Eicosanoid-dependent and endothelium-independent oscillations of rat aorta.

We studied the role of endothelium and eicosanoids in rhythmic contractions of rat thoracic aorta. Spontaneous oscillations were observed in 35% of 385 endothelium-intact and in 46% of 22 endothelium-denuded aortic strips from normotensive Sprague-Dawley male rats. Vasoactive agents (norepinephrine, epinephrine, phenylephrine, isoproterenol, arachidonic acid, PGF2 alpha, serotonin, potassium, endothelin, atrial natriuretic factor and angiotensin II) induced rhythmic contractions in the majority of tissues. Rhythmic activity was also observed in aortic strips from adult female, pregnant and old male rats. Aortic oscillations were partially inhibited by indomethacin, ibuprofen and nordihydroguaiaretic acid (NDGA), and completely inhibited by indomethacin plus NDGA, nifedipine, low external calcium (less than 1 mM) and pretreatment with dexamethasone. Indomethacin, NDGA and arachidonic acid did not affect oscillations of the portal vein. Rhythmic contractions were observed in thoracic aortic strips from neonatal but not from adult rabbits. However, oscillations could be induced in strips of the mesenteric artery and terminal abdominal aorta of adult rabbits. Also, adult rabbit thoracic aortic strips exhibited oscillations when set up in close proximity of rat aorta. It is suggested that rhythmic contractions are physiological characteristics of many and perhaps all blood vessels and may play a role in blood flow and turbulence; the likely cause of these oscillations is the cyclic release of one or more eicosanoids.     

Increased expression of cyclooxygenase-2 mediates enhanced contraction to endothelin ETA receptor stimulation in endothelial nitric oxide synthase knockout mice

The aim of this study was to determine whether prolonged loss of NO activity, in endothelial NO synthase knockout (eNOS(-/-)) mice, influences endothelin (ET) ETA receptor-mediated smooth muscle contraction and, if so, to define the underlying mechanism(s). In isolated endothelium-denuded abdominal aortas, contractions to the selective ETA receptor agonist ET-1(1-31) were significantly increased in aortas from eNOS(-/-) compared with wild-type (WT) mice. In contrast, contractions to the alpha1-adrenergic agonist phenylephrine or the thromboxane (TX) A2 analog U-46619 were similar between eNOS(-/-) and WT mice. Immunofluorescent and Western blot analysis demonstrated that the aortic expression of ETA receptors was decreased in eNOS(-/-) compared with WT mice. Contractions evoked by ET-1(1-31), but not phenylephrine, were reduced by inhibition of cyclooxygenase-2 (COX-2) (indomethacin or celecoxib) or of TXA2/prostaglandin H2 receptors (SQ-29548). After COX inhibition, contractions to ET-1(1-31) were no longer increased and were actually decreased in eNOS(-/-) compared with WT aortas. Western blot analysis revealed that endothelium-denuded abdominal aortas express COX-2, but not COX-1, and that expression of COX-2 was significantly increased in eNOS(-/-) compared with WT mice. Contractions to the COX substrate arachidonic acid were also increased in eNOS(-/-) aortas. Furthermore, ET-1(1-31) but not phenylephrine stimulated production of the TXA2 metabolite TXB2, which was increased in eNOS(-/-) compared with WT aortas. Therefore, COX-2 plays a crucial and selective role in ETA-mediated smooth muscle contraction. Furthermore, COX-2 expression is increased in eNOS(-/-) mice, which overcomes a reduced expression of ETA receptors and enables a selective increase in contraction to ETA receptor stimulation.     

