Quinapril treatment and arterial smooth muscle responses in spontaneously hypertensive rats.

1 The effects of long-term angiotensin-converting enzyme inhibition with quinapril on arterial function were studied in spontaneously hypertensive rats, Wistar-Kyoto rats serving as normotensive controls. 2 Adult hypertensive animals were treated with quinapril (10 mg kg-1 day-1) for 15 weeks, which reduced their blood pressure and the concentrations of atrial natriuretic peptide in plasma and ventricular tissue to a level comparable with that in normotensive rats. 3 Responses of mesenteric arterial rings in vitro were examined at the end of the study. Compared with normotensive and untreated hypertensive rats, responses to noradrenaline were attenuated in hypertensive animals on quinapril, both force of contraction and sensitivity being reduced. Quinapril also attenuated maximal contractions but not sensitivity to potassium chloride. Nifedipine less effectively inhibited vascular contractions in normotensive and quinapril-treated than in untreated hypertensive rats. 4 Arterial relaxation responses by endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitrite, isoprenaline) mechanisms were similar in normotensive and quinapril-treated rats and more pronounced than in untreated hypertensive rats. 5 Cell membrane permeability to ions was evaluated by means of potassium-free solution-induced contractions of endothelium-denuded denervated arterial rings. These responses were comparable in normotensive and quinapril-treated rats and less marked than in untreated hypertensive rats. 6 Intracellular free calcium concentrations in platelets and lymphocytes, measured by the fluorescent indicator quin-2, were similar in normotensive and quinapril-treated rats and lower than in untreated hypertensive rats. 7 In conclusion, quinapril treatment improved relaxation responses and attenuated contractions in arterial smooth muscle of hypertensive rats. These changes may be explained by diminished cytosolic free calcium concentration, reduced cell membrane permeability, and alterations in dihydropyridine-sensitive calcium channels following long-term angiotensin-converting enzyme inhibition.     

醋柳黄酮对自发性高血压大鼠血管平滑肌细胞胞内游离钙浓度的影响

目的 :探讨醋柳黄酮 (TFH )、槲皮素(Que)、异鼠李素 (Isor)对自发性高血压大鼠 (SHR)及Wistar Kyoto大鼠 (WKY )血管平滑肌细胞(VSMC)胞内游离钙浓度 ([Ca2 + ]i)的影响。方法 :采用钙荧光探针Fluo 3/AM检测TFH及其主要单体Que和Isor,对培养的SHR及WKY的VSMC[Ca2 + ]i 水平在高钾 (K+ )、去甲肾上腺素 (NE)、血管紧张肽Ⅱ (AngⅡ )刺激下的改变 ,并与传统的钙拮抗剂维拉帕米进行对照研究。结果 :(1)TFH10 0mg·L- 1,Que 0 .1mol·L- 1,Isor 0 .1mol·L- 1对静息状态SHR的VSMC [Ca2 + ]i 有一定的抑制作用 (P <0 .0 1) ;而对WKY的VSMC [Ca2 + ]i无明显影响 (P >0 .0 5 )。 (2 )高K+ 使SHR[Ca2 + ]i 增加明显强于WKY(P <0 .0 1) ,TFH ,Que ,Isor明显抑制高K+ 去极化引起的SHR和WKY [Ca2 + ]i 升高 ,与维拉帕米作用相似 ,其对SHR [Ca2 + ]i升高的抑制作用明显强于对WKY(P <0 .0 1)。 (3)NE ,AngⅡ使SHR[Ca2 + ]i增加明显大于WKY (P <0 .0 1) ,TFH ,Que ,Isor对NE ,AngⅡ通过受体介导引起的SHR和WKY的VSMC[Ca2 + ]i 升高具有明显的抑制作用。 (4 )无细胞外钙存在下 ,TFH ,Que ,Isor对NE引起的SHR和WKY的VSMC[Ca2 + ]i 也具有一定程度的抑制效应 ,其对SHR[Ca2 + ]i 升高的抑制效应明显强于对WKY(P <0 .0 1)?     

