Phasic release of adenosine during steady state metabolic stimulation in the isolated guinea pig heart.

Abstract

If adenosine is the major factor responsible for myocardial metabolic vasodilation, its release should be sustained as long as oxygen consumption and coronary flow are augmented. To see if adenosine meets this criterion, we examined the time course of its release during norepinephrine infusion in isolated, non-working guinea pig hearts (n = 8). During an 11-minute infusion period (steady state perfusate concentration = 6 X 10(-8) M), the coronary effluent was collected over 30-second intervals for measurements of coronary flow (ml/min per g), and adenosine and inosine release (pmol/min per g). Myocardial oxygen consumption (MVO2 = microliter O2/min per g) was measured at 1, 4, 6.5, and 11 minutes. Control values of coronary flow, myocardial oxygen consumption, and adenosine and inosine release were 7.5 +/- 0.4, 85 +/- 5, 22 +/- 5, and 431 +/- 39, respectively. During norepinephrine infusion, coronary flow, myocardial oxygen consumption, and adenosine release attained maximal levels within one minute (inosine within 2 minutes). These values were 10.6 +/- 0.4, 125 +/- 9, 849 +/- 110, and 2595 +/- 581, respectively. Thereafter, coronary flow and myocardial oxygen consumption values were sustained. In contrast, adenosine and inosine release significantly declined to nadirs by 9.5 minutes. Thereafter, steady state levels were maintained at 117 +/- 24 and 960 +/- 294, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine and Cardioprotection in the Diseased Heart

“…The underlying mechanism for this phenomenon may be different from that of adenosine release when -adrenoceptors are stimulated. 59 We have also found that 2-adrenergic activity modifies the vasodilatory action of adenosine (Fig 3); a low dose of the 2-adrenoceptor agonist clonidine enhances adenosineinduced coronary vasodilation, [60][61][62] and low doses of yohimbine and rauwolscine, 2-adrenoceptor antagonists, reduce the coronary flow response to either endogenous or exogenous adenosine. [59][60][61] This is consistent with the earlier studies of Nayler et al 63 They observed that phenoxybenzamine, a non-specific -adrenoceptor antagonist, blocks the vasodilatory action of adenosine in isolated rat and guinea pig hearts.…”

“…59 We have also found that 2-adrenergic activity modifies the vasodilatory action of adenosine (Fig 3); a low dose of the 2-adrenoceptor agonist clonidine enhances adenosineinduced coronary vasodilation, [60][61][62] and low doses of yohimbine and rauwolscine, 2-adrenoceptor antagonists, reduce the coronary flow response to either endogenous or exogenous adenosine. [59][60][61] This is consistent with the earlier studies of Nayler et al 63 They observed that phenoxybenzamine, a non-specific -adrenoceptor antagonist, blocks the vasodilatory action of adenosine in isolated rat and guinea pig hearts. [60][61][62] Furthermore, the reduction in ischemiainduced myocardial damage by administration of clonidine in coronary hypoperfusion and in coronary microembolization strongly suggests that adenosine plays an important role in the dilation of the coronary arterial bed; clonidine significantly increased coronary blood flow in both of the ischemic models without augmentation of adenosine release.…”

Tissue acidosis: role in sustained arteriolar dilatation distal to a coronary stenosis.

“…Although other mediators may substitute for low pH or elevated Pco2, results of earlier studies conducted in our laboratory indicate that sustained elevation of interstitial fluid adenosine concentration19 or increased prostacyclin production32 also are not essential for long-term maintenance of reduced arteriolar tone distal to a severe coronary arterial stenosis. Thus, the results of the present investigation are best understood in the context of a series of experiments, [16][17][18][19]31,32 which indicate that known mediators of acute changes in coronary arteriolar tone may not have an important role (either alone or in combination) in the long-term maintenance of reduced arteriolar tone distal to a severe coronary arterial stenosis. The mechanism(s) involved in maintenance of reduced coronary arteriolar tone in this setting is unknown but could involve alterations in one or more proteins responsible for regulation of vascular smooth muscle contraction and relaxation.…”

Regulation of adenosine formation by the heart.

“…Such a mechanism would explain an interesting coincidence. When the isolated rodent heart is stimulated, both glycolysis (Neely and Morgan, 1974) and adenosine release (DeWitt et al, 1983) exhibit an early peak and then fall to a steady state level which is greater than control. This could be because they are both influenced by signals related to the phosphorylation potential.…”