Permeability and model testing of heart capillaries by osmotic and optical methods

1980 ◽  
Vol 239 (4) ◽  
pp. H464-H464
Author(s):  
Fernando F. Vargas ◽  
Gertrude L. Blackshear ◽  
Randy J. Majerle

Rabbits were anesthetized with Nembutal; their hearts were removed and perfused with Ringers solution. Osmotic weight transients were then produced by test solute infusion into the perfusate. The rate constant for organ weight change was used to predict test solute venous concentration (Cv) and the distribution volume (V) during an osmotic transient by use of the Johnson and Wilson (6) model for capillary tissue exchange. By use of Cr EDTA, strongly purple in solution, we compared the above predictions with a value of Cv obtained directly by optical measurement of outflow venous concentration and values of V calculated from our measurements of organ weight and the known sucrose distribution volume. The close agreement between both sets of values with a permeability coefficient of 5 x 10-5 cm/s and a volume of distribution of 3.2 ml/10 g heart lead us to conclude that the model used closly represents the conditions of the isolated perfused heart, and that both the osmotic transient and the extraction measurements provide good estimates of organ capillary permeability.

1985 ◽  
Vol 12 (6) ◽  
pp. 573-576 ◽  
Author(s):  
B. V. Venkataraman ◽  
P. S. Shetty ◽  
Thangam Joseph ◽  
H. Mohamed Arifullah ◽  
P. M. Stephen

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Erik A Blackwood ◽  
Christopher C Glembotski

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.


1993 ◽  
pp. 151-157
Author(s):  
Seibu Mochizuki ◽  
Shingo Seki ◽  
Masa-aki Ejima ◽  
Tatsuyuki Onodera ◽  
Masayuki Taniguchi ◽  
...  

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