Effects of calcium and potassium supplements on arterial tone in vitro in spontaneously hypertensive rats

1. Calcium and potassium intakes inversely correlate with blood pressure in experimental hypertension. Therefore, we examined the effects of calcium and potassium supplements alone and in combination on arterial tone in spontaneously hypertensive rats (SHR). Wistar-Kyoto (WKY) rats served as normotensive controls. Calcium and potassium contents in the control diet were both 1%, while those in supplemented chows were 3% and 3.5%, respectively. The sodium content of all diets was moderately elevated to 1.1%.
2. After 12 weeks of the study systolic blood pressures in SHR on high calcium and on high potassium diets were markedly lower (about 53 and 58 mmHg, respectively) than in hypertensive controls, while combined supplementation of these cations reduced blood pressure even further (about 69 mmHg).
3. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Both high calcium and high potassium diets improved the impaired relaxation to acetylcholine (ACh) in SHR, while the combination of these supplements completely normalized this response. Cyclo-oxygenase inhibition by diclofenac augmented the relaxation to ACh in hypertensive controls but not in the other groups. Nevertheless, enhanced endothelium-mediated dilatation was still observed in the presence of diclofenac and the nitric oxide synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME) in all supplemented groups. Interestingly, additional blockade of Ca²⁺-activated K⁺ channels by tetraethylammonium abolished the improved relaxation to ACh in SHR on high calcium and on high potassium, but distinct responses were still observed in WKY rats and SHR on the combined supplement.
4. When hyperpolarization of smooth muscle was prevented by precontraction of the preparations with 50 mM KCl, only marginal differences were observed in the diclofenac and L-NAME-resistant relaxations to ACh between the study groups. Finally, endothelium-independent vasorelaxations of noradrenaline-precontracted rings to nitroprusside, isoprenaline and cromakalim were comparably augmented by all supplements.
5. In conclusion, the vascular mechanisms underlying the antihypertensive effect of high calcium and high potassium diets during moderately elevated sodium intake in SHR may involve enhanced arterial hyperpolarization, increased smooth muscle sensitivity to nitric oxide and decreased production of vasoconstrictor prostanoids. The administration of these cations in combination was more effective than either of them alone in reducing blood pressure and restoring arterial tone.

     

硫化氢对肾血管性高血压大鼠动脉舒张功能的调节作用

目的探讨硫化氢(H2S)对肾血管性高血压模型大鼠血压及颈总动脉血管舒张功能的影响。方法采用"两肾一夹(2K1C)"法建立肾血管性高血压模型。大鼠随机分为假手术组、双肾一夹(2K1C)模型组、2K1C+Na HS(H2S供体)组及PPG(H2S代谢酶抑制剂)组。术前及术后每周测量1次大鼠尾动脉收缩压(SBP)。测定颈总动脉血管形态学指标(血管外周、壁厚、壁厚与外周径的比值),观察颈总动脉的ACh介导的内皮依赖性舒张作用;免疫组化检测颈总动脉一氧化氮合成酶(e NOS)、内皮素-1(ET-1)的表达。结果PPG组及2K1C组大鼠尾动脉血压与sham组比较明显升高(P<0.05);与模型组比较,2K1C+Na HS组血压明显降低,大鼠颈总动脉壁厚外径比减小,颈总动脉对ACh介导的内皮依赖性舒张效应增强,颈总动脉一氧化氮合成酶(e NOS)含量升高、ET-1含量降低。结论给予外源性的硫化氢供体可降低血压,缓解肾血管性高血压的形成,其作用可能与改善颈总动脉血管功能有关。     

Effects of the L- and N-type calcium channel blocker cilnidipine on growth of vascular smooth muscle cells from spontaneously hypertensive rats

Cultured vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) show exaggerated growth compared with cells from Wistar-Kyoto (WKY) rats. Calcium antagonists have recently been reported to have an in vivo antiproliferative effect on hypertensive cardiovascular organs. We investigated the effects of the calcium antagonist cilnidipine that blocks both L- and N-type calcium channels on the growth of VSMC from SHR. Cilnidipine (1 and 10 microM) significantly inhibited basal DNA synthesis in VSMC from both rat strains; the inhibition was significantly larger in VSMC from SHR than in cells from WKY rats, and was significantly greater than effects of nifedipine. Cilnidipine (1 microM) significantly inhibited serum-stimulated DNA synthesis in VSMC from both rat strains. The inhibition was more marked in VSMC from SHR than in cells from WKY rats. Angiotensin II, platelet-derived growth factor (PDGF)-AA, and phorbol-12-myristate-13-acetate dose-dependently increased DNA synthesis in VSMC from SHR but not in cells from WKY rats. Cilnidipine (1 microM) significantly suppressed this increase in DNA synthesis in VSMC from SHR. Expression of basic fibroblast growth factor (bFGF), transforming growth factor-beta1, and PDGF A-chain mRNAs was markedly greater in VSMC from SHR than in cells from WKY rats. Cilnidipine (1 microM) significantly inhibited the expression of TGF-beta1 mRNA in VSMC from SHR but not in cells from WKY rats. These findings suggest that cilnidipine exerts its antiproliferative effects through the inhibition of DNA synthesis induced by growth-promoting factors and by inhibiting the expression of TGF-beta1 mRNA in VSMC from SHR.     