Chronic Ethanol Feeding Potentiates α1‐Adrenoceptor Responsiveness in SHR Aortas

Previous studies including ours demonstrated a hypotensive response to ethanol in spontaneously hypertensive rats (SHRs). In this study, we investigated whether this hypotensive effect of ethanol involves alterations in vascular α₁‐adrenergic receptor responsiveness. The contractile responses to the α₁‐receptor agonist phenylephrine were evaluated in aortic rings obtained from pair‐fed SHRs receiving liquid diet with or without ethanol (2.5% or 5%, w/v) for 3 months. The responses were measured in aortas with and without endothelium to determine the role of the endothelium in the observed responses. The liquid diet intake was similar in the control and ethanol groups throughout the study whereas the body weight was significantly reduced by ethanol. Cumulative addition of phenylephrine (1 × 10^?9–1 × 10^?4 M) caused concentration‐related contractile responses. These responses were significantly reduced after endothelium denudation suggesting a role for the endothelium in the modulation of α₁‐receptor responsiveness. Ethanol (2.5% and 5%) caused significant and concentration‐related increases in the contractile responses elicited by phenylephrine but not KCl. The maximum contraction (E_max) caused by phenylephrine in rings obtained from SHRs treated with 2.5% and 5% ethanol amounted to 413.6 ± 26.3 and 513.0 ± 46.7 mg tension/mg tissue, respectively, compared with 383.6 ± 35.2 mg tension/mg tissue in control rings. The enhancement of α₁ contractions by ethanol was virtually abolished in rings pretreated with the α₁‐receptor antagonist prazosin, suggesting upregulation of α₁‐receptors in aortas of ethanol‐fed rats. Endothelium denudation also abolished ethanol‐evoked increases in phenylephrine contractions. These findings suggest that chronic ethanol feeding upregulates aortic α₁‐receptors, which may be a consequence of chronic α₁‐receptor blockade by ethanol. The latter may account, at least in part, for the hypotensive response elicited by ethanol in SHRs.     

The Effect of Hydrogen Peroxide in Human Internal Thoracic Arteries: Role of Potassium Channels,Nitric Oxide and Cyclooxygenase Products

Introduction We investigated both the effect and the role(s) of potassium channels, nitric oxide (NO) and cyclooxygenase (COX) products in the effect of hydrogen peroxide (H₂O₂) in human internal thoracic artery (ITA) rings. Materials and methods Samples of redundant ITA obtained from patients undergoing a coronary artery bypass graft surgery were cut into 3 mm wide rings and suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. Results H₂O₂ (10⁻⁷–10⁻⁴ M) produced concentration-dependent relaxation responses in human ITA precontracted by phenylephrine. The relaxant responses to H₂O₂ did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of human ITA rings with superoxide dismutase (50 U/ml) did not affect the relaxant responses to H₂O₂, while 1,000 U/ml catalase caused a significant decrease. Incubation of endothelium-intact or endothelium-denuded human ITA rings with voltage-dependent potassium channel blocker 4-aminopyridine (5 mM) significantly inhibited the relaxant responses to H₂O₂. COX inhibitor indomethacin (10⁻⁵ M) also caused a significant inhibition. Incubation with ATP-dependent potassium channel blocker glibenclamide (10⁻⁶ M) or Ca²⁺-activated potassium channel blocker iberiotoxin (10⁻⁷ M) or NO synthase (NOS) blocker -nitro-l-arginine methyl ester (10⁻⁴ M) did not alter relaxant responses of ITA rings to H₂O₂. Conclusion The findings of the present study suggested that H₂O₂-induced relaxation responses in human ITA were neither dependant on the endothelium nor blocked by NOS inhibition but they rather seem to depend on the activation of voltage-dependent potassium channels and COX.     

