Inhibition of Endothelin-converting Enzyme Activity in the Rabbit Basilar Artery

Zimmermann, Michael; Jung, Carla S.; Raabe, Andreas; Spanehl, Oliver; Fach, Kilian; Seifert, Volker

doi:10.1097/00006123-200104000-00043

Cited by 3 publications

(2 citation statements)

References 55 publications

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“…Cells from diabetic rats were incubated (6-8 h) in 5 M of a peptide fragment of Big ET-1 (16-38) that has been shown to block ECE (32,51). The inhibition of ECE led to a marked and significant enhancement of both currents.…”

Section: Resultsmentioning

confidence: 99%

Role of PKC in autocrine regulation of rat ventricular K⁺currents by angiotensin and endothelin

Shimoni

Liu

2003

American Journal of Physiology-Heart and Circulatory Physiology

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Shimoni, Yakhin, and Xiu-Fang Liu. Role of PKC in autocrine regulation of rat ventricular K ϩ currents by angiotensin and endothelin. Am J Physiol Heart Circ Physiol 284: H1168-H1181, 2003 10.1152 10. /ajpheart.00748.2002 and sustained K ϩ currents were measured in isolated rat ventricular myocytes obtained from control, steptozotocin-induced (Type 1) diabetic, and hypothyroid rats. Both currents, attenuated by the endocrine abnormalities, were significantly augmented by in vitro incubation (Ͼ6 h) with the angiotensin-converting enzyme inhibitor quinapril or the angiotensin II (ANG II) receptor blocker saralasin. Western blots indicated a parallel increase in Kv4.2 and Kv1.2, channel proteins that underlie the transient and (part of the) sustained currents. Under diabetic and hypothyroid conditions, both currents were also augmented by an endothelin receptor blocker (PD142893) or by an endothelin-converting enzyme inhibitor. Kv4.2 density was also enhanced by PD142893. Incubation (Ͼ5 h) with the PKC inhibitor bisindolylmaleimide augmented both currents, whereas the PKC activator dioctanoyl-rac-glycerol (DiC8) prevented the augmentation of currents by quinapril. DiC8 also prevented the augmentation of Kv4.2 density by quinapril. Specific peptides that activate PKC translocation indicated that PKC-⑀ and not PKC-␦ is involved in ANG II action on these currents. In control myocytes, quinapril and PD142893 augmented the sustained late current but had no effect on peak current. It is concluded that an autocrine release of angiotensin and endothelin in diabetic and hypothyroid conditions attenuates K ϩ currents by suppressing the synthesis of some K ϩ channel proteins, with the effects mediated at least partially by PKC-⑀. diabetes; protein kinase C WE HAVE RECENTLY ESTABLISHED that an autocrine release of angiotensin II (ANG II) plays a central role in attenuating a transient and a sustained K ϩ current in single myocytes isolated from (Type 1) diabetic rats (45). The in vitro blockade of ANG II action or formation (for Ͼ5 h) augments both currents. This effect is blocked by cycloheximide, suggesting that new protein synthesis mediates current augmentation after removal of ANG II-related current inhibition.

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Section: Resultsmentioning

confidence: 99%

Role of PKC in autocrine regulation of rat ventricular K⁺currents by angiotensin and endothelin

Shimoni

Liu

2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…In a clinical study of intrathecal nicardipine, 39 vasospasm was not reversed except in arteries in the proximity of the catheter tip. Additionally, although intrathecally administered endothelin-1 antagonists showed potent antivasospastic effects in rat and rabbit SAH models, 26,48 this effect did not occur in canine or primate models. 7, 19 …”

Section: Discussionmentioning

confidence: 90%

Subarachnoid hemorrhage and the distribution of drugs delivered into the cerebrospinal fluid