Effect of nitric oxide on calcium-induced calcium release in coronary arterial smooth muscle.

The present study was designed to determine whether nitric oxide (NO)-induced reduction of [Ca(2+)](i) is associated with Ca(2+)-induced Ca(2+) release (CICR) in coronary arterial smooth muscle cells (CASMCs). Caffeine was used as a CICR activator to induce Ca(2+) release in these cells. The effects of NO donor, sodium nitroprusside (SNP), on caffeine-induced Ca(2+) release were examined in freshly dissociated bovine CASMCs using single cell fluorescence microscopic spectrometry. The effects of NO donor on caffeine-induced coronary vasoconstriction were examined by isometric tension recordings. Caffeine, a CICR or ryanodine receptor (RYR) activator, produced a rapid Ca(2+) release with a 330 nM increase in [Ca(2+)](i). Pretreatment of the CASMCs with SNP, CICR inhibitor tetracaine or RYR blocker ryanodine markedly decreased caffeine-induced Ca(2+) release. Addition of caffeine to the Ca(2+)-free bath solution produced a transient coronary vasoconstriction. SNP, tetracaine and ryanodine, but not guanylyl cyclase inhibitor, ODQ, significantly attenuated caffeine-induced vasoconstriction. These results suggest that CICR is functioning in CASMCs and participates in the vasoconstriction in response to caffeine-induced Ca(2+) release and that inhibition of CICR is of importance in mediating the vasodilator response of coronary arteries to NO.     

Changes of vascular smooth muscle reactivity in hypertensive rats

Mechanical responses produced by high potassium solution (high-K), norepinephrine (noradrenaline; NA) and phenylephrine (Phe) were examined in the thoracic aorta isolated from control (WKY) and spontaneously hypertensive rats (SHR). In the SHRs the tissues showed increased sensitivity to high potassium compared with those from the control rats. Mechanical removal of endothelium in tissues from the controls did not change the response. The effects produced by NA and Phe were also increased in tissues from SHRs. The amplitudes of contractions were enhanced after removal of the endothelium in tissues from the controls. The relaxation in response to endothelium-dependent vasodilators (acetylcholine and histamine) was significantly depressed in aortic rings from SHRs. Experiments using modified sandwich preparations suggest that the defect in the relaxant ability of vascular smooth muscle is coupled to a reduced functionality of the endothelium.     

糖尿病大鼠膀胱功能及平滑肌细胞内钙离子变化及意义

目的观察糖尿病神经源性膀胱尿动力学及逼尿肌细胞内钙离子变化,探讨其发病机制。方法建立糖尿病大鼠模型,正常大鼠作对照,测定不同糖尿病病程膀胱湿重、最大膀胱容量、膀胱顺应性及单个膀胱平滑肌细胞内钙离子浓度。结果糖尿病组大鼠膀胱湿重增加、最大膀胱容量、膀胱顺应性及平滑肌细胞内钙离子浓度较对照组高。结论糖尿病神经源性膀胱舒缩功能受损,为高顺应性膀胱,且随病程延长损害程度逐渐加重。平滑肌细胞内钙超载可能参与糖尿病后期逼尿肌的病理改变过程。     

Three levels of dietary calcium-effects on blood pressure and electrolyte balance in spontaneously hypertensive rats

