1998
DOI: 10.1172/jci1335
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Age-associated reductions in cardiac beta1- and beta2-adrenergic responses without changes in inhibitory G proteins or receptor kinases.

Abstract: While an age-associated diminution in myocardial contractile response to beta-adrenergic receptor (beta-AR) stimulation has been widely demonstrated to occur in the context of increased levels of plasma catecholamines, some critical mechanisms that govern beta-AR signaling must still be examined in aged hearts. Specifically, the contribution of beta-AR subtypes (beta1 versus beta2) to the overall reduction in contractile response with aging is unknown. Additionally, whether G protein-coupled receptor kinases (… Show more

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Cited by 193 publications
(140 citation statements)
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“…It has been suggested that the increase in MABP with age is a normal age-dependent process that may be a compensatory mechanism for loss of arterial compliance (4). Similarly, the decrease in HR is usually attributed to a diminution in the efficacy of ␤-adrenergic stimulation of the heart, which again is normal and an age-dependent process (41,43) The depressed MABP and HR in diabetic rats observed in the present study is in agreement with many other studies in STZ diabetic rats (9,14,18,20,23,31,39,44). Previous studies from our own laboratory have shown lower HR and reduced systolic blood pressure in conscious STZ-induced diabetic rats (44).…”
Section: Discussionmentioning
confidence: 99%
“…It has been suggested that the increase in MABP with age is a normal age-dependent process that may be a compensatory mechanism for loss of arterial compliance (4). Similarly, the decrease in HR is usually attributed to a diminution in the efficacy of ␤-adrenergic stimulation of the heart, which again is normal and an age-dependent process (41,43) The depressed MABP and HR in diabetic rats observed in the present study is in agreement with many other studies in STZ diabetic rats (9,14,18,20,23,31,39,44). Previous studies from our own laboratory have shown lower HR and reduced systolic blood pressure in conscious STZ-induced diabetic rats (44).…”
Section: Discussionmentioning
confidence: 99%
“…These results are similar to other reports on ␤AR density in Fisher 344 rat hearts (21, 38 -42), though Mader et al (43) did report a decrease in affinity. In other rat strains there may be moderate decreases in receptor number (6,19,25,44).…”
Section: Ptx-sensitive G Proteins In Left Ventricular Membranesmentioning
confidence: 99%
“…PTX ADP-ribosylates G␣ i /G␣ o and prevents their interaction with receptors, thereby removing the inhibition of AC by these G protein subtypes (46,47). Our previous studies have shown that PTX treatment of human atrial membranes results in an increase in AC stimulation through ␤ 2 AR and other G␣ s -coupled receptors (4), and others have shown that PTX treatment of myocytes increases ␤ 2 ARmediated contractility (2,6). As shown in Table II, the inactivation of G␣ i /G␣ o by PTX increases both basal and GPCRstimulated AC activity, and this effect is greater in the old than in the young left ventricular membranes for the G␣ i -coupled ␤ 2 ARs and glucagon receptors.…”
Section: Ptx Treatment Causes a Greater Increase In Ac Activity In Olmentioning
confidence: 99%
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