptor blockade in the canine mesenteric circulation.

Studies were conducted in anesthetized dogs to determine the effect of metiamide, an H₂-receptor antagonist to histamine, on the mesenteric vasodilatory response to histamine. Histamine alone (0.5 μg/kg-min) elicited a vasodilator response from the superior mesenteric artery consisting of two components: an early transient spike phase followed by a later stable and more sustained dilation of lesser amplitude. Metiamide, a dose-related manner, inhibited this late stable dilatory response and completely abolished it at a dose of 10^?4 mole/min. Histamine, on the other hand, in a dose of 1.25 μg/kg-min, overcame the inhibitory response to metiamide. These findings suggest that the mesenteric vasodilatory response to histamine is mediated through at least two distinct receptors. The ability of metiamide to inhibit the late stable vasodilation in a dose-related and surmountable fashion supports the hypothesis that this late phase is mediated predominantly through H₂ receptors and that the mechanism of blockade involves competitive inhibition.     

Attenuation of the tumor-promoting effect of surgery by spinal blockade in rats

BACKGROUND: The perioperative period is characterized by a state of immunosuppression, which was shown in animal studies to underlie the promotion of tumor metastasis by surgery. As this immunosuppression is partly ascribed to the neuroendocrine stress response, the authors hypothesized that spinal blockade, known to attenuate this response, may reduce the tumor-promoting effect of surgery. METHODS: Fischer-344 rats were subjected to a laparotomy during general halothane anesthesia alone or combined with either systemic morphine (10 mg/kg) or spinal block using bupivacaine (50 microg) with morphine (10 microg). Control groups were either anesthetized or undisturbed. Blood was drawn 5 h after surgery to assess number and activity of natural killer cells, or rats were inoculated intravenously with MADB106 adenocarcinoma cells, which metastasize only to the lungs. Metastatic development was assessed by quantifying lung retention of tumor cells 24 h after inoculation or by counting pulmonary metastases 3 weeks later. RESULTS: Laparotomy conducted during general anesthesia alone increased lung tumor retention up to 17-fold. The addition of spinal block reduced this effect by 70%. The number of metastases increased from 16.7 +/- 10.5 (mean +/- SD) in the control group to 37.2 +/- 24.4 after surgery and was reduced to 10.5 +/- 4.7 during spinal block. Systemic morphine also reduced the effects of surgery, but to a lesser degree. Natural killer cell activity was suppressed to a similar extent by surgery and by anesthesia alone. CONCLUSIONS: The addition of spinal blockade to general halothane anesthesia markedly attenuates the promotion of metastasis by surgery.     

Influence of combined neural blockade, H1- and H2-receptor and serotonin2-receptor blockade, indomethacin and tranexamic acid on leucocyte, temperature and acute-phase protein response to surgery

Body temperature, P-cortisol, P-glucose, P-transferrin, P-orosomucoid, P-IgM, hematocrit and total and differential leucocyte counts were investigated in 16 men undergoing inguinal herniotomy. The patients were randomized to epidural analgesia (n = 8) or epidural analgesia + assumed blockade of prostaglandin synthesis, blockade of receptors for histamine1, histamine2 and serotonin2, and inhibition of fibrinolysis with indomethacin, astemizole, ranitidine, ketanserin and tranexamic acid, respectively (n = 8). The rectal temperature and blood granulocyte counts rose significantly and similarly after surgery in both groups. Acute-phase protein (transferrin and orosomucoid) changes were also similar in both groups, as were P-cortisol and P-glucose, which did not increase in response to the neural blockade. Other factors than neural stimuli, prostaglandins, histamine, serotonin and activation of fibrinolysis are concluded to be effective in releasing postoperative leucocytosis, rise in body temperature and changes in acute-phase proteins.     

Natriuretic effect of calcium-channel blockers in hypertensives

This double-blind, randomized, crossover trial characterizes the acute natriuretic response to calcium-channel blockers (CCB) and investigates the role of hemodynamic and hormonal factors in mediating the natriuresis. Thirteen male subjects with essential hypertension received a single oral 20-mg dose of nifedipine or 120 mg of diltiazem. Renal functional and hemodynamic measurements were performed prior to and hourly for 4 hours following medication. Subjects then received these medications for 4 weeks at which time the above studies were repeated. Urinary sodium excretion increased within 60 minutes of CCB administration and the natriuresis was sustained for 4 hours. Cumulative sodium loss during the 4 hours of study was greater with nifedipine (43 +/- 12 mmol) than with diltiazem (18 +/- 6 mmol) (P less than 0.05). Despite natriuresis, urinary potassium excretion was decreased by both agents. Even though both drugs decreased the mean arterial pressure, inulin and paraaminohippurate (PAH) clearances were not altered. Plasma aldosterone concentrations decreased, plasma catecholamine concentrations increased, whereas plasma-renin activity was unchanged with both drugs. Body weight, glomerular filtration rate (GFR), renal plasma flow, plasma-renin activity, plasma aldosterone, and catecholamine concentrations were unchanged following 4 weeks of therapy. The acute natriuretic response after 4 weeks of therapy was similar to the response noted after the first dose. This study concludes that CCB are acutely natriuretic. Despite systemic hypotension, renal hemodynamics are unaltered during CCB therapy. Suppression of aldosterone as well as direct tubular effects of these drugs may mediate the natriuresis. Chronic therapy with CCB does not modify the acute natriuretic response to these agents.     

