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Gender related alterations of β‐adrenoceptor mechanisms in heart failure due to arteriovenous fistula
Author(s) -
Dent Melissa R.,
Tappia Paramjit S.,
Dhalla Naranjan S.
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.23058
Subject(s) - heart failure , arteriovenous fistula , medicine , cardiology , surgery
This study was undertaken to determine gender related changes in different components of β‐adrenoceptor (β‐AR) system in response to arteriovenous fistula (AV‐shunt), which is known to produce heart failure due to volume overload. AV‐shunt was induced in male and female rats for 16 weeks by the needle technique; ovariectomized (OVX) rats treated with or without estrogen were also used. Although AV‐shunt for 16 weeks produced cardiac hypertrophy in both sexes, male animals showed cardiac dysfunction whereas cardiac performance was maintained in females. Both β 1 ‐AR and β 2 ‐AR protein content and mRNA levels were decreased in male and increased in female hearts post‐AV‐shunt. The basal adenylyl cyclase (AC) activity was lower in the female heart; however, AC protein content and the increase in epinephrine (EPi)‐stimulated AC activity were greater in the female AV‐shunt group as compared to males. While AC V/VI and β‐arrestin 2 mRNA levels were decreased in males, mRNA level for GRK2 was increased in females post‐AV‐shunt. In contrast to intact females, AV‐shunt OVX animals showed depressed cardiac function, decreased β 1 ‐AR, β 2 ‐AR, and AC protein content, as well as reduced EPi‐stimulated AC activity. Treatment of OVX rats with 17‐β estradiol attenuated the AV‐shunt induced changes in β‐AR and AC protein content as well as cardiac dysfunction. These results reveal that β‐AR signal transduction system in response to AV‐shunt is downregulated in males and upregulated in females. Furthermore, estrogen appears to play an important role in the upregulation of β‐AR mechanisms and the maintenance of cardiac function in AV‐shunt females. J. Cell. Physiol. 227: 3080–3087, 2012. © 2011 Wiley Periodicals, Inc.