Different Effects of AT1 Receptor Antagonist and ETA Receptor Antagonist on Ischemia-Induced Norepinephrine Release in Rat Hearts

  title={Different Effects of AT1 Receptor Antagonist and ETA Receptor Antagonist on Ischemia-Induced Norepinephrine Release in Rat Hearts},
  author={Taiki Fukumoto and Masashi Tawa and Kento Kitada and Naoto Yamashita and Mamoru Ohkita and Tomio Okamura and Yasuo Matsumura},
  journal={Journal of Cardiovascular Pharmacology},
Abstract: Angiotensin type 1 receptor (AT1R) antagonist and endothelin type A receptor (ETAR) antagonist were compared as regards their effects on ischemia-induced exocytotic or carrier-mediated norepinephrine (NE) release from cardiac sympathetic nerve endings. According to the Langendorff technique, isolated rat hearts were subjected to 20-minute or 40-minute global ischemia followed by 30-minute reperfusion. Candesartan (selective AT1R antagonist) and ABT-627 (selective ETAR antagonist) were… Expand
4 Citations
Effects of the AT1 receptor blocker candesartan on myocardial ischemia/reperfusion in isolated rat hearts.
The addition of candesartan to a cardioplegic arrest protocol routinely performed during cardiac surgery did not provide a significant advantage in protection against ischemia-reperfusion injury compared with the administration of cardioleongic solution alone. Expand
Inhibition of infarction-induced sympathetic innervation with endothelin receptor antagonism via a PI3K/GSK-3β-dependent pathway
ETA receptor antagonism is a mediator to attenuate sympathetic hyperinnervation probably through restoration of PI3K/Akt/GSK-3β/ROS signaling pathway, a potential pharmacological target for arrhythmias after infarction. Expand
Endothelin receptor blockade ameliorates renal injury by inhibition of RhoA/Rho-kinase signalling in deoxycorticosterone acetate-salt hypertensive rats
Results indicate that DOCA-salt elevates renal endothelin-1 levels and RhoA activity via activation of mineralocorticoid receptor, resulting in renal fibrosis and proteinuria, probably through the inhibition of RHoA/ROCK activity and connective tissue growth factor expression. Expand
Angiotensin II receptor blockers following intravenous nicardipine administration to lower blood pressure in patients with hypertensive intracerebral hemorrhage: a prospective randomized study
Administration of ARBs following intravenous nicardipine effectively prevented BP from rising in Hich patients, however, whether BP should be strictly managed after 24 h of symptom onset should be addressed in future studies focusing not only on neurologic but also on cardiovascular and renal functions of HICH patients. Expand


Different Contributions of Endothelin-A and Endothelin-B Receptors in Postischemic Cardiac Dysfunction and Norepinephrine Overflow in Rat Hearts
ETA/NHE-mediated excessive NE overflow is contributive, at least in part, to postischemic cardiac dysfunction in rats, and exaggerated cardiac pathology under the above conditions is mediated by ETA receptor activation. Expand
Endothelin receptors, localized in sympathetic nerve terminals of the heart, modulate norepinephrine release and reperfusion arrhythmias
These studies provide the first evidence that both ETA and ETB receptors, located in the sympathetic nerve varicosities, modulate NE release, at least in part, in association with reperfusion arrhythmias. Expand
Angiotensin II Type 2 Receptor-Mediated Inhibition of Norepinephrine Release in Isolated Rat Hearts
Ang II seems to function as an inhibitory modulator of cardiac noradrenergic neurotransmission via AT2Rs and well-known AT1R-mediated stimulatory actions and may involve local bradykinin production, its B2 receptor activation, and NO as a downstream effector. Expand
The angiotensin II AT1-receptor antagonist candesartan improves functional recovery and reduces the no-reflow area in reperfused ischemic rat hearts.
It is demonstrated that candesartan reduces myocardial ischemia/reperfusion injury, thus indicating that endogenous cardiac angiotensin II is involved in the tissue injury after myocardia and reperfusion. Expand
Endothelin-1 inhibits the neuronal norepinephrine transporter in hearts of male rats.
Endothelin-1 potentiates norepinephrine (NE)-induced contractile responses and inhibits cardiac NE re-uptake but attenuates exocytotic NE release via ET(B), resulting in opposite effects on cardiac NE net release. Expand
Effects of the insurmountable angiotensin AT1 receptor antagonist candesartan and the surmountable antagonist losartan on ischemia/reperfusion injury in rat hearts.
The present results demonstrate that angiotensin AT1 receptor antagonists at equipotent concentrations could differ in their cardioprotective effects in hearts subjected to ischemia/reperfusion and it is suggested that the insurmountable AT1ceptor characteristics of candesartan could provide more persistentCardioprotection than the surmountable receptor characteristics of losartan. Expand
Effects of exogenous big endothelin-1 on postischemic cardiac dysfunction and norepinephrine overflow in rat hearts
It is suggested that exogenous big ET-1 has beneficial effects on ischemia/reperfusion-induced cardiac injury and it seems likely that bigET-1 is converted to Et-1, locally in the heart, and this ET- 1 preferentially binds to ETB receptors to exert its related beneficial actions. Expand
Selective endothelin a (ETA) receptor antagonist (BQ-123) reduces both myocardial infarct size and oxidant injury.
The most important finding of the present study is that the ET blockade reduced I/R-induced myocardial injury, and this decreased antioxidant enzymatic defense could result in aggravated oxidative damage in I-R group rat hearts. Expand
Coupling of angiotensin II AT1 receptors to neuronal NHE activity and carrier-mediated norepinephrine release in myocardial ischemia.
The results provide a link between AT(1)R and NHE in cSNE, which can exacerbate carrier-mediated NE release during protracted myocardial ischemia, and thereby facilitate the pathological release of NE associated with myocardia. Expand
Role of endogenous endothelin-1 in post-ischemic cardiac dysfunction and norepinephrine overflow in rat hearts.
Cardiac endothelin-1 production is enhanced by ischemia/reperfusion, and this endogenously increased endotheli-1 is involved in post-ischemic norepinephrine overflow and cardiac dysfunction via the activation of endothelins ET(A) receptors. Expand