Adenosine inhibition of beta-adrenergic induced responses in aged hearts

1993 ◽  
Vol 265 (2) ◽  
pp. H494-H503 ◽  
Author(s):  
J. G. Dobson ◽  
R. A. Fenton

Because adenosine has an antiadrenergic action in the heart, young (3-4 mo) and aged (18-20 mo) adult Sprague-Dawley and Fischer 344 rat hearts were perfused to determine whether interstitial adenosine plays a role in the reduced metabolic and mechanical responsiveness of the aged heart to beta-adrenergic stimulation. Interstitial adenosine was approximately twofold greater in aged hearts compared with young adult hearts, and 10(-8) M isoproterenol (ISO) further increased these levels. ISO increased myocardial adenosine 3',5'-cyclic monophosphate content, glycogen phosphorylase activity, and cardiac contractility by 83, 150, and 130%, respectively, in young hearts but only increased these variables by 45, 74, and 61%, respectively, in aged hearts. Sulfophenyl-theophylline prevented the reduced ISO-induced responsiveness of the above variables in aged hearts. Exogenously administered adenosine deaminase eliminated the reduced ISO-induced contractile responsiveness in aged hearts. The apparent activities of 5'-nucleotidase and adenosine deaminase were not significantly different in ventricular samples from young and aged hearts. These results suggest that the elevated interstitial level of adenosine exerts a greater antiadrenergic effect in the aged heart, rendering it less responsive to beta-adrenergic stimulation. The increased interstitial level of adenosine in the aged heart does not appear to be due to a difference in the activities of either 5'-nucleotidase or adenosine deaminase.

1985 ◽  
Vol 248 (5) ◽  
pp. E560-E566
Author(s):  
A. Noguchi ◽  
P. A. Jett ◽  
A. H. Gold

Postnatal development of glycogen phosphorylase activation by the cAMP-independent pathway was examined in isolated rat hepatocytes from control and propylthiouracil-treated congenital hypothyroid rat pups. At 5 days postnatum there was complete phosphorylase activation by beta-adrenergic stimulation, glucagon, and the calcium ionophore A23187, but no activation by alpha-adrenergic stimulation. Activation of phosphorylase by angiotensin or vasopressin was less than in hepatocytes from adult rats (P less than 0.01). At 28 days postnatum activation by all of these hormones was complete. In the propylthiouracil-treated group hormone responsiveness was similar to the control at 5 days postnatum. However, alpha-adrenergic (P less than 0.025), angiotensin, and vasopressin (P less than 0.05) activation was decreased at 28 days postnatum, and beta-adrenergic, glucagon, and A23187 activation was complete. The attenuated responses were restored by thyroxine replacement from 15 days postnatum. [32P]Pi incorporation into phosphatidylinositol by epinephrine and vasopressin in 28-day propylthiouracil-treated rats was lower than the control (P less than 0.01). We speculate that the diminished phosphorylase response of hepatocytes to alpha-adrenergic, vasopressin, or angiotensin stimuli in the early neonatal period could be related to low receptor numbers and the weaker phosphoinositide response during this period. Also, the depressed phosphorylase response to alpha-adrenergic, vasopressin, and angiotensin stimulation in congenital hypothyroidism at 28 days postnatum could be related to a decrease in number of plasma membrane receptors for these agonists.


1998 ◽  
Vol 201 (4) ◽  
pp. 533-547 ◽  
Author(s):  
M Vornanen

A patch-clamp analysis of L-type Ca2+ current in ventricular myocytes of cold- and warm-acclimated rainbow trout (Oncorhynchus mykiss) and crucian carp (Carassius carassius) hearts was performed. Trout were acclimated at 4 and 17 degrees C and carp at 4 and 24 degrees C for a minimum of 4 weeks. Ventricular myocytes were isolated by enzymatic dissociation using collagenase and trypsin. Marked species-specific differences were noted in Ca2+ current density and its ss-adrenergic regulation. The density of basal Ca2+ current in crucian carp (6.9-7.4 pA pF-1) was almost double that of trout (4.2-4.5 pA pF-1) ventricular myocytes. Maximal beta-adrenergic stimulation increased Ca2+ current by approximately 2.3-fold in trout but by only 1.4-fold in crucian carp, so that Ca2+ current densities in the presence of 10 micromol l-1 isoprenaline were almost equal in trout (8.6-10.5 pA pF-1) and carp (9.6-10.4 pA pF-1) cardiac cells. Direct activation of adenylate cyclase by forskolin (10 micromol l-1) was also associated with similar interspecies differences in the stimulation of Ca2+ current. Thermal acclimation did not change either the density or the kinetics of L-type Ca2+ current in crucian carp ventricular myocytes. In trout cardiac cells, thermal acclimation had no effects on the density of Ca2+ current, but the rate of current inactivation was accelerated after acclimation to cold temperature. As a consequence of faster current decay, the contribution of sarcolemmal Ca2+ current to total cellular [Ca2+] was smaller in cold-acclimated than in warm-acclimated trout. The responses of Ca2+ current to maximal beta-adrenergic stimulation by isoprenaline or to direct activation of adenylate cyclase by forskolin were not changed by thermal acclimation in either species. It is concluded (1) that the density of sarcolemmal Ca2+ current is not increased after acclimation to cold, (2) that sarcolemmal Ca2+ influx through L-type Ca2+ channels can make a significant contribution to contractile [Ca2+] in both teleost species studied and (3) that ss-adrenergic stimulation of Ca2+ current is more important in modulating cardiac contractility in trout than in carp.


2010 ◽  
Vol 16 (9) ◽  
pp. S171
Author(s):  
Daiji Miura ◽  
Kazufumi Nakamura ◽  
Wakako Yoshikawa ◽  
Ken Hashimoto ◽  
Noriyuki Kataoka ◽  
...  

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