Summary The effects of three levels of calcium intake on blood pressure (BP) and electrolyte balance were studied for 12 weeks in spontaneously hypertensive rats (SHR): the chow of the SHR-1 group contained 1.1% calcium, and that of the supplemented groups 2.1% (SHR-2) and 3.1% (SHR-3) calcium. Wistar-Kyoto rats on a 1.1% calcium diet (WKY-1) served as normotensive controls. After 10 and 12 weeks BP was significantly lower in both calcium-supplemented groups than in the SHR-1 group, the SHR-2 and SHR-3 groups not deviating from each other. Platelets and lymphocytes were used as experimental cell models to study the effects of the calcium diets on intracellular free calcium ([Ca²⁺]_i) level, which was measured by the fluorescent indicator quin-2. At the end of the study [Ca²⁺]_i was lower in both cell types in SHR-2 and SHR-3 than in SHR-1, the supplemented groups being comparable to each other. In platelets [Ca²⁺]_i still remained higher in the calcium-treated than the WKY-1 group, while in lymphocytes the levels were similar between SHR-2, SHR-3 and WKY-1. Plasma sodium, calcium and magnesium levels did not differ in the SHR groups, but plasma potassium was higher in both supplemented groups than in SHR-1. Plasma renin activity was comparable in SHR-1, SHR-2 and WKY-1, but was suppressed in the SHR-3 group. Creatinine clearance in the SHR-3 group was higher than in SHR-1 and SHR-2, but still remained lower than in WKY 1. High calcium intake was associated with a dose-dependent increase in urinary magnesium excretion, while the excretions of sodium and potassium were proportional to the intakes. The tissue Na⁺ :K⁺ ratio in abdominal aorta and tail artery was reduced in SHR-2,.but only a nonsignificant tendency was observed in SHR-3 when compared with the SHR-1 group.In summary, high calcium intake reduces [Ca²⁺]_i in both platelets and lymphocytes in SHR, suggesting that alterations in cellular calcium regulation may explain the BP-lowering effect of calcium supplementation. Elevation of dietary calcium level from 1.1% to 2.1% is associated with a lowering of the Na⁺ :K⁺ ratio in the arterial wall. A further increase in calcium content from 2.1% to 3.1% appears to have a favourable effect on renal function in SHR, but also aggravates magnesium loss into the urine. During the higher supplemented calcium intake, suppression of the renin-angiotensin system seems to be involved in the lowering of BP. Correspondence to H. Wuorela at the above address     

高血压大鼠和高血压患者血管平滑肌α肾上腺素受体的反应性增强作用

目的研究高血压状态下血管平滑肌α肾上腺素能受体的反应性增强作用。方法用敏感的离体血管张力描记技术记录大鼠肠系膜动脉和人大网膜动脉的张力，用实时定量的逆转录聚核酶链反应技术测定动脉平滑肌的mRNA水平，用动脉的器官培养方法研究α受体反应性增强的机制。结果自发性高血压大鼠(SHR)的肠系膜动脉环对去甲肾上腺素(NA)的反应性明显强于WKY大鼠，NA对SHR肠系膜动脉平滑肌的最大收缩(E_max)是WKY大鼠E_max的1.82倍；高血压患者大网膜动脉对NA的反应性明显高于非高血压患者，NA的量效曲线显著左移，pD₂值显著高于非高血压患者。SD大鼠肠系膜动脉的器官培养后对NA收缩反应增强，E_max增高，且培养后α₁受体的mRNA水平增高，而α₂受体的mRNA水平无明显变化。结论高血压状态下血管平滑肌α受体的反应性增强，提示α受体上调。     

硝苯地平和环匹阿尼酸对易卒中型肾性高血压大鼠血管平滑肌收缩功能的影响

观察了易卒中型肾性高血压大鼠（ＳＰＲＨＲ）主动脉环血管平滑肌在术后血压升高不同阶段收缩反应性．与假手术组相比，随着术后血压的升高，低浓度ＫＣｌ１０～２０μｍｏｌ·Ｌ－１使ＳＰＲＨＲ主动脉环的收缩反应明显增强；苯肾上腺素（Ｐｈｅ）在无钙Ｋｒｅｂｓ液中所致的收缩反应强度降低，而复钙后的收缩张力明显增强；ＳＰＲＨＲ主动脉环在无钙Ｋｒｅｂｓ液中温育１ｈ后，重新复钙后可致收缩反应且为硝苯地平（Ｎｉｆ）所抑制；肌浆网Ｃａ２＋泵抑制剂环匹阿尼酸（ＣＰＡ）在ＳＰＲＨＲ主动脉环上所致的持续收缩反应也明显强于对照并为Ｎｉｆ所阻断；连续给予Ｎｉｆ，卡托普利１８０±１１ｍｇ·ｋｇ－１·ｄ－１８ｗｋ后，ＳＰＲＨＲ的血压均明显下降．在术后１，４ｗｋ，Ｎｉｆ对部分ＳＰＲＨＲ主动脉环在无钙液中复钙所致的收缩反应并无抑制作用且可进一步引起收缩反应．结果表明，肾性高血压大鼠血管平滑肌收缩功能的高反应性与高血压状态下Ｃａ２＋转运的失调有关，不同高血压时期的血管平滑肌细胞膜上的Ｃａ２＋通道特性可能存在差异性．     