腺苷A1受体系统对兔脑缺血损伤的保护效应

目的　探讨腺苷A1 受体系统对兔脑缺血的保护作用。方法　家兔 2 4只随机分为对照组 (Ⅰ组 ,n =8)、缺血组 (Ⅱ组 ,n =8)和腺苷A1 受体激动药 +缺血组 (Ⅲ组 ,n =8) ,股动脉抽血至平均动脉压 35～ 40mmHg时 ,阻断双侧颈总动脉诱导脑缺血。观察术后第 3天海马CA1 区神经元密度。结果　 (1 )Ⅱ组神经元密度为 (76 50± 1 5 2 6)个 /毫米 ,显著低于Ⅰ组神经元密度 (2 0 8 1 3±1 1 0 8)个 /毫米 (P <0 0 5) ;而Ⅲ组神经元密度 [(1 30 78± 1 8 0 7)个 /毫米 ]明显高于Ⅱ组 (P <0 0 5)。结论　激活腺苷A1 受体系统能减轻脑缺血性损害     

H2-receptor blockade induces peptide YY and enteroglucagon-secreting gastric carcinoids in mastomys

Gastric carcinoid tumor formation has been reported with prolonged achlorhydria in both animals and human beings. The hypothesis in this study was that the ablation of parietal cell function in an animal (mastomys) genetically predisposed to gastric neuroendocrine neoplasia would promote and accelerate tumor formation. Loxtidine, an irreversible H2-receptor blocker, was administered at 1 mg/kg/day in drinking water for 4 months to young mastomys (n = 16). After 4 months of treatment, 14 of 16 animals had gastric carcinoids compared with 0 of 16 young control animals and 4 of 16 older control animals. Ultrastructurally, these tumors were characterized by the presence of neurosecretory granules. Serum gastrin levels were elevated (230 +/- 40 pmol/L) in loxtidine-treated animals compared with control animals (26 +/- 8 pmol/L) (p less than 0.05). In addition, both peptide YY (620 +/- 160 pmol/L) and enteroglucagon (500 +/- 147 pmol/L) were significantly elevated compared with control groups (p less than 0.05). Similarly, in tumor tissue, peptide YY (676 +/- 152 pmol/gm) and enteroglucagon (551 +/- 164 pmol/gm) were found in large quantities, whereas gastrin was undetectable. These observations provide substantial support for the possible pathophysiologic role of gut peptides, particularly gastrin, in the generation of endocrine neoplasia. The advent of endocrine tumors after inhibition of a gut secretory cell (parietal) may be of considerable significance in understanding the genesis of endocrine neoplasia. Whether the drug acts as a neoplastic promoter of enterochromaffin-like cells or the tumor development is related to elevation of peptides such as gastrin cannot be established in this study. Long-term H2-receptor blockade with new potent, irreversible agents as an alternative to surgery may have potential grave implications that require careful consideration.     

右美托咪定通过腺苷A1受体调节大鼠压力反射敏感性

目的观察腺苷A1受体在右美托咪定调节压力反射敏感性(baroreflex sensitivity,BRS)中的作用。方法健康成年雄性SD大鼠32只,体重240~280g,按随机数字表随机分为四组:对照组(C组)、选择性腺苷A1受体阻断剂组(P组)、右美托咪定组(D组)、选择性腺苷A1受体阻断剂+右美托咪定组(PD组),每组8只。C组泵注生理盐水40 ml·kg~(-1)·h~(-1)负荷量15 min,维持泵注10 ml·kg~(-1)·h~(-1);P组腹腔注射选择性腺苷A1受体阻断剂8-环戊基-1,3-二丙基黄嘌呤(DPCPX)1mg/kg,泵注同C组方案的生理盐水;D组右美托咪定负荷量100μg/kg,维持量100μg·kg~(-1)·h~(-1)持续泵注;PD组腹腔注射DPCPX 1mg/kg并泵注右美托咪定,泵注剂量同D组。采用苯肾上腺素升压法于泵注前(T_0)、泵注后60min(T_1)和泵注后120min(T_2)测定BRS。结果与T_0时比较,T_1和T_2时D组和PD组BRS明显升高(P0.05)。与C组和P组比较,T_1和T_2时D组和PD组BRS均明显升高(P0.05)。与D组比较,T_1和T_2时PD组BRS明显降低(P0.05)。结论右美托咪定可能通过腺苷A1受体增加大鼠BRS。