Effect of disease states on α1 -adrenoceptor binding and signal transduction parameters in isolated perfused heart: quantification by pharmacokinetic-pharmacodynamic modelling

2013 ◽  
Vol 66 (5) ◽  
pp. 668-676
Author(s):  
Michael Weiss ◽  
Petra Arendt ◽  
Rana Hassna
Keyword(s):  
Signal Transduction ◽  
Isolated Perfused Heart ◽  
Perfused Heart ◽  
Disease States ◽  
Pharmacodynamic Modelling

EFFECTS OF ENERGY AND PROTEIN RESTRICTION ON ACETYLCHOLINE SENSITIVITY OF RAT ISOLATED PERFUSED HEART

1985 ◽  
Vol 12 (6) ◽  
pp. 573-576 ◽  
Author(s):  
B. V. Venkataraman ◽  
P. S. Shetty ◽  
Thangam Joseph ◽  
H. Mohamed Arifullah ◽  
P. M. Stephen
Keyword(s):  
Protein Restriction ◽  
Isolated Perfused Heart ◽  
Perfused Heart ◽  
Acetylcholine Sensitivity

Abstract 292: The Role of the ATF6 Branch of the ER Stress Response in the Endocrine Heart

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Erik A Blackwood ◽  
Christopher C Glembotski
Keyword(s):  
Stress Response ◽  
Er Stress ◽  
Knockout Mice ◽  
Ex Vivo ◽  
Proteolytic Cleavage ◽  
Isolated Perfused Heart ◽  
Wild Type ◽  
Atrial Myocytes ◽  
Perfused Heart ◽  
Er Stress Response

Rationale: Atrial natriuretic peptide (ANP) is stored in the heart in large dense core granules of atrial myocytes as a biologically inactive precursor, pro-ANP. Hemodynamic stress and atrial stretch stimulate coordinate secretion and proteolytic cleavage of pro-ANP to its bioactive form, ANP, which promotes renal salt excretion and vasodilation, which, together contribute to decreasing blood pressure. While the ATF6 branch of the ER stress response has been studied in ventricular tissue mouse models of myocardial ischemia and pathological hypertrophy, roles for ATF6 and ER stress on the endocrine function of atrial myocytes have not been studied. Objective/Methods: To address this gap in our knowledge, we knocked down ATF6 in primary cultured neonatal rat atrial myocytes (NRAMs) using a chemical inhibitor of the proteolytic cleavage site enabling ATF6 activation and siRNA and measured ANP expression and secretion basally and in response to alpha- adrenergic agonist stimulation using phenylephrine. We also compared the ANP secretion from wild- type mice and ATF6 knockout mice in an ex vivo Langendorff model of the isolated perfused heart. Results: ATF6 knockdown in NRAMs significantly impaired basal and phenylephrine-stimulated ANP secretion. ATF6 knockout mice displayed lower levels of ANP in atrial tissue at baseline as well as after phenylephrine treatment. Similarly, in the ex vivo isolated perfused heart model, less ANP was detected in effluent of ATF6 knockout hearts compared to wild-type hearts. Conclusions: The ATF6 branch of the ER stress response is necessary for efficient co-secretional processing of pro-ANP to ANP and for agonist-stimulated ANP secretion from atrial myocytes. As ANP is secreted in a regulated manner in response to a stimulus and pro-ANP is synthesized and packaged through the classical secretory pathway, we posit that ATF6 is required for adequate expression, folding, trafficking, processing and secretion of biologically active ANP from the endocrine heart.

Na+/H+ Exchanger and Reperfusion-Induced Ventricular Arrhythmias in Isolated Perfused Heart: Possible Role of Amiloride

1993 ◽  
pp. 151-157
Author(s):  
Seibu Mochizuki ◽  
Shingo Seki ◽  
Masa-aki Ejima ◽  
Tatsuyuki Onodera ◽  
Masayuki Taniguchi ◽  
...  
Keyword(s):  
Ventricular Arrhythmias ◽  
Isolated Perfused Heart ◽  
Perfused Heart
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