Activation of purinergic receptor subtypes in the nucleus tractus solitarius elicits specific regional vascular...

The nucleus tractus solitarius (NTS) is a major integrative site in the brain stem involved in central autonomic control. Several lines of evidence indicate that ATP, acting at P2x purinoceptors, and adenosine, acting at A2a adenosine (P1) purinoceptors, play synchronous roles as transmitter substances in NTS-mediated mechanisms of cardiovascular control. The purpose of this study was to examine regional vascular response patterns elicited by selective activation of purinergic receptor subtypes in the NTS. Adult male rats were anesthetized with a mixture of alpha-chloralose and urethane. Pulsed-Doppler flow probes were placed on the iliac, renal and superior mesenteric arteries via a midline laparotomy for measurement of regional blood flow velocities. The animal was then mounted prone in a stereotaxic unit and the dorsal surface of the medulla was surgically exposed in the region of the obex. Microinjections of alpha, beta-methylene ATP (alpha,beta-MeATP), a selective P2x purinergic receptor agonist, or 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680), a selective A2a adenosine (P1) receptor agonist, were made into the subpostremal region of the NTS via multibarrel glass micropipettes. Both alpha,beta-MeATP (25 and 100 pmoles/rat) and CGS 21680 (2 and 20 pmoles/rat) produced significant dose-related reductions in blood pressure and heart rate. These agonist-elicited depressor response patterns were associated with a pronounced and preferential dilation of the iliac vascular bed. However, alpha, beta-MeATP, but not CGS 21680, also caused significant dilation of the renal and superior mesenteric vascular beds, although lesser in magnitude compared to the iliac bed, whereas the hypotensive actions of CGS 21680 were considerably more prolonged compared to the very rapid and transient effects of alpha,beta-MeATP. These results support the view that extracellular ATP and adenosine via synchronous actions at specific purinergic receptor subtypes in the NTS may be functionally linked as neural signalling substances to selectively coordinate the regulation of regional vasomotor tone.