Aging enhances contraction to thromboxane A2 in aorta from female senescence-accelerated mice

The time-course for aging-associated effects on vascular reactivity to U46619, a stable analogue of thromboxane A₂ (TXA₂), was studied in aorta from female senescence-accelerated mice-prone (SAMP8), a murine model of accelerated senescence. SAMP8 and senescence-accelerated mice-resistant (SAMR1) were divided into three groups: 3-, 6- and 10-month-old. Contractile curves to U46619 (10^?9 to 10^?6 M) were performed in aortic rings in the absence or in the presence of nitric oxide synthase (NOS) inhibitor N^G-nitro-l-arginine methyl ester (l-NAME; 10^?4 M) and/or cyclooxygenase (COX) inhibitor indomethacin (10^?5 M). Protein and gene expression for COX-1 and COX-2 were determined by immunofluorescence and real-time PCR, respectively. Maximal contraction to U46619 was markedly higher in SAMP8 at all ages. In SAMR1, increases were seen at 10 months, while SAMP8 displays augmented contraction at 6 months, which was further increased at 10 months. l-NAME enhanced U46619 contractions in both 6-month-old groups, although the increase was higher on vessels from SAMR1 at this age. Indomethacin equally increased U46619 contractions in both 3-month-old groups, suggesting the production of vasodilator prostaglandin in young animals. In contrast, at 6 and 10 months indomethacin decreased U46619 contractions in both groups, indicating an aging-associated swap to a release of contractile prostanoids in aorta. In conclusion, aging enhances contractile responses to TXA₂ in aorta from female mice by a mechanism involving a decrease of NO production and increased action of contractile prostanoids. This process occurs earlier in SAMP8 mice, establishing these mice as good model to study cardiovascular aging in a convenient and standard time-course.     

Vasodilator Effect of Phlomis bracteosa Constituents Is Mediated through Dual Endothelium-Dependent and Endothelium-Independent Pathways

This study describes the vasorelaxant potential of some pure compounds isolated from Phlomis bracteosa L.: marrubiin, phlomeoic acid, and two new constituents labeled as RA and RB. In rat thoracic aortic rings denuded of endothelium, marrubiin, phlomeoic acid, RA, and RB caused relaxation of high K⁺ (80 mM) and phenylephrine (1 μM)-induced contractions at the concentration range of 1.0–1000 μg/mL. Marrubiin, phlomeoic acid, RA, and RB concentration dependently (3.0–10 μg/mL) shifted the Ca⁺⁺ curves to the right obtained in Ca⁺⁺-free medium. The vasodilator effect of marrubiin, phlomeoic acid, RA, and RB was partially blocked by N_ω-nitro-L-arginine methyl ester in endothelium-intact aorta preparations. These results reveal that P. bracteosa constituents: marrubiin, phlomeoic acid, RA, and RB exhibit vasodilator action occurred via a combination of endothelium-independent Ca⁺⁺ antagonism and endothelium-dependent N_ω-nitro-L-arginine methyl ester-sensitive nitric oxide-modulating mechanism.     

Effects of long-term treatment with trandolapril on augmented vasoconstriction in rats with chronic heart failure

Background:

Despite the clinical relevance of angiotensin I-converting enzyme (ACE)inhibitors, their effects on impaired vascular function in patients and animals with chronic heart failure (CHF) have not been fully understood. This study was undertaken to determine whether long-term treatment with an ACE inhibitor improved the altered contractile properties of vessels from rats with CHF.

Methods and Results:

Twelve weeks after coronary artery ligation, the rats were sacrificed and the isometric tension development of thoracic aorta, pulmonary artery, and mesenteric artery with and without endothelium was examined. Contractile responses to norepinephrine and prostaglandin F₂α were augmented in endothelium-intact, but not in endothelium-denuded, thoracic aorta and pulmonary artery segments of the rat with CHF. The contractile response to angiotensin II was augmented in endothelium-denuded mesenteric artery segments of the rat with CHF, which was attenuated by indomethacin or diclofenac sodium but not by bunazosin. Trandolapril (3 mg/kg/d) was administered orally from the 2nd to 12th week after the operation. Treatment with trandolapril reversed the augmented contractile response of the rat with CHF to norepinephrine, prostaglandin F₂α, and angiotensin II almost to the levels in the sham-operated rat.