硝苯地平和环匹阿尼酸对易卒中型肾性高血压大鼠血管平滑肌收缩功能的影响

观察了易卒中型肾性高血压大鼠(SPRHR)主动脉环血管平滑肌在术?后血压升高不同阶段收缩反应性. 与假手术组相比，随着术后血压的升高，低浓度KCl 10～20 μmol·L^-1使SPRHR主动脉环的收缩反应明显增强；苯肾上腺素（Phe）在无钙Krebs液中所致的收缩反应强度降低，而复钙后的收缩张力明显增强；SPRHR主动脉环在无钙Krebs液中温育1 h后，重新复钙后可致收缩反应且为硝苯地平（Nif）所抑制；肌浆网Ca²⁺泵抑制剂环匹阿尼酸（CPA）在SPRHR主动脉环上所致的持续收缩反应也明显强于对照并为Nif所阻断；连续给予Nif，卡托普利180±11 mg·kg^-1·d^-1 8 wk后，SPRHR的血压均明显下降. 在术后1, 4 wk, Nif对部分SPRHR主动脉环在无钙液中复钙所致的收缩反应并无抑制作用且可进一步引起收缩反应. 结果表明，肾性高血压大鼠血管平滑肌收缩功能的高反应性与高血压状态下Ca²⁺转运的失调有关，不同高血压时期的血管平滑肌细胞膜上的Ca²⁺通道特性可能存在差异性.     

Effects of PPAR-gamma knock-down and hyperglycemia on insulin signaling in vascular smooth muscle cells from hypertensive rats

Peroxisome proliferator-activated receptor (PPAR)-gamma, a target in the treatment of diabetes, improves insulin sensitivity and exerts cardiovascular protective effects by mechanisms that are not completely elucidated. To investigate underlying molecular mechanisms responsible for PPAR-gamma-associated vascular insulin signaling in hypertension, we tested whether PPAR-gamma downregulation in vascular smooth muscle cells (VSMC) from WKY and SHRSP rats would decrease insulin signaling and glucose uptake and whether this response would be worsened by hyperglycemia to a greater extent in VSMC of hypertensive origin. Passaged mesenteric artery VSMC grown in euglycemic (5.5 mmol/L) or hyperglycemic media (25.0 mmol/L) were treated with PPAR-gamma-siRNA (5 nmol/L), PPAR-gamma antagonist (GW-9662, 10 micromol/L), or PPAR-gamma activator (rosiglitazone, 10 micromol/L) in the presence or absence of insulin (100 nmol/L). Immunoblotting revealed that hyperglycemia and PPAR-gamma inhibition significantly (P < 0.001) decreased insulin-stimulated insulin receptor (IR)-beta, Akt, and glycogen synthase kinase (GSK)-3beta phosphorylation, whereas phosphotyrosine phosphatase (PTP)-1B expression was increased in VSMC from both strains. These effects were more pronounced in SHRSP under hyperglycemia. Rosiglitazone tended to increase insulin-mediated IR-beta, Akt, and GSK-3beta phosphorylation in VSMC from both strains, whereas insulin-induced PTP-1B expression was reduced by hyperglycemia. Insulin-stimulated GLUT-4 expression and glucose transport were attenuated by hyperglycemia in both VSMC. These data suggest that PPAR-gamma inhibition results in decreased insulin signaling, particularly in SHR, in an IR-beta phosphorylation-dependent manner.     