Pluta

Butman

Schatlo

et al. 2009

JNS

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Object Investigators in experimental and clinical studies have used the intrathecal route to deliver drugs to prevent or treat vasospasm. However, a clot near an artery or arteries after subarachnoid hemorrhage (SAH) may hamper distribution and limit the effects of intrathecally delivered compounds. In a primate model of right middle cerebral artery (MCA) SAH, the authors examined the distribution of Isovue-M 300 and 3% Evans blue after infusion into the cisterna magna CSF. Methods Ten cynomolgus monkeys were assigned to SAH and sham SAH surgery groups (5 in each group). Monkeys received CSF injections as long as 28 days after SAH and were killed 3 hours after the contrast/Evans blue injection. The authors assessed the distribution of contrast material on serial CT within 2 hours after contrast injection and during autopsy within 3 hours after Evans blue staining. Results Computed tomography cisternographies showed no contrast in the vicinity of the right MCA (p < 0.05 compared with left); the distribution of contrast surrounding the entire right cerebral hemisphere was substantially reduced. Postmortem analysis demonstrated much less Evans blue staining of the right hemisphere surface compared with the left. Furthermore, the Evans blue dye did not penetrate into the right sylvian fissure, which occurred surrounding the left MCA. The authors observed the same pattern of changes and differences in contrast distribution between SAH and sham SAH animals and between the right and the left hemispheres on Days 1, 3, 7, 14, 21, and 28 after SAH. Conclusions Intrathecal drug distribution is substantially limited by SAH. Thus, when using intrathecal drug delivery after SAH, vasoactive drugs are unlikely to reach the arteries that are at the highest risk of delayed cerebral vasospasm.

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Sex differences in the modulation of K⁺ currents in diabetic rat cardiac myocytes

Shimoni

Liu

2003

The Journal of Physiology

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A transient (Ipeak) and a sustained (Isus) outward K+ current were measured, using whole‐cell voltage‐clamp methods, in isolated rat ventricular myocytes obtained by enzymatic dispersion. A comparison was made between male and female rats following induction of (insulin‐deficient) diabetes with streptozotocin (STZ). In control (non‐diabetic) rats, both currents were smaller in cells obtained from females, as compared to males (P < 0.005). However, whereas inducing diabetes in male rats significantly attenuated both Ipeak and Isus (P < 0.005), Ipeak was unchanged in female diabetic rats. Isus was significantly (P < 0.005) reduced, but the extent of reduction was smaller (P < 0.02) than in males. The formation of angiotensin II (ATII) or endothelin‐1 (ET‐1) was blocked using inhibitors of angiotensin‐converting enzyme (ACE) and endothelin‐converting enzyme (ECE), respectively. In cells from diabetic males both inhibitors significantly (P < 0.005) enhanced K+ currents. In contrast, no effect was observed in cells from female diabetic rats. However, in ovariectomized (Ovx) diabetic females the in vitro inhibition of ATII and ET‐1 formation augmented the two K+ currents, but not when oestradiol was administered in vivo prior to cell isolation. In cells from diabetic males, incubation with 100 nM 17β‐oestradiol significantly (P < 0.005) enhanced both Ipeak and Isus. This effect was blocked if ATII or ET‐1 was added to the medium. These results show that autocrine modulation of K+ currents by renin‐angiotensin and endothelin systems is attenuated or absent in female diabetic rats. Oestradiol plays a key role in reducing this modulation. These results may underlie some of the sex differences associated with development of cardiac arrhythmias.

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Inhibition of Endothelin-converting Enzyme Activity in the Rabbit Basilar Artery

Abstract: These results demonstrate that [D-Val22]big ET-1[16-38] and captopril act as highly potent ET-converting enzyme inhibitors, affecting big ET-1-induced contraction of the rabbit basilar artery.

Cited by 3 publications

References 55 publications

Role of PKC in autocrine regulation of rat ventricular K⁺currents by angiotensin and endothelin

Role of PKC in autocrine regulation of rat ventricular K⁺currents by angiotensin and endothelin

Subarachnoid hemorrhage and the distribution of drugs delivered into the cerebrospinal fluid

Sex differences in the modulation of K⁺ currents in diabetic rat cardiac myocytes

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Inhibition of Endothelin-converting Enzyme Activity in the Rabbit Basilar Artery

Abstract: These results demonstrate that [D-Val22]big ET-1[16-38] and captopril act as highly potent ET-converting enzyme inhibitors, affecting big ET-1-induced contraction of the rabbit basilar artery.

Cited by 3 publications

References 55 publications

Role of PKC in autocrine regulation of rat ventricular K+currents by angiotensin and endothelin

Role of PKC in autocrine regulation of rat ventricular K+currents by angiotensin and endothelin

Subarachnoid hemorrhage and the distribution of drugs delivered into the cerebrospinal fluid

Sex differences in the modulation of K+ currents in diabetic rat cardiac myocytes

Contact Info

Product

Resources

About

Role of PKC in autocrine regulation of rat ventricular K⁺currents by angiotensin and endothelin

Role of PKC in autocrine regulation of rat ventricular K⁺currents by angiotensin and endothelin

Sex differences in the modulation of K⁺ currents in diabetic rat cardiac myocytes