Conclusions:

The results demonstrate that an ACE inhibitor is capable of reversing altered vascular function in the rat with CHF, suggesting that vascular beds are possible sites of action for ACE inhibitors in the therapy for CHF.     

Stress Alone or associated with Ethanol Induces Prostanoid Release in Rat Aorta via α2-Adrenoceptor

Background

Stress and ethanol are both, independently, important cardiovascular risk factors.

Objective

To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats.

Methods

Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol. Concentration-responses curves to noradrenaline - in the absence and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were determined in thoracic aortas with and without endothelium. EC50 and maximum response (n=8-12) were compared using two-way ANOVA/Bonferroni method.

Results

Either stress or stress in association with ethanol consumption increased the noradrenaline maximum responses in intact aortas. This hyper-reactivity was eliminated by endothelium removal or by the presence of either indomethacin or yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol consumption did not alter the reactivity to noradrenaline. The phenylephrine responses in aortas both with and without endothelium also remained unaffected regardless of protocol.

Conclusion

Chronic stress increased rat aortic responses to noradrenaline. This effect is dependent upon the vascular endothelium and involves the release of vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared to neither influence noradrenaline responses in rat thoracic aorta, nor did it modify the increase of such responses observed as a consequence of stress exposure.     

Mechanism of superoxide anion-induced modulation of vascular tone

We investigated the effects of superoxide anions (O₂−) generated by xanthine (X) plus xanthine oxidase (XO) on isolated rabbit aorta suspended in Krebs-Ringer solution. Xanthine plus xanthine oxidase produced concentration-dependent contractions of rabbit aorta. Superoxide dismutase completely reversed the contractile response observed. Superoxide anion-induced contraction of rabbit aorta was totally abolished in preparations denuded of endothelium. The contractile effect was reduced by 56% by the cyclooxygenase inhibitor, indomethacin. The contractile effect was not affected by the angiotensin converting enzyme inhibitor, captopril. These results indicate that O ₁ ⁻ produces a contraction of the isolated rabbit aorta that is endothelium-dependent and is partly mediated by an arachidonic acid metabolite.     

Thiamine deficiency leads to reduced nitric oxide production and vascular dysfunction in rats

Background and aimsThiamine deficiency is a condition that is known to cause damage to the nervous and cardiovascular systems because it interferes with cellular metabolism. It is well known that the control of vascular function is highly dependent on the production of nitric oxide (NO) by NO synthases. Studies exploring the physiological relevance of NO signaling under conditions of thiamine deficiency are scarce. The present study sought to investigate whether chronic metabolic changes would cause alterations in vascular responsiveness.Methods and resultsBy removing thiamine from the diet, we observed a reduced acetylcholine-mediated relaxation and an increased phenylephrine-mediated vasoconstriction in the aortas containing functional endothelium. Removal of the endothelium or the pre-treatment of vessels with l-NAME restored the contractile responses to the level of controls. Conversely, indomethacin did not modify phenylephrine-mediated contractions. We also used carbon microsensors to continually measure NO production in situ while simultaneously measuring the vascular tone. The results revealed a significant decrease in NO production. Western blot analysis showed a decreased expression of the total eNOS in the thiamine-deficient aorta compared to the control. Concentration–response curves for phenylephrine indicated no difference between the control and deficient groups in the presence and absence of SOD or Tyron. The NO donor DEA-NONOate produced a concentration-dependent relaxation response in the endothelium-denuded vessels that did not differ between the control and thiamine-deficient rats.ConclusionThiamine deficiency modulates eNOS-dependent NO production, leading to a decreased vasorelaxation and an increased contractile response in the rat aorta.     