埃他卡林对兔肺动脉平滑肌内皮细胞钙浓度的影响

目的观察埃他卡林(IPT)对内皮素1(ET-1)诱导培养的兔肺动脉平滑肌细胞(PASMC)增殖的影响,并探讨其作用机制。方法应用细胞培养、氚-胸腺嘧啶核苷([3H]-TdR)参入实验、Fluo-3和激光扫描共聚焦显微镜技术评价IPT对ET-1诱导的兔PASMC增殖及PASMC[Ca2+]i调节的作用。结果ET-1(10-7mol.L-1)使PASMC[3H]-TdR参入量增加146.8%,与对照组比较,差异有显著性(P<0.01);在相同条件下,加入ET-1的同时,分别向培养基中加入IPT10-7、10-6、10-5mol.L-1,细胞[3H]-TdR参入量分别下降(19.8±4.6)%、(41.2±9.5)%、(54.7±10.1)%,与ET-1组比较差异有显著性(P<0.01);对照组PASMC[Ca2+]i荧光强度和荧光光密度值较低;ET-1组中[Ca2+]i荧光光密度值明显增高,从73.7±10.1增加到143.8±28.2,两者比较差异有显著性(P<0.01);而IPT组细胞内荧光光密度值明显降低,仅从74.30±10.2增加到86.03±9.82,与ET-1组比较差异有显著性(P<0.01)。结论IPT可明显抑制ET-1诱导的兔PASMC增殖、DNA合成;减少钙通道的开放时间,抑制细胞内Ca2+浓度增加。     

Dietary calcium and magnesium supplements in spontaneously hypertensive rats and isolated arterial reactivity.

1. High calcium diet attenuates the development of hypertension but an associated undesirable effect is that Mg2+ loss to the urine is enhanced. Therefore, we studied the effects of high calcium diet alone and in combination with increased magnesium intake on blood pressure and arterial function. 2. Forty-eight young spontaneously hypertensive rats (SHR) were allocated into four groups, the dietary contents of Ca2+ and Mg2+ being: 1.1%, 0.2% (SHR); 2.5%, 0.2% (Ca-SHR); 2.5%, 0.8% (CaMg-SHR); and 1.1%, 0.8% (Mg-SHR), respectively. Development of hypertension was followed for 13 weeks, whereafter electrolyte balance, lymphocyte intracellular free calcium ([Ca2+]i), and mesenteric arterial responses in vitro were examined. Forty normotensive Wistar-Kyoto (WKY) rats were investigated in a similar manner. 3. Calcium supplementation comparably attenuated the development of Lypertension during normal and high magnesium intake in SHR, with an associated reduced lymphocyte [Ca2+]i and increased Mg2+ loss to the urine. 4. Endothelium-dependent arterial relaxation to acetylcholine was augmented in Ca-SHR and CaMg-SHR, while the relaxations to isoprenaline and the nitric oxide donor SIN-1 were similar in all SHR groups. Relaxation responses induced by the return of K+ to the organ bath upon precontractions in K(+)-free solution were used to evaluate the function of arterial Na+, K(+)-ATPase. The rate of potassium relaxation was similar in Ca-SHR and CaMg-SHR and faster than in untreated SHR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of ketamine on vascular smooth muscle function

1 In vitro studies were undertaken on rat aortic strips and portal vein segments to determine whether or not the amine-type anaesthetic, ketamine, can exert direct actions on vascular smooth muscle.

2 Ketamine was found to inhibit development of spontaneous mechanical activity and lower basal tension. This action took place with ketamine concentrations found in anaesthetic plasma concentrations, i.e., 1 × 10^-5 to 2 × 10^-4 M.

3 Ketamine (10^-5 to 10^-3 M) dose-dependently attenuated contractions induced by adrenaline, noradrenaline, angiotensin II, vasopressin and KCl. These inhibitory actions were observed with ketamine added either before or after the induced contractions.

4 Ca²⁺-induced contractions of K⁺-depolarized aortae and portal veins were also attenuated, dose-dependently, by ketamine.

5 In contrast to the above inhibitory actions, ketamine (2 × 10^-6 to 1 × 10^-4 M) was found to potentiate specifically 5-hydroxytryptamine(5-HT)-induced contractions of both aortic and venous smooth muscle. However, this was only observed if ketamine was added after 5-HT had initiated a contractile response.

6 All of the inhibitory, as well as 5-HT-potentiating, effects were completely, and almost immediately, reversed upon washing out the anaesthetic from the organ baths.

7 A variety of pharmacological antagonists failed to mimic or affect the inhibitory effects induced by ketamine.

8 These data suggest that rat plasma concentrations of ketamine commonly associated with induction of surgical anaesthesia can induce, directly, relaxation and contractile potentiation of vascular muscle.

9 These diverse findings may aid in explaining the well-known biphasic pressor actions of ketamine.