Contrasting excitatory and inhibitory effects of adenosine in blood pressure regulation.
Administration of adenosine results in profound hypotension without the expected activation of reflex sympathetic and renin mechanisms in most animal models. This action can be explained by the vasodilatory and neuroinhibitory effects of adenosine. It is generally considered an inhibitory neuromodulator because it inhibits the release of virtually all neurotransmitters studied and produces hyperpolarization of neurons. In contrast, adenosine produces vasoconstriction of some vascular beds, including the renal and pulmonary circulations. Renal vasoconstriction is caused by activation of A1 receptors and involves an interaction with angiotensin II. In other vascular beds adenosine releases eicosanoids, including thromboxane, also resulting in vasoconstriction. Adenosine-induced vasoconstriction is transient and species dependent. Neither the receptor type, the molecular mechanisms of these actions, nor their significance to pathophysiological processes have been defined. Adenosine also has an apparent excitatory effect in the nucleus tractus solitarii. Microinjections of adenosine into this brain stem nucleus lead to decreased sympathetic tone and hypotension similar to those produced by the excitatory amino acid glutamate. The mechanism that explains this action has recently been explored and involves the release of glutamate by adenosine. Adenosine also stimulates afferent fibers mediating sympathetic activity, including renal and myocardial afferent nerves, and carotid and aortic chemoreceptors. Afferent nerve activation seems to be more pronounced in humans and may explain most of the cardiovascular and respiratory actions of adenosine in this species. Finally, animal studies suggest that endogenous adenosine plays a role in the regulation of the baroreceptor reflex and restrains the full expression of renin-dependent hypertension.
Biaggioni
I
I
Department of Medicine, Vanderbilt University, Nashville, Tenn. 37232.
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D001933:Brain Stem / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000209:etiology; D011983:Receptors, Purinergic / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
D011983:Receptors, Purinergic; D000241:Adenosine