CYCLOOXYGENASE INHIBITION REDUCES BLOOD PRESSURE ELEVATION AND VASCULAR REACTIVITY DYSFUNCTION CAUSED BY INHIBITION OF NITRIC OXIDE SYNTHASE IN RATS

In the present study we investigated the role of cyclooxygenase (COX)-dependent vasoconstrictors in the hypertension and altered vascular reactivity following prolonged nitric oxide (NO) synthase inhibition. Male Wistar rats (250–270g) were divided into four groups and treated for 7 days with Placebo (control), L-NAME (48 mg/kg/day), indomethacin (4 mg/kg/day) and L-NAME in combination with indomethacin. L-NAME treatment induced arterial hypertension, in vitro aortic hyperresponsiveness to phenylephrine, impaired vasodilatory response to acetylcholine and no significant change in response to sodium nitroprusside. Indomethacin co-treatment partially prevented blood pressure elevation, restored responsiveness to phenylephrine and improved sensitivity to acetylcholine. Indomethacin treatment alone did not modify blood pressure and aortic vascular reactivity. Both enhanced phenylphrine-induced contraction and impaired acetylcholine-evoked vasodilation induced by acute NO synthase inhibition with L-NAME (10^?4M) in normal rat aortas were not modified by indomethacin (10^?5M). These results are consistent with the hypothesis that constricting factors, which arise from the COX pathway, contribute to hypertension and altered vascular reactivity following continued inhibition of NO synthase.     

Long-term inhibition of angiotensin converting enzyme suppresses calcium channel agonist-induced contraction of aorta in hypertensive rats

To elucidate functional changes in the vascular smooth muscle of spontaneously hypertensive rats (SHR) after chronic inhibition of angiotensin converting enzyme, we examined the contractile responses to different pharmacological interventions in the isolated aortas from SHR treated with a novel angiotensin converting enzyme inhibitor, CS-622 (10 mg/kg/day) for 20 weeks. In normal K+ medium, a marked contraction was elicited by increasing Ca2+ concentration from 0 to 3 mM in aortas from a control group of SHR, but not in aortas from SHR treated with CS-622. In 60 mM K+ medium, however, the sensitivity of aorta to Ca2+ was almost the same in the two groups. A calcium channel activator, CGP-28392 (10(-7) to 10(-6) M), induced a marked contraction in the aortas from control SHR, but not in the aortas from CS-622-treated SHR. When slightly depolarized in 10 or 12 mM K+ solution, the aortas from CS-622-treated SHR contracted in response to CGP-28392. The aortic sensitivity to KCl contraction was much lower in CS-622-treated SHR than in untreated SHR, whereas the sensitivity to phenylephrine contraction was little different in the two groups. These contractile profiles of aortas from CS-622-treated SHR were very similar to those from normotensive Wistar-Kyoto rats but not to those from hydralazine-treated SHR. These data suggest that contractions due to Ca2+ through voltage-dependent calcium channels are exaggerated in SHR aorta and that long-term treatment with angiotensin converting enzyme inhibitor suppresses the abnormal contractility of SHR vascular smooth muscle, probably through alterations of voltage-related functions of calcium channels.     

Chronic ethanol feeding potentiates alpha1-adrenoceptor responsiveness in SHR aortas

Previous studies including ours demonstrated a hypotensive response to ethanol in spontaneously hypertensive rats (SHRs). In this study, we investigated whether this hypotensive effect of ethanol involves alterations in vascular alpha1-adrenergic receptor responsiveness. The contractile responses to the alpha1-receptor agonist phenylephrine were evaluated in aortic rings obtained from pair-fed SHRs receiving liquid diet with or without ethanol (2.5% or 5%, w/v) for 3 months. The responses were measured in aortas with and without endothelium to determine the role of the endothelium in the observed responses. The liquid diet intake was similar in the control and ethanol groups throughout the study whereas the body weight was significantly reduced by ethanol. Cumulative addition of phenylephrine (1 x 10(-9)-1 x 10(-4) M) caused concentration-related contractile responses. These responses were significantly reduced after endothelium denudation suggesting a role for the endothelium in the modulation of alpha1-receptor responsiveness. Ethanol (2.5% and 5%) caused significant and concentration-related increases in the contractile responses elicited by phenylephrine but not KCl. The maximum contraction (Emax) caused by phenylephrine in rings obtained from SHRs treated with 2.5% and 5% ethanol amounted to 413.6 +/- 26.3 and 513.0 +/- 46.7 mg tension/mg tissue, respectively, compared with 383.6 +/- 35.2 mg tension/mg tissue in control rings. The enhancement of alpha1 contractions by ethanol was virtually abolished in rings pretreated with the alpha1-receptor antagonist prazosin, suggesting upregulation of alpha1-receptors in aortas of ethanol-fed rats. Endothelium denudation also abolished ethanol-evoked increases in phenylephrine contractions. These findings suggest that chronic ethanol feeding upregulates aortic alpha1-receptors, which may be a consequence of chronic alpha1-receptor blockade by ethanol. The latter may account, at least in part, for the hypotensive response elicited by ethanol in SHRs.     

