The regional distribution of adenosine-regulating enzymes in the left and right ventricle walls of control and hypertrophic heart

Abstract

The transmural distribution of the adenosine-generating enzyme 5'-nucleotidase (5'N) and of the adenosine-degrading enzymes adenosine deaminase (ADA), AMP deaminase (AMP-D) and adenosine kinase (Ado-K) were determined across the walls of left and right ventricles of control and hypertrophic rat hearts. The enzyme distribution across the left ventricle wall (but not across the right wall) of normal hearts was not uniform: 5'N activity shows its highest levels in the subepicardial and in the subendocardial regions, whereas all the other enzyme activities show their lowest levels. A similar pattern of transmural distribution was also detected in other mammalian species (ox and pig). In the experimental cardiac hypertrophy, caused by two different types of chronic cardiac overload, the levels and the profiles of transmural distribution of 5'N and ADA enzyme activities may significantly change across the rat left ventricle wall.

Transmural distribution of extracellular purines in isolated guinea pig heart.

“…In general there were no differences noted in subendocardial versus subepicardial 5'-nucleotidase activities. In all three species examined, the ratio of 5'-nucleotidase/adenosine deaminase was significantly greater in the epicardial layers than in the mid-myocardium (11). Thus, the processes responsible for net adenosine formation are greatest in the epicardial and endocardial layers and lowest in the mid-myocardium.…”

“…Under basal conditions, endocardial blood flow is thought to be slightly higher than or equal to the epicardial blood flow (10,21). Owing to a variety of factors, including greater wall stresses and intramyocardial pressure (7,8), and enhanced endocardial metabolism (9,10,22,23), subendocardial oxygen consumption is -1.5-fold greater than subepicardial oxygen consumption under normal conditions (5,6,10). Since tissue pressure during systole is so much greater in the subendocardium than in the subepicardium, endocardial coronary flow is largely restricted to diastole (7,8).…”

“…These include regional differences in 02 supply/demand and intracellular metabolism (7)(8)(9)(10) and an uneven transmural distribution of the enzymes regulating adenosine formation and/or degradation. A recent examination of the regional distribution of adenosine-regulating enzymes (5'-nucleotidase and adenosine deaminase) in rat, ox, and pig heart demonstrated that only in the ox heart was there a tendency for greater 5'-nucleotidase and lower adenosine deaminase activity in the endocardium relative to the epicardium (11). Even in this species the transmural difference was minimal.…”

“…Furthermore, these same indices only reflect global changes in adenosine levels and cannot detect regional differences in extracellular adenosine. The mammalian myocardium is a heterogeneous tissue and the subepicardial and subendocardial regions differ physically, metabolically, and functionally (5)(6)(7)(8)(9)(10). Little information is available regarding spatial heterogeneities in extracellular metabolite levels.…”

“…Little information is available regarding spatial heterogeneities in extracellular metabolite levels. Interestingly, recent studies indicate that transmural differences exist in the distribution of adenosine-regulating enzymes (11) and it has been demonstrated that transmural gradients exist for intracellular adenosine during control perfusion and ischemia in vivo (12). Thus, it is possible that physiological messengers such as adenosine may be unevenly distributed throughout the myocardial interstitial space.…”