A pharmacological analysis of the possible role of vasoactive mediators in compensatory coronary blood flow.

摘要: Although it is well established that the major determinant of coronary blood flow rate myocardial oxygen consumption (1–7), what couples this relationship between demand and supply remains ‘major unanswered question in physiology’ (7). In past, has been evaluated by examining under conditions when contractility (and hence demand) was increased cardiac pacing, exercise or after administration positive inotropic agents, such as catecholamines. The disadvantages these approaches are possible confounding effects reflexes arising from general circulation, release, particularly during exercise, substances contracting skeletal muscles can modify hemodynamics. There an alternative approach to study changes occur one branch a artery adjacent occluded. This involves, part, local demand. Such compensatory were first described several years ago both anesthetized (8–12) conscious (13–15) dogs. usual explanation for phenomenon results increase consequence enhanced region left ventricular wall supplied unoccluded vessel (6). believed compensate reduced contribution function area made ischemic. Using segmental shortening, we have recently shown (16,17) just preceeds flow. Further, there close shortening vessel. We suggested represent alternative, more local, basic supply. One possibility tight coupling vasodilator mediator released result leads corresponding appropriate Many suggestions identity mediator. These included adenosine (6,18,19), prostanoids (20–22), plasma kinins (23) nitric oxide (NO) (7,22,24). involvement ATP-dependent K+ (KATP) channels also (7,25–27). present study, began examining, using classical pharmacological approaches, role most likely single mediators. Moreover, because ‘it seems two chemicals operate simultaneously’ (28) should ‘move away concept coupler all seasons’ (5), examined mediators may be involved together. explored previously exercise-induced vasodilation (29,30). In therefore, describe inhibiting, means, production mediators, blocking their at receptor level, on increases circumflex anterior descending concentrated roles adenosine, bradykinin, NO, KATP channels, alone combination. Because noradrenaline early stages ischemia dilator large arteries (31), whether modified beta-adrenoceptor blockade.