Cysteinyl leukotrienes are involved in angiotensin II-induced contraction of aorta from spontaneously hypertensive rats

OBJECTIVE: Non specific lipoxygenase inhibitors have been reported to reduce the in vitro constrictor response and the in vivo pressor effect of angiotensin II in rats. The aim of this study was to assess the role of cysteinyl leukotrienes, in the vascular response to angiotensin II in spontaneously hypertensive rats (SHR). METHODS: Rings of thoracic aorta from SHR and normotensive Wistar-Kyoto rats (WKY) were compared in terms of contractile responses and release of cysteinyl leukotrienes in response to angiotensin II. RESULTS: Pretreatment with the specific 5-lipoxygenase inhibitor AA861 10 microM reduced the efficacy of angiotensin II in intact and endothelium-denuded aorta from SHR (% inhibition vs. control: 65+/-12.6% with endothelium (n=6), P<0.05; 43+/-7.2% without endothelium (n=6), P<0.05) but not in aorta from WKY. In addition, in aorta from SHR, the CysLT(1) receptor antagonist MK571 1 microM reduced by 55+/-6.1% (n=6, P<0.05) the contractile effects of angiotensin II in rings with endothelium but not in endothelium-denuded rings. Angiotensin II induced a 8.6+/-2.1-fold increase in cysteinyl leukotriene production in aorta rings from SHR with endothelium which was prevented by the AT(1) receptor antagonist losartan 1 microM but not by the AT(2) receptor antagonist PD123319 0.1 microM. In aorta rings from WKY, cysteinyl leukotriene production remained unchanged after exposition to angiotensin II. The cysteinyl leukotrienes (up to 0.1 microM) induced contractions in aorta rings from SHR but not from WKY. CONCLUSIONS: These data suggest that cysteinyl leukotrienes, acting at least in part on endothelial CysLT(1) receptors, are involved in the contractile response to angiotensin II in isolated aorta from SHR but not from WKY.     

Calcium Supplementation Is Associated With Endothelium Dependent Attenuation of Vascular Smooth Muscle Reactivity in Normotensive Pregnant and Nonpregnant Rats

The study tests the hypothesis that the blood pressure lowering effect of a high calcium diet is mediated through attenuation of vascular reactivity and examined the mechanisms involved in both normotensive pregnant and nonpregnant rats. The contractile responses of aortic rings of Wistar rats fed on high (1.7%, 2.1%) and normal (0.9%) calcium diets to phenylephrine, angiotensin II, KCl, and CaCl₂ were studied. The relaxations to acetylcholine and potassium chloride, as well as the effects of endothelial denudation, pretreatment with indomethacin (10⁻⁶ mol/L), methylene blue (10⁻⁶ mol/L), and calcium free solution on the responses to phenylephrine were also examined.In both pregnant and nonpregnant rats, the contractile responses of aortic rings of animals fed a high calcium diet to all the agents were significantly attenuated, compared with those of controls. After endothelial denudation, or treatment with methylene blue, but not with indomethacin, the responses of the rings to phenylephrine were enhanced and not different from similarly treated rings from rats on a normal calcium diet. There was no difference in the contractile responses to phenylpehrine in calcium free solution. The relaxation to acetylcholine, but not to potassium chloride, was enhanced in rings from rats on a high calcium diet. The diminution in reactivity was not associated with corresponding changes in sensitivity of the tissues.It is concluded that in normotensive rats a high calcium diet is associated with diminished vascular smooth muscle reactivity that is endothelium dependent, and involves increased stimulation of the nitric oxide–guanylate cyclase pathway but not of the sodium–potassium ATPase or prostacyclin.     

Effects of nesfatin-1 on atrial contractility and thoracic aorta reactivity in male rats

Background: This study aimed to examine the effects of nesfatin-1 on thoracic aorta vasoreactivity and to investigate the inotropic and chronotropic effects of nesfatin-1 on the spontaneous contractions of the isolated rat atria.

Methods: Isolated right atria and thoracic aorta were used in organ baths. The reactivity of the thoracic aorta was evaluated by potassium chloride (KCl), phenylephrine (Phe), acetylcholine (ACh), and sodium nitroprusside (SNP). The effects of nesfatin-1 on the spontaneous contractions of the rat atria were also examined.

Results: Nesfatin-1 (0.1–100 ng/ml) produced a concentration-dependent relaxation response in rat thoracic aorta. The relaxant responses to nesfatin-1 were inhibited by the removal of endothelium, NO synthase blocker N-nitro-L-arginine methyl ester (L-NAME, 10^?4 M), and soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10^–5 M). Nesfatin-1 (10 ng/ml, 30 min) increased the relaxation responses to either ACh or SNP, and the contractile response to both Phe and KCl did not significantly change in the arteries that were incubated with nesfatin-1 compared with the controls. The thoracic aorta contractions induced by the stepwise addition of Ca²⁺ to a high KCl solution with no Ca²⁺ were not significantly changed by nesfatin-1. Under calcium-free conditions, the contractions of the thoracic aorta rings incubated with nesfatin-1 in response to Phe were not significantly lower than those of the rings from the control rats. Nesfatin-1 showed positive inotropic and chronotropic effects on rat atria.

Conclusion: Nesfatin-1 significantly changed the vascular responsiveness in rat thoracic aorta and produced positive inotropic and chronotropic effects on rat atria.     

蜂毒肽对大鼠主动脉收缩的作用及与钙内流的关系

为探讨蜂毒肽对心血管系统的作用机理,利用离体大鼠主动脉收缩实验及血管平滑肌细胞＾４５Ｃａ内流定量测定方法,观察了蜂毒肽对血管平滑肌的影响。结果发现：蜂毒肽不影响内皮完整主动脉由苯肾上腺素引起的快速收缩,但可溶度依赖地抑制持续收缩;蜂毒肽对去内皮主动脉环由苯肾上腺素引起的收缩无作用;蜂毒肽对内皮完整主动脉未能产生收缩反应,但可使去内皮动脉环产生收缩和＾４５Ｃａ内流增加,卡手普利和苄普地尔能部分拮抗这     

Role of endothelium-derived prostanoid in angiotensin-induced vasoconstriction

To test the hypothesis that prostanoids contribute to angiotensin II-induced vascular contraction, we compared the effect of angiotensin II on isometric tension development by rings of descending thoracic aorta bathed in Krebs' bicarbonate buffer with and without indomethacin (10 microM) to inhibit cyclooxygenase, CGS13080 (10 microM) to inhibit thromboxane A2 synthesis, or SQ29548 (1 microM) to block thromboxane A2/prostaglandin endoperoxide receptors. The comparisons were made in rings of aorta taken from normotensive rats and from rats with aortic coarctation-induced hypertension at 12 days and 90-113 days after coarctation. These rings released thromboxane B2, which was found to be endothelium dependent, increased in hypertensive rats, and stimulated by angiotensin II (10(-6) M) in normotensive rats and in hypertensive rats at 12 days after coarctation. The angiotensin II (10(-6) to 10(-5)M)-induced contraction of aortic rings was increased by about 30% at 12 days after coarctation and decreased at 90-113 days after coarctation. Removal of the endothelium increased the contractile effect of angiotensin II (10(-6) M) in aortic rings of normotensive rats and hypertensive rats at 90-113 days after coarctation but decreased the effect in aortic rings of hypertensive rats at 12 days after coarctation. In rats at 12 days after coarctation, the angiotensin II (10(-6) M)-induced contraction of aortic rings with endothelium was attenuated by indomethacin and SQ29548 but not by CGS13080. These data suggest that a prostanoid-mediated and endothelium-dependent mechanism of vasoconstriction contributes to the constrictor effect of angiotensin II in aortic rings of rats in the early phase of aortic coarctation-induced hypertension.     

Endothelium-derived contracting factor released by serotonin in the aorta of the spontaneously hypertensive rat.

Contractions to serotonin are augmented in aortas with endothelium from spontaneously hypertensive rats (SHR) compared to normotensive controls (WKY). Experiments were designed to determine whether this is due to the release of a vasoconstrictor prostanoid from the endothelium. Rings of aortas with and without endothelium were taken from SHR and WKY and suspended in organ chambers for isometric tension recording. Contractions to serotonin were similar in rings without endothelium from both strains. The presence of the endothelium reduced the contractions to all concentrations of serotonin in the WKY; in the SHR the endothelium inhibited only the response to lower concentrations of serotonin. Indomethacin (or meclofenamate) reduced the contractions to high concentrations of serotonin only in rings from SHR with endothelium; it did not affect the response in SHR rings without endothelium or in rings from WKY (with and without endothelium). The endothelium inhibited contractions to norepinephrine only in the presence of indomethacin in both strains. These experiments suggest that serotonin stimulates the release of vasoconstrictor prostanoids from the endothelium of the SHR but not from the WKY aorta. Norepinephrine may release endothelium-derived contracting factor(s) in both strains.     

Effects of Taurine on Aortic Rings Isolated from Fructose-fed Insulin Resistance Sprague–Dawley Rat are Changed

Purpose  To observe and compare the effect of taurine on contractions of aortic rings isolated from normal (NC) and insulin resistance (IR) Sprague–Dawley rats, and to explore its underlying mechanism(s). Methods  The IR animal model was made by feeding rats with high fructose diet for 8 weeks. Aortic rings were isolated and suspended in a tissue bath, and tensions were recorded isometrically. The effects of taurine on provoked contractions of the rings were assessed in absence or presence of different potassium channel or NO-synthase inhibitors. Results  Taurine (20–80 mM) concentration-dependently relaxed precontractions induced by KCl (30 mM) and phenylephrine (1 μM) in NC rings, but enhanced the precontractions in IR rings. Denudation of the endothelium and pretreatment with N ^G-nitro-l-arginine methylester ester (0.1 mM) reversed the contraction enhancement of taurine to relaxation in IR rings. Tetraethylammonium (10 mM) nearly abolished taurine-induced relaxation of NC rings, and augmented taurine-induced contraction enhancement in IR rings. Iberiotoxin (100 nM) only augmented the contraction enhancement in IR rings. 4-Aminopyridine (1 mM), glibenclamide (10 μM) and indomethacin (10 μM) had no influence on the effect of taurine in both NC and IR rings. Conclusion  Taurine enhances contractions in IR aortic rings but relaxes the contractions in normal rat aortic ring; the enhancement is endothelium-dependent and the relaxation is endothelium-independent. TEA-sensitive K⁺ channel may be involved in these actions; BK_Ca channel dysfunction and endothelium-derived substances may be related to the contraction enhancement induced by taurine in